Cancer chemotherapy has been the most common cancer treatment. However, it has side effects that kill both tumor cells and immune cells, which can ravage the patient’s immune system. Chemotherapy should be administered depending on the patient’s immunity as well as the level of cancer cells. Thus, we need to design an efficient treatment protocol. In this work, we study a feedback control problem of tumor-immune system to design an optimal chemotherapy strategy. For this, (...) we first propose a mathematical model of tumor-immune interactions and conduct stability analysis of two equilibria. Next, the feedback control is found by solving the Hamilton–Jacobi–Bellman equation. Here, we use an upwind finite-difference method for a numerical approximate solution of the HJB equation. Numerical simulations show that the feedback control can help determine the treatment protocol of chemotherapy for tumor and immune cells depending on the side effects. (shrink)

Most models of patient-physician communication take decision-making as a central concept. However, we found that often the treatment course of metastatic cancer patients is not easy to describe in straightforward terms used in decision-making models but is instead frequently more erratic. Our aim was to analyse these processes as trajectories. We used a longitudinal case study of 13 patients with metastatic colorectal and pancreatic cancer for whom palliative chemotherapy was a treatment option, and analysed 65 semi-structured interviews. (...) We analysed three characteristics of the treatment course that contributed to the ‘erraticness’ of the course: (1) The treatment (with or without chemotherapy) contained many options; (2) these options were not stable entities to be decided upon, but changed identity over the course of treatment, and (3) contrary to the closure (option X means no option Y, Z, etc.) a decision implies, the treatment course was a continuous process in which options instead remained open. When the treatment course is characterised by these many and changeable options that do not result in closure, the shared decision-making model should take these into account. More attention needs to be paid to the erratic character of the process in which the doctor has to provide continuous information that is related to the changing situation of the patient; also, flexibility in dealing with protocols is warranted, as is vigilance about the overall direction of the process. (shrink)

Major problems in cancer chemotherapy are toxicity, resistance, and cancer heterogeneity. A new theranostic paradigm has been proposed by the authors. Many million small molecules (SM) are bound to the proteins extracted from a patient's cancer. SM that also bind proteins extracted from normal human tissues are subtracted from the cancer protein bound SM leaving a large array of SM targeting many sites on each of the cancer biomarkers. Targeting many more than the conventional (...) 1 – 4 cancer biomarkers will reduce development of tumor resistance. After several cycles of selection and counter selection, DNA codes appended to the SM will be PCR amplified to provide templates for restricted libraries of the SM to improve selectivity and sensitivity. The large array of selected and counter selected SM assures that many of the compounds in the array will penetrate the cell membrane and bind to intracellular targets, low tumor resistance, low background for imaging, low therapeutic toxicity, and targeting of the diverse biomarkers present in the heterogeneous mixture of cells in primary and metastatic cancer. Theranostic use of radiolabeled SM binding many sites on many, not necessarily critical, biomarkers provides high cancer cell killing. Experiments to provide proof of principle of this novel concept suggested by the authors. -/- . (shrink)

BackgroundPrevious findings indicated that breast cancer patients often have dysfunction in empathy and other cognitive functions during or after chemotherapy. However, the manifestations and possible neuro-electrophysiological mechanisms of pain empathy impairment in breast cancer patients after chemotherapy were still unknown.ObjectiveThe current study aimed to investigate the potential correlations between pain empathy impairment and event-related potentials in breast cancer patients undergoing chemotherapy.MethodsTwenty-two breast cancer patients were evaluated on a neuropsychological test and pain empathy paradigm (...) before and after chemotherapy, containing the Chinese version of the Interpersonal Reactivity Index, while recording ERP data.ResultsThe empathic concern scores were lower and personal distress scores were higher on IRI-C task compared with those before chemotherapy. Meanwhile, the accuracy rates were lower than those before chemotherapy for both pain and laterality tasks on the pain empathy paradigm. However, the response time was no significant differences before and after chemotherapy. Further, the amplitude of the N1 component was significantly increased, and the amplitude of the P2 component was significantly decreased in the subsequent ERP study. A linear mixed effect model was used to analyze the correlation, the average amplitude of N1 and P2 were positively correlated with the accuracy rates in laterality tasks.ConclusionThe results indicated that pain empathy impairment was performed in chemotherapeutic breast cancer patients, which was possibly correlated to the changes of N1 and P2 components in ERP. These findings provide neuro-electrophysiological information about chemo-brain in breast cancer patients. (shrink)

ObjectivesWomen who underwent chemotherapy for metastatic breast cancer used both adaptive and maladaptive coping strategies but had low implementation levels. The present study explores the qualitative experience of coping strategies for women with MBC undergoing CT in Beijing.MethodsA hermeneutic phenomenological approach was employed on twenty Chinese MBC women undergoing CT. These interviews were transcribed verbatim, coded using thematic analysis, and analyzed using NVivo 11.ResultsThree themes are highlighted: Maintaining hope; Spiritual growth, and Self-perceived support resources.ConclusionThe present study results have (...) led to a greater understanding of the tremendous impact of CT on MBC women’s lives. This research provides insight into the scope of maintaining hope. Spiritual growth and self-perceived support resources were crucial factors to coping strategies among MBC women to improve their quality of life.Clinical RelevanceBy attaining the adaptive coping strategies and further understanding about Chinese MBC women, health care professionals are encouraged to appraise MBC women’s specific problems and adopt effective interventions to improve MBC women’s psychosocial wellbeing. (shrink)

The aim of this study is to provide a feedback control, called the Chemotherapy Protocol Law, with the purpose to keep the density of tumor cells that are treated by chemotherapy below a “tolerance level” L_c, while retaining the density of normal cells above a “healthy level” N_c. The mathematical model is a controlled dynamical system involving three nonlinear differential equations, based on a Gompertzian law of cell growth. By evoking viability and set-valued theories, we derive sufficient conditions (...) for the existence of a Chemotherapy Protocol Law. Thereafter, on a suitable viability domain, we build a multifunction whose selections are the required Chemotherapy Protocol Laws. Finally, we propose a design of selection that generates a Chemotherapy Protocol Law. (shrink)

The DNA in human cells is continuously undergoing damage as consequences of both endogenous processes and exposure to exogenous agents. The resulting structural changes can be repaired by a number of systems that function to preserve genome integrity. Most pathways are multicomponent, involving incision in the damaged DNA strand and resynthesis using the undamaged strand as a template. In contrast, O6-alkylguanine-DNA alkyltransferase is able to act as a single protein that reverses specific types of alkylation damage simply by removing the (...) offending alkyl group, which becomes covalently attached to the protein and inactivates it. The types of damage that ATase repairs are potentially toxic, mutagenic, recombinogenic and clastogenic. They are generated by certain classes of carcinogenic and chemotherapeutic alkylating agents. There is consequently a great deal of interest in this repair system in relation to both carcinogenesis and cancer chemotherapy. BioEssays 24:255–266, 2002. © 2002 Wiley Periodicals, Inc.; DOI 10.1002/bies.10063. (shrink)

A prematurely menopausal woman who underwent chemotherapy for breast cancer wants to have a child with her husband with help from an infertility clinic. Two doctors discuss the risks involved for the couple.

