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Doxorubicin is a widely used antineoplastic agent that may cause irreversible dilated cardiomyopathy. Doxorubicin-induced cardiomyopathy (DIC) can occur several years after exposure and carries a poor prognosis. Although cardiac resynchronization therapy (CRT) is a useful intervention in end-stage heart failure unresponsive to optimal medical therapies, its efficacy in DIC remains unknown. Four consecutive patients receiving CRT for DIC were evaluated before and after CRT. CRT resulted in improvements in the mean left ventricular ejection fraction at 1 month from 21+/-4.7% to 34+/-5% (p=0.03) and at 6 months (to 46+/-7.5%, p=0.01). CRT-induced reverse remodeling was observed, with a mean reduction in left ventricular internal diameter at end-diastole from 54.75+/-3.7 to 52.5+/-1.9 mm at 1 month (p=0.06) and further to 47+/-2.3 mm at 6 months (p=0.03). All patients experienced reductions in heart failure symptoms and improvements in New York Heart Association functional class (p<0.05). The impact of CRT was sustained over a follow-up of 18.5+/-3.5 months. In conclusion, this study suggests that patients with DIC, refractory to optimal pharmacologic therapy and meeting criteria for resynchronization device implantation, may achieve sustained benefit from CRT.

Purpose: There has been interest in using biomarkers that aid the evaluation of new anticancer agents. We evaluated trends in the use of biomarkers and their contribution to the main goals of phase I trials., Experimental Design: We did a systematic review of abstracts submitted to the American Society of Clinical Oncology annual meeting from 1991 to 2002 and the publications related to these abstracts. We analyzed the use of biomarkers and their contribution to published phase I trials., Results: Twenty percent of American Society of Clinical Oncology phase I abstracts (503 of 