In lieu of an abstract, here is a brief excerpt of the content:Bringing Cancer Care to Those who Don't Have ItLawrence N. ShulmanI have been treating cancer patients in the Harvard Medical School hospitals since 1977, and in those 35 years we have made tremendous progress. Though work still needs to be done, and far too many patients still die of cancer, many are cured. In particular, children and young adults have a high rate of cure from (...) such diseases as Hodgkin's lymphoma, non-Hodgkin's lymphoma, acute lymphoblastic leukemia, and childhood sarcoma. Patients with breast cancer in the US have a greater than 80% chance for long-term survival. The death rate from cervical cancer in the US is very low. These results have been achieved by making diagnoses earlier, in many cases surgical excision, and often systemic therapies such as chemotherapy, hormonal therapy, radiation therapy, and more recently by using so-called "targeted" therapies—those directed at particular molecular characteristics of the cancer cells.Princess Dina Mired has said that the opportunity to survive cancer should not be an accident of geography. In cases where we already have effective and inexpensive tools to cure cancer, these treatments should be considered a basic human right, a life-saving medical service.I met Patty, a young woman living in the U.S. during November of her senior year in high school, after she discovered a small lump above her left collar bone. Though she felt entirely well, she called her primary care doctor who saw her the next day, felt the enlarged lymph node, and referred her to a surgeon, who did a biopsy later that week. Her primary care doctor also called me, and we scheduled a visit when the pathology results were available. The following week the pathologist notified Patty's pediatrician that the biopsy showed Hodgkin's lymphoma. When I met Patty, she was a bright and focused young woman, waiting to hear about her college applications and enjoying her senior year. Her cancer diagnosis was completely out of context with her life as she planned it, but with the support of her family and boyfriend, she seemed prepared to take things one step at a time. A PET CT scan demonstrated a modest mass in the mediastinum (chest), but no other disease. She was in an early stage of the disease with an excellent prognosis. We recommended and administered six months of chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine—four chemotherapy agents that are off-patent, and relatively inexpensive. She lost her hair, not a trivial issue for her, but otherwise felt reasonably well during the treatment. She was determined to graduate with her classmates, and was able continue to attend school and keep up with her work. In June, seven months into her cancer diagnosis and treatment, she graduated with honors, and was on track to enroll in college in September.Like other 18-year-old women with Hodgkin's lymphoma, Patty had an over 80% chance for cure with the potential for a long and productive life ahead of her because we could perform a biopsy, make a diagnosis, and safely and effectively treat her with four inexpensive, off-patent, chemotherapy drugs. She had nearly the same likelihood of living a long and fruitful life as her classmates, and had the same chances for childbearing. In my line of work, with the knowledge we now possess, to allow someone like Patty to die without a chance of curative care is simply unacceptable. Treatment of curable cancers should be considered on par with the right to clean water, adequate nutrition, treatment for infectious disease, and access to maternal and child healthcare services.But in many places in the world, people with cancers we could easily eradicate in Boston have no access to cancer services, and do die unnecessarily. The local healthcare infrastructure has no [End Page E10] capacity to evaluate a patient, perform or process a biopsy, make a diagnosis, or treat the patient with potentially curative surgery, chemotherapy and radiation. I have rounded on the wards of hospitals in developing countries, stopping to talk with numerous patients like Patty: young women, some of whom might have had Hodgkin's lymphoma, but no... (shrink)

Research suggests that the experience of cancer is diverse rather than homogeneous. The strong emotions and stress associated with cancer lead to a search for coping strategies. Men with different types of cancer utilise physical, psychological, interpersonal, and spiritual strategies. Despite the research, the specific adaptation and coping strategies used by men with testicular cancer have rarely been studied. We focused on the adaptation and coping strategies of newly diagnosed patients (n = 17) with testicular (...) class='Hi'>cancer in Slovakia. For this purpose, we conducted a longitudinal qualitative study based on semi-structured interviews before, during and after chemotherapy. The verbatim transcribed interviews were analysed using ideal type analysis with a focus on typology formation and trajectory analysis in narrative approaches. The main types of psychological adaptation and strategies were grouped into 4 trajectories: the psychological barrier between the self and the illness as a coping mechanism; realistic optimism; meaning-making; and the complicated process of adaptation. The differences in adaptation were related to the patients’ emotional state before the disease, previous unprocessed life events, a death in the family during treatment, but also to the metastatic nature of the disease or the recurrence of testicular cancer. These results can help healthcare providers identify those at higher risk for complicated adaptation. (shrink)

Chemotherapy is one of the most common treatments used in cancer therapy despite its serious side effects, which remain a huge concern. To the most common side effects include memory and concentration problems as well as changes in taste. This paper presents a very preliminary study focusing on cognitive dysfunction after chemotherapy in breast cancer. This phenomenon, called Cancer-Related Cognitive Dysfunction, is a frequent occurrence. The obtained results prove the impact of chemotherapy on the (...) participant’s ability to concentrate. The QEEG method and digital data analysis were used as the measurement methods. (shrink)

Plasminogen activator inhibitor‐1 (PAI‐1) is a physiological inhibitor of urokinase (uPA), a serine protease known to promote cell migration and invasion. Intuitively, increased levels of PAI‐1 should be beneficial in downregulating uPA activity, particularly in cancer. By contrast, in vivo, increased levels of PAI‐1 are associated with a poor prognosis in breast cancer. This phenomenon is termed the “PAI‐1 paradox”. Many factors are responsible for the upregulation of PAI‐1 in the tumor microenvironment. We hypothesize that there is a (...) breast cancer predisposition to a more aggressive stage when PAI‐1 is upregulated as a consequence of Metabolic Syndrome (MetS). MetS exerts a detrimental effect on the breast tumor microenvironment that supports cancer invasion. People with MetS have an increased risk of coronary heart disease, stroke, peripheral vascular disease and hyperinsulinemia. Recently, MetS has also been identified as a risk factor for breast cancer. We hypothesize the existence of the “PAI‐1 cycle”. Sustained by MetS, adipocytokines alter PAI‐1 expression to promote angiogenesis, tumor‐cell migration and procoagulant microparticle formation from endothelial cells, which generates thrombin and further propagates PAI‐1 synthesis. All of these factors culminate in a chemotherapy‐resistant breast tumor microenvironment. The PAI‐1 cycle may partly explain the PAI‐1 paradox. In this hypothesis paper, we will discuss further how MetS upregulates PAI‐1 and how an increased level of PAI‐1 can be linked to a poor prognosis. BioEssays 29:1029–1038, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Feminist Studies 41, no. 3. © 2015 by Feminist Studies, Inc. 571 Moving through Cancer: An Interview with Carol Collins Artist Carol Collins spoke with Feminist Studies editorial collective member Stephanie Gilmore about her experience of cancer, treatment, and recovery and how it gave rise to an art series that examines what nature means in the midst of unnatural treatments. SG: Carol, thank you for the opportunity (...) to speak with you about your artwork. Having just lost my sister to cancer, your work reminds me of much pain and loss, but also of love and the desire to survive. Before we discuss the work itself, I would like to hear about your journey through cancer, treatment, and recovery. CC: The breast cancer patient’s journey is complex and perilous. When I was healthy, I was ignorant about the magnitude of suffering many cancer patients undergo. And, although I am a private person, I’m now publicly sharing my cancer experience in order to be a voice for those who have suffered through similar treatments—and worse—and those who sadly are no longer with us to tell their story. Being bald and nauseated are not the most awful possible side effects of the treatments, although they are the most well known. Some women survive the cancer but can die from the treatments, or others suffer through the treatments and die anyway. Often, it seems many believe patients can overcome their 572 Carol Collins adversity solely with positive thinking and persistence. However, not discussing the array of physical and psychological damage that even those with good prognoses incur propagates ignorance about this malady. I hope that my artwork and story will promote a deeper understanding of a breast cancer patient’s plight and will encourage more support for research for individualized therapies and prevention. My cancer journey began when I received a breast cancer diagnosis in January 2014. Life just before that point was good; the future was bright. Tendon pain, caused by my flat feet and a lot of exercising, was my only known ailment. But one day a routine mammogram revealed three tumors in my right breast. The radiology oncologist said the masses were highly likely to be cancerous, so he immediately did painful core biopsies at the sites of my three tumors. The next day, it became clear that we needed to act quickly. The biopsy results revealed I had a very aggressive invasive breast cancer with estrogen, progesterone, and HER2 receptors. Breast cancer in premenopausal women grows quickly due to the high level of hormones present. The oncologists and surgeons said I would, at a minimum, need a mastectomy and possibly lymph node resection, and they warned that I would likely need chemotherapy, which would destroy my eggs and ovaries. After learning of my limited options, I approved the removal of one breast and my sterilization. I knew I needed to think rationally and face the giant raven before me head on. However, I did not realize the magnitude and multitude of physical and psychological pains, illnesses, and losses that were soon to come. The first year of cancer treatments inflicted much physical pain. I received three extremely painful injections into my right breast with a radiolabeled colloid just prior to the mastectomy. The pain came from the injected dye, not from the needle. The modified radical mastectomy was more excruciatingly painful than I anticipated, even with painkillers and overnight hospitalization. Breast reconstruction was an option that added more pain and discomfort from weekly fillings of the installed “expander” and additional surgeries. Extreme pain after the mastectomy prevented me from lying down for months. Foolishly, I did not get an injection port installed in my chest. Instead, I endured numerous deep (and often unsuccessful) needle pricks into the seemingly few veins of my left arm (which still had its lymph nodes) that were appropriate for infusions over the period of a year. Shooting pains across my chest and arm were the norm. Carol Collins 573 In addition to the surgically induced physical pain, the chemotherapy quickly caused a myriad of undesirable physical side effects. It is scary to realize that the medical community does not often fully understand... (shrink)

Advances in the understanding of Ras oncoprotein function suggest novel points for anti‐tumor intervention. First, upstream‐acting guanine nucleotide exchange factors and SH2/SH3 domain‐containing adaptor proteins that link Ras with growth factor receptor tyrosine kinases have recently been characterized. Second, work on downstream‐acting Ras effector functions including the Ras GTPase‐activating protein (p120GAP) and the Raf kinase has revealed direct biochemical interactions that are functionally required for oncogenic Ras signalling. We summarize progress in these areas and discuss the potential for novel applications (...) to anti‐cancer chemotherapy. (shrink)

ObjectivesWorking-age cancer patients face barriers to resuming work after treatment completion. Those resuming work contend with reduced productivity arising from persisting residual symptoms. Existing studies of return to work after cancer diagnosis were done predominantly in Western countries. Given that employment and RTW in cancer survivors likely vary regionally due to healthcare provision and social security differences, we documented rates and correlates of RTW, work productivity, and activity impairment among Chinese cancer survivors in Hong Kong at (...) one-year post-treatment.MethodsOf 1,106 cancer patients assessed at six-months post-cancer treatment, 593 previously worked; detailed work status, psychological distress, physical symptom distress, supportive care needs, health-related quality of life, and illness perception were assessed. Six months later, work productivity and activity impairment were assessed. Descriptive analyses examined RTW rate. Fully adjusted regressions determined RTW, work productivity, and activity impairment predictors.ResultsAt baseline, 39% were working, 26% on sick leave, and 35% were unemployed. Compared to patients returning to work, unemployed participants were older, likely manual/service-oriented workers, and had lower family income, chemotherapy, fewer unmet health system and information needs, poorer physical functioning, and negative illness perceptions. Sick leave participants were likely service-oriented workers, who had head and neck cancer, chemotherapy, and poor physical functioning. At FU, baseline depressive symptoms, physical symptom distress, and negative illness perceptions predicted presenteeism and work productivity loss; gynecological cancer, fewer unmet health system and information needs, and greater unmet sexuality needs predicted absenteeism; physical symptom distress, negative illness perception, and poor physical functioning predicted activity impairment.ConclusionCancer survivors who had more physically demanding jobs and poorer physical functioning delayed RTW. Unmanaged physical symptom and psychological distress hindered work productivity. (shrink)

Although chemotherapy is one of the most common treatments for cancer, it can be only partially successful. Drug resistance is the main cause of the failure of chemotherapy. In this work, we present a mathematical model to study the impact of both intrinsic and acquired resistances on chemotherapy effectiveness. Our simulations show that intrinsic resistance could be as dangerous as acquired resistance. In particular, our simulations suggest that tumors composed by even a small fraction of intrinsically (...) resistant cells may lead to an unsuccessful therapy very quickly. Our results emphasize the importance of monitoring both intrinsic and acquired resistances during treatment in order to succeed and the importance of doing more experimental and genetic research in order to develop a pretreatment clinical test to avoid intrinsic resistance. (shrink)

Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain‐of‐function mutations, in general, (...) has been productive. However, it has been a major challenge to use standard pharmacologic approaches to target loss‐of‐function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics. (shrink)

Myc‐driven tumorigenesis involves a non‐transcriptional role for Myc in over‐activating replicative Cdc45‐MCM‐GINS (CMG) helicases. Excessive stimulation of CMG helicases by Myc mismanages CMG function by diminishing the number of reserve CMGs necessary for fidelity of DNA replication and recovery from replicative stresses. One potential outcome of these events is the creation of DNA damage that alters genomic structure/function, thereby acting as a driver for tumorigenesis and tumor heterogeneity. Intriguingly, another potential outcome of this Myc‐induced CMG helicase over‐activation is the creation (...) of a vulnerability in cancer whereby tumor cells specifically lack enough unused reserve CMG helicases to recover from fork‐stalling drugs commonly used in chemotherapy. This review provides molecular and clinical support for this provocative hypothesis that excessive activation of CMG helicases by Myc may not only drive tumorigenesis, but also confer an exploitable “reserve CMG helicase vulnerability” that supports developing innovative CMG‐focused therapeutic approaches for cancer management. (shrink)

In this essay, I propose that DNA‐binding anti‐cancer drugs work more via chromatin disruption than DNA damage. Success of long‐awaited drugs targeting cancer‐specific drivers is limited by the heterogeneity of tumors. Therefore, chemotherapy acting via universal targets (e.g., DNA) is still the mainstream treatment for cancer. Nevertheless, the problem with targeting DNA is insufficient efficacy due to high toxicity. I propose that this problem stems from the presumption that DNA damage is critical for the anti‐cancer (...) activity of these drugs. DNA in cells exists as chromatin, and many DNA‐targeting drugs alter chromatin structure by destabilizing nucleosomes and inducing histone eviction from chromatin. This effect has been largely ignored because DNA damage is seen as the major reason for anti‐cancer activity. I discuss how DNA‐binding molecules destabilize chromatin, why this effect is more toxic to tumoral than normal cells, and why cells die as a result of chromatin destabilization. (shrink)

BackgroundFear of cancer recurrence is an important cause of suffering for cancer survivors, and both empirical evidence and theoretical models suggest that prognostic uncertainty plays a causal role in its development. However, the relationship between prognostic uncertainty and FCR is incompletely understood.ObjectiveTo explore the relationship between prognostic uncertainty and FCR among patients with ovarian cancer.DesignA qualitative study was conducted utilizing individual in-depth interviews with a convenience sample of patients with epithelial ovarian cancer who had completed first-line (...) treatment with surgery and/or chemotherapy. Semi-structured interviews explored participants’ understanding of their prognosis; experiences, preferences, and attitudes regarding prognostic information; and strategies for coping with prognostic uncertainty. Inductive qualitative analysis and line-by-line software-assisted coding of interview transcripts was conducted to identify key themes and generate theoretical insights on the relationship between prognostic uncertainty and FCR.ResultsThe study sample consisted of 21 participants, nearly all of whom reported experiencing significant FCR, which they traced to an awareness of the possibility of a bad outcome. Some participants valued and pursued prognostic information as a means of coping with this awareness, suggesting that prognostic uncertainty causes FCR. However, most participants acknowledged fundamental limits to both the certainty and value of prognostic information, and engaged in various strategies aimed not at reducing but constructing and maintaining prognostic uncertainty as a means of sustaining hope in the possibility of a good outcome. Participants’ comments suggested that prognostic uncertainty, fear, and hope are connected by complex, bi-directional causal pathways mediated by processes that allow patients to cope with, construct, and maintain their uncertainty. A provisional dual-process theoretical model was developed to capture these pathways.ConclusionAmong patients with OC, prognostic uncertainty is both a cause and an effect of FCR—a fear-inducing stimulus and a hope-sustaining response constructed and maintained through various strategies. More work is needed to elucidate the relationships between prognostic uncertainty, fear, and hope, to validate and refine our theoretical model, and to develop interventions to help patients with OC and other serious illnesses to achieve an optimal balance between these states. (shrink)

Childhood cancer incidence is rising, affecting a growing proportion of elementary school students. For most of these children, school attendance can be limited by hospitalisations, treatments and side effects. However, little is yet known about the educational needs and experiences of this population. This phenomenological study explored the school experiences of 10 6- to 12-year-old children with cancer as they underwent chemotherapy. Results revealed perceptions that attending school in the hospital or home during cancer treatment is (...) essentially lonely, confusing and “different”. These perceptions intertwined to illuminate five themes: school should involve fun activities; group educational formats are preferable; old school is the “best school”; being a “good student” is important during treatment; and attending school is complicated during treatment. Therefore, hospital-based and homebound schooling programmes should integrate socially interactive and cognitively engaging curriculum to best support the learning needs of this population. (shrink)

Background:Women's health has received renewed attention in the last few years including health rehabilitation options for women affected by breast cancer. Dancing has often been regarded as one attractive option for supporting women's well-being and health, but research with women recovering from breast cancer is still in its infancy. Dancing with Health is multi-site pilot study that aimed to evaluate a dance programme for women in recovery from breast cancer across five European countries.Methods:A standardized 32 h dance (...) protocol introduced a range of Latin American dances presented within a sports and exercise framework with influences from dance movement therapy. Fifty-four women (M age 53.51; SD 7.99) participated in the study who had a breast cancer diagnosis 6 weeks, no indication of metastasis, or scheduled surgery/chemotherapy/radiation treatment for the duration of the intervention. Primary outcome data was collected for anthropometric and fitness measures next to cancer-related quality of life.T-tests and Wilcoxon signed ranked tests were used to establish differences pre and post intervention. Cohen's d was also calculated to determine the effect size of the intervention.Results:Statistically significant changes were found for: (i) weight, right and left forearm circumference and hip; (ii) 6 min walking, right and left handgrip, sit-to-stand and sit-and-reach; (iii) the EORTC-QLQ C30 summary score as well as the subscales of emotional and social functioning and symptoms. In all cases the direction of change was positive, while Cohen's d calculated showed that the effect of the intervention for these parameters ranged from intermediate to large.Conclusion:Changes on the above anthropometric, fitness and quality of life measures suggest that the intervention was of value to the participating women recovering from breast cancer. Results also advocate collaborative efforts across countries to further research. (shrink)

Chemotherapy is an important therapeutic approach for cancer treatment. However, drug resistance is an obstacle that often impairs the successful use of chemotherapies. Therefore, overcoming drug resistance would lead to better therapeutic outcomes for cancer patients. Recently, studies by our own and other groups have demonstrated that there is an intimate correlation between the loss of the F‐box and WD repeat domain‐containing 7 (FBW7) tumor suppressor and the incurring drug resistance. While loss of FBW7 sensitizes cancer (...) cells to certain drugs, FBW7‐/‐ cells are more resistant to other types of chemotherapies. FBW7 exerts its tumor suppressor function by promoting the degradation of various oncoproteins that regulate many cellular processes, including cell cycle progression, cellular metabolism, differentiation, and apoptosis. Since loss of the FBW7 tumor suppressor is linked to drug resistance, FBW7 may represent a novel therapeutic target to increase drug sensitivity of cancer cells to conventional chemotherapeutics. This paper thus focuses on the new functional aspects of FBW7 in drug resistance. (shrink)

Shortages of generic, injectable chemotherapeutics have been increasing in prevalence since 2006. Due to the lack of access to first-line, lifesaving treatments, physicians have been forced to ration chemotherapy between patients. Although the scarcity has been managed with good intentions, it has been done in an ad hoc manner, without the benefit of an ethically grounded and standardized schema. Using an approach based on the “accountability for reasonableness” method by Daniel and Sabin, I establish a framework and protocol for (...) rationing that is specific to chemotherapy. Prior to the state of true shortage, I present guidelines for the use of an adequate supply of chemotherapy with knowledge of upcoming scarcity. Within the rationing framework itself, I first prioritize emergency use of chemotherapeutics and those already receiving treatment at the time of shortage. I advocate for stratifying patients based on the prognostic indicators of their cancer type, using a combination of clinical-trial-based initial response and longer term survival, followed by the patients’ line of treatment. All patients who are not able to receive their “best” treatment must receive a sequent, next-best treatment, and their treatment team must have the ability to appeal to a rationing committee in special circumstances. I reject the ideas of stratification based on the intention of the treatment, perceived quality of life, pre-existing condition not impacting performance status, the classical “sickest first” argument, and giving preference to pediatric cases. Lastly, I advocate for any system of rationing to be transparent to those it affects and acknowledge the difficulties it presents to patients and physicians alike. (shrink)

We examined if cancer patients' health-related quality of life (HRQoL) scores on the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 are affected by the specific time point, before or during treatment, at which the questionnaire is completed, and whether this could bias the overall treatment comparison analyses. A 'completion-time window' variable was created on three closed EORTC randomised control trials in lung (non-small cell lung cancer, NSCLC) and colorectal cancer (CRC) to indicate when (...) the QLQ-30 was completed relative to chemotherapy cycle dates, defined as 'before', 'on' and 'after'. HRQoL mean scores were calculated using a linear mixed model. Statistically significant differences (P < 0.05) were observed on 6 and 5 scales for 'on' and 'after' comparisons in the NSCLC and two-group CRC trial, respectively. As for the three-group CRC trial, several statistical differences were observed in the 'before' to 'on' and the 'on' to 'after' comparisons. For all three trials, including the 'completion-time window' variable in the model resulted in a better fit, but no substantial changes in the treatment effects were noted. We showed that considering the exact timing of completion within specified windows resulted in statistical and potentially clinically significant differences, but it did not alter the conclusions of treatment comparison in these studies. (shrink)

Over the past decades, anti-cancer treatments have evolved rapidly from cytotoxic chemotherapies to targeted therapies including oral targeted medications and injectable immunooncology and cell therapies. New anti-cancer medications come to markets at increasingly high prices, and health insurance coverage is crucial for patient access to these therapies. State laws are intended to facilitate insurance coverage of anti-cancer therapies.Using Massachusetts as a case study, we identified five current cancer coverage state laws and interviewed experts on their perceptions (...) of the relevance of the laws and how well they meet the current needs of cancer care given rapid changes in therapies. Interviewees emphasized that cancer therapies, as compared to many other therapeutic areas, are unique because insurance legislation targets their coverage. They identified the oral chemotherapy parity law as contributing to increasing treatment costs in commercial insurance. For commercial insurers, coverage mandates combined with the realities of new cancer medications — including high prices and often limited evidence of efficacy at approval — compound a difficult situation. Respondents recommended policy approaches to address this challenging coverage environment, including the implementation of closed formularies, the use of cost-effectiveness studies to guide coverage decisions, and the application of value-based pricing concepts. Given the evolution of cancer therapeutics, it may be time to evaluate the benefits and challenges of cancer coverage mandates. (shrink)

Objectives: Fatigue is a frequent debilitating symptom associated with cancer. However, scientific data on cancer-related fatigue is scarce in developing nations. This work examines psychometric properties of the multidimensional fatigue inventory and analyzes the level of fatigue among Ethiopian patients with cancer in comparison with data from Germany.Methods: A sample of 256 patients with cancer drawn from a hospital in Ethiopia was examined with the MFI-20 and the European Organization for Research and Treatment of Cancer (...) Quality of Life questionnaire. A comparative sample of 780 German patients with cancer served as the control.Results: The MFI-20 scales and total score showed acceptable reliability with a considerable convergent validity between MFI-20 and the EORTC QLQ-C30 fatigue scale. The Ethiopian patients with cancer reported higher levels of fatigue than the German patients. Analyses of variance showed that Ethiopian patients with cancer who were illiterate, having advanced cancer, and those who did not receive either surgery or chemotherapy reported especially high levels of fatigue.Conclusion: The MFI-20 is a fairly reliable and valid instrument to be used with Amharic speaking patients with cancer. The high level of fatigue in these patients implies that appropriate cancer care is needed in developing countries. (shrink)

IntroductionWe aimed to study post-traumatic stress disorder symptoms in breast cancer patients during the coronavirus disease pandemic.Materials and methodsWe included BC patients receiving medical treatment during the first COVID-19 lockdown in France. PTSD symptoms were evaluated using the Impact of Event Scale-Revised questionnaire. Quality of life [Functional Assessment of Cancer Therapy-General ], cognitive complaints [Functional Assessment of Cancer Therapy–Cognitive Function ], insomnia [Insomnia Severity Index ], and psychosocial experiences during lockdown were also evaluated. Multivariable logistic regression was (...) used to identify clinical factors and psychosocial factors associated with PTSD symptoms.ResultsAmong the 253 included BC patients, 46% had metastatic cancer and 52% were treated by chemotherapy alone. COVID-19-induced adjustments in medical oncology practices were experienced by 27% of patients. No case of COVID-19 was reported; 23% of BC patients had PTSD symptoms. Compared to other patients, patients with PTSD symptoms had more fears relative to COVID-19 infection, had more feeling of isolation, and had more prescription or increased use of psychotropic drugs. In the multivariable model adjusted for clinical factors, fears relative to COVID-19 and increased use of psychotropic drugs were independently associated with PTSD symptoms. Besides, patients with PTSD symptoms had poor quality of life, and more cognitive complaints and insomnia.ConclusionPost-traumatic stress disorder symptoms were observed in 23% of BC patients during the first COVID-19 lockdown in France. Psychological supports are needed for patients treated during the COVID-19 pandemic. (shrink)

Topoisomerase enzymes – found in prokaryotes to human cells – control conformational changes in DNA and aid the orderly progression of DNA replication, gene transcription and the separation of daughter chromosomes at cell division. Several classes of anti‐cancer drugs are now recognised as topoisomerase poisons because of their ability to trap topoisomerase molecules on DNA as ‘cleavable complexes’. Understanding how drugs generate such complexes and why they are toxic to actively growing cancer cells is a major challenge for (...) the development of modern approaches to chemotherapy. (shrink)

Angiogenesis plays an essential role in tumor growth, invasion and metastasis. After initial pessimism about the usefulness of the antiangiogenic therapeutic approach for cancer, interest has increased in the development of antiangiogenic compounds after the first clinical approval of an antiangiogenic therapy. The anti‐vascular endothelial growth factor (VEGF) antibody bevacizumab has recently been approved for use in combination with chemotherapy for the treatment of metastatic colorectal and non‐small cell lung cancer patients. However, no survival benefit has been (...) demonstrated in anti‐VEGF monotherapy trials, probably due to the high complexity of tumor angiogenesis regulation. Experimental and clinical data, including the approval of the multitargeted drugs sunitinib and sorafenib, indicate that exciting results, including tumor regression, can be expected from the combined targeting of different pathways in the tumor angiogenesis scenario. Several obstacles, including the high cost of new molecular targeted drugs make this therapeutic approach difficult. BioEssays 29:1159–1168, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Rationale Treatment guidelines recommend a more conservative surgical approach than mastectomy for early stage breast cancer and a stronger emphasis on adjuvant therapy. Registry data at South Australian teaching hospitals have been used to monitor survivals and treatment in relation to these guidelines.Aims and objectives To use registry data to: (1) investigate trends in survival and treatment; and (2) compare treatment with guidelines.Methods Registry data from three teaching hospitals were used to analyse trends in primary courses of treatment of (...) breast cancers during 1977–2003 (n = 4671), using univariate analyses and multiple logistic regression. Disease-specific survivals were analysed using Kaplan–Meier product limit estimates and multivariable Cox proportional hazards regression.Results The 5-year survival was 79.9%, but with a secular increase, reaching 83.6% in 1997–2003. The relative risk of death (95% confidence limits) was 0.74 (0.62, 0.88) for 1997–2003, compared with previous diagnoses, after adjusting for tumour node metastasis stage, grade, age and place of residence. Treatment changes included an increase in conservative surgery (as opposed to mastectomy) from 51.7% in 1977–1990 to 76.8% in 1997–2003 for stage I (P < 0.001) and from 31.1% to 52.2% across these periods for stage II (P < 0.001). Adjuvant radiotherapy also became more common (P < 0.001), with 20.6% of patients receiving this treatment in 1977–1990 compared with 60.7% in 1997–2003. Radiotherapy generally was more prevalent when conservative surgery was provided, although also relatively common in mastectomy patients when tumour diameters exceeded 50 mm or when there were four or more involved nodes. The proportion of patients receiving chemotherapy increased (P < 0.001), from 19.6% in 1977–1990 to 36.9% in 1997–2003, and the proportion having hormone therapy also increased (P < 0.001), from 34.3% to 59.4% between these periods.Conclusions Survivals appear to be increasing and treatment trends are broadly consistent with guideline directions, and the earlier research on which these recommendations were based. (shrink)

In humans, the intestine is the major reservoir of microbes. Although the intestinal microbial community exists in a state of homeostasis called eubiosis, environmental and genetics factors can lead to microbial perturbation or dysbiosis, a state associated with various pathologies including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Dysbiotic microbiota is thought to contribute to the initiation and progression of CRC. At the opposite end of the spectrum, two recently published studies inSciencereveal that the microbiota is essential for (...) chemotherapeutic drug efficacy, suggesting a beneficial microbial function in cancer management. The dichotomy between the beneficial and detrimental roles of the microbiota during cancer initiation, progression, and treatment emphasize the interwoven relationship between bacteria and cancer. Moreover, these findings suggest that the microbiota could be considered as a therapeutic target, not only at the level of cancer prevention, but also during management, i.e. by enhancing the efficacy of chemotherapeutics. (shrink)

This pilot study explores the reasons patients have for refusing chemotherapy, and the ways oncologists respond to them. Our hypothesis, generated from interviews with patients and oncologists, is that an ethical approach that views a refusal as an autonomous choice, in which patients are informed about the pros and cons of treatment and have to decide by weighing them, is not sufficient. A different ethical approach is needed to deal with the various evaluations that play a role in treatment (...) refusal. If patients forgo further treatment, while curative or palliative methods are available, there is no perspective from which to integrate the weighing of pros and cons of treatment and the preferences and values of individual cancer patients. A discrepancy thus results as regards what “good reasons” are, evoking misunderstandings or even breaking off communication. Suggestions are given for follow up research. (shrink)

ObjectiveBreast cancer may profoundly affect a couple’s sex life. The present study examines whether patient-, partner- and relationship-related characteristics are associated with sexual activity of couples following breast cancer diagnosis in the treatment phase and over time.MethodsWomen with breast cancer and their male cohabiting partners participated in a longitudinal study in Denmark. Logistic regression was used to examine associations of patient-, partner- and relationship-related characteristics at baseline with couples’ sexual activity at baseline, 5 and 12 months later. (...) The longitudinal analyses were stratified for couples’ sexual activity status at baseline.ResultsA total of 722, 533 and 471 couples were included in the analyses at baseline, 5- and 12-months follow-up, respectively. Older age, depressive symptoms and lower vitality of patients were associated with lower odds of couples’ sexual activity at baseline; chemotherapy treatment and older age of patients were associated with lower odds at 5-months follow-up in couples who were not sexually active at baseline. Higher ratings of emotional closeness, affectionate behavior and satisfaction with dyadic coping were associated with higher odds for sexual activity at baseline and over time in couples who were sexually active at baseline.ConclusionSexual counseling during cancer treatment and rehabilitation should include a couple perspective. Relationship-related variables may be a protective factor for remaining sexually active after breast cancer diagnosis. Interventions could focus on strengthening these factors. Health professionals also need to consider the patients’ breast cancer treatment, vitality, and emotional distress in counselling on sexuality. (shrink)

Tumors are often viewed as unique entities with specific behaviors. However, tumors are a mixture of differentially evolved subpopulations of cells in constant Darwinian evolution, selecting the fittest clone and allowing it to outgrow the rest. As in the natural environment, the niche defines the properties the fittest clones must possess. Therefore, there can be multiple fit clones because of the various microenvironments inside a single tumor. Hypoxia is considered to be a major feature of the tumor microenvironment and is (...) a potential contributor to the cancer stem cell (CSC) phenotype and its enhanced tumorigenicity. The acidic microenvironment around hypoxic cells is accompanied by the activation of a subset of proteases that contribute to metastasis. Because of aberrant angiogenesis and the inaccessibility of their locations, hypoxic cells are less likely to accumulate therapeutic concentrations of chemotherapeutics that can lead to therapeutic resistance. Therefore, the targeting of the hypoxic CSC niche in combination with chemotherapy may provide a promising strategy for eradicating CSCs. In this review, we examine the cancer stem cell hypothesis and its relationship to the microenvironment, specifically to hypoxia and the subsequent metabolic switch and how they shape tumor behavior. (shrink)

On December 20, 2002, the Ohio Supreme Court issued an opinion in Dardinger v. Anthem Blue Cross & Blue Shield granting a landmark punitive damages award against the defendant-insurer for breach of contract and bad faith in its coverage of a cancer patient. The court directed that the punitive damages award of $30 million, should it be accepted by the plaintiff, be apportioned between the plaintiff and a cancer research fund to be established in the name of the (...) plaintiff's deceased wife, Esther Dardinger. In so doing, the court broke new ground in the scope and social purpose of punitive damages in health care litigation, as well as the courts’ role in distributing those damages.After being diagnosed with metastatic brain tumors in October 1996, Esther began intra-arterial chemotherapy treatments at the recommendation of her physician, Dr. Newton. IAC is a targeted form of chemotherapy in which an arterial catheter is threaded through a cranial artery near the tumor and into the brain. (shrink)

The attitudes of women patients with cancer were explored when they were invited to participate in one of three randomised trials that included chemotherapy at two university centres and a satellite centre. Fourteen patients participating in and 15 patients declining trials were interviewed. Analysis was based on the constant comparative method. Most patients voiced positive attitudes towards clinical research, believing that trials are necessary for further medical development, and most spontaneously argued that participation is a moral obligation. Most (...) trial decliners, however, described a radical change in focus as they faced the actual personal choice. Almost no one got an impression of clinical equipoise between treatments in the trials, and most patients expressed discomfort with randomisation. A patient’s choice to participate was mainly determined by whether the primary focus was on treatment effect or on adverse effects. Both knowledge about and feelings towards trials originated mostly from the media, although paradoxically the media were largely seen as untrustworthy. Mistrust was shown towards the pharmaceutical industry, and although most patients originally trusted that doctors primarily pursued the interest of patients, they did not trust the adequacy of doctors or industry in maintaining self-regulation. Thus, public control measures were judged to be essential. (shrink)

In line with some recent studies that emphasize the importance of embodied meanings in social interaction and face-to-face communication, this study recognizes the significance of the body in human meaning-making processes and contributes to the emerging studies that explore the relation of the body, self, and social interaction. Unlike studies that analyze the body as a symbol or text disconnected from the actual body (i.e., a representation), this study does not separate appearance from the body. Rather, this research explores embodied (...) appearance and shows how a nonconforming appearance might highlight the body's presence in interaction, making it a focal point of attention in contrast to the taken-for-grantedness of our bodies in everyday life. I examine the reported experiences of some breast cancer survivors to find the implications of changes in physical appearance due to radiation, chemotherapy, or surgery, for survivors and their interactions with others. (shrink)

This article aims to identify and describe the ethical dilemmas that are involved in the care of patients with incurable cancer. The data were collected in semistructured focused interviews with 32 patients, 13 nurses and 13 doctors from two central hospitals and four community health centres. The interviews were tape-recorded and transcribed verbatim. Interpretation was based on the method of content analysis. Ethical dilemmas occurred at the time of diagnosis, in connection with telling the truth, in providing information, in (...) the treatment of pain, and in decision-making situations concerning active treatment. Dilemmas of active treatment concerned chemotherapy, intravenous infusions, blood transfusions and antibiotics. There were also problems in relationships between nursing staff and next of kin, as well as a lack of co-operation between nurses and doctors. (shrink)

IntroductionThe aim of the present study is to carry out a multidimensional analysis on the relation between satisfaction with social support received, resilience and optimism in cancer patients and their quality of life.Materials and MethodsData were gathered through questionnaires fulfilled by 142 cancer patients. Data relate to sociodemographic, health, quality of life, social support, resilience and optimism.ResultsSatisfaction with the sources and types of support, resilience and optimism relates positively with quality of life. Predictive models show that informational support (...) from friends is the variable that most increases patients’ general health, while emotional support from the partner is the one that best improves how patients cope with the disease. In the same line, emotional support from the partner, together with informational support from family are the ones that most contribute to reduce patients’ symptoms. Resilience improves general health and functioning, and reduces symptoms. Patients’ optimism and resilience also reduce symptoms. Gender differences were found, with females showing lower quality of life than males, mainly in how they cope with cancer. Patients in the stage of treatment showed lower quality of life and higher symptoms. Such increase was observed in patients who received hormonotherapy or chemotherapy.DiscussionImportant practical implications can be drawn from results, which could help improve cancer patients’ quality of life through intervention strategies aimed at increasing their resilience, optimism and the social support provided by their closer sources. (shrink)

As a university professor, an environmentalist, and a world-traveller, Sue Hendler was thriving. Then she was diagnosed with metastatic breast cancer. She had to give up her job, make hard decisions about medical treatment, and drastically shorten her vision of the future. As her cancer spread, she ironically acquired a new identity as a cancer "survivor." Compelled to find meaning in her "new normal" of life with a fatal disease, she decided to write for a wider audience. (...) In Dying in Public: Living with Metastatic Breast Cancer, Hendler talks about her experiences of undergoing surgery, taking steroids, receiving chemotherapy, and enrolling in a clinical drug trial. As her condition worsens she remains committed to living fully. She struggles with writing a bucket list, discusses her "legacy," and talks about her feelings of anger and the importance of love. She also describes how she lived, towards the end, with the support of the members of her "Care Team," a group of over thirty friends, family, and health care workers who enabled her to remain at home until the day before her death. This honest, witty, and unsentimental depiction of "dying in public" is a profound tribute to a life well lived. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Ice Cream for BreakfastMichelle MethvenIn June of 2011, on a warm sunny day in Toronto, Canada, my partner and I brought our daughter Stella into the local hospital emergency room for what we believed would be a routine check–up. She had been exhibiting worsening clumsiness and limping for the previous two weeks and we thought it would be easier just to get her seen and have whatever it was (...) dealt with rather than wait two months to see a specialist. My partner and I believed it was likely a severe ear infection, or maybe Lyme disease from a recent camping trip. We each called our workplaces and said we would be an hour or so late. Nothing could have prepared us for the news 22 hours after arriving at the hospital, that Stella had a cancerous mass in her brain. After a biopsy three days later to confirm the diagnosis, Stella was diagnosed with Diffuse Intrinsic Pontine Glioma (DIPG), and given less than a year to live.Parents most often describe DIPG as “a monster.” The tumour saturates the pons and shuts down nerve pathways one at a time. In no particular order, and in no particular time, sufferers (most often young children) lose the ability to walk, sit up, hold up their head, speak and see. The pons is also responsible for breathing, swallowing and regulating the heartbeat, so death can come in many forms at any given time. Though it destroys the brain’s ability to command, the person continues to think and understand as the main part of the brain is untouched. Different from most cancers, chemotherapy and radiation have almost no effect on DIPG; even trials with the most toxic chemotherapies do not slow its progress.My partner and I were shaken to the core at this diagnosis. Looking at our energetic, redheaded [End Page 31] mop–topped little imp, it was impossible to fathom that she had just been given a fatal diagnosis. Yet we knew the doctors at the hospital were among the best and most sought–after in the world, so denial was never a part of our mantra.A week after Stella was diagnosed, we met with a neuro–oncologist to discuss our plans. The only treatment that is slightly effective for DIPG is focal radiation, which can stall the tumor’s growth, granting what is known as a “honeymoon period” of no new symptoms. The honeymoon lasts approximately six months, but there are no guarantees. Twenty percent of children get no honeymoon whatsoever after radiation, and others get only weeks. The doctor we met with confirmed radiation would not be curative, but would “buy time”. He explained that radiation involved six weeks of treatment, seven days a week. Following the six weeks of treatment, there would be a period of anywhere from one to six months in which Stella would likely be asymptomatic. However, at some point, the symptoms generally return and when they do, children deteriorate relatively quickly. Sometimes it takes a month or two, but on occasion there is as little as two weeks between progression and death.As Stella’s parents, we were not convinced that the prescribed radiation was something we wanted to subject Stella to. Because she was only two, and a very spirited and energetic child, it would have been virtually impossible to have her lie quietly on the table in hospital each day for six weeks while radiation was put behind her ear. The neuro–oncologists’ solution was that Stella be sedated for each daily radiation treatment, which would make her groggy for a big part of the day and necessitate needles and IV. As parents, we were presented with an impossible gamble. Do we risk taking away six weeks of her still somewhat symptom–free life for a possible extra three to six months later? And the timing was difficult as well. It was late June. If we chose to radiate it would mean spending the entire summer shuttling her between hospital and home with no weeks at the cottage, and much less time to attend neighbourhood BBQ’s, parties, trips to the park, the library, science centre and zoo... (shrink)

It's common knowledge that published medical findings tell only part of the story, the other part consisting of unpublished records of negative trials, sometimes of the same agents. No one, of course, knows precisely how much lies below the waterline, but informed estimates suggest that as many as half of all trials undertaken remain unreported —a percentage sufficient to cast a shadow over the entire corpus of published medical research. The effect is incalculable. That negative findings of trials of (...) class='Hi'>cancer chemotherapies would be withheld from publication seems inconceivable, but a paper documented that practice, and its slanting effect on the published literature, some 30 years ago.... (shrink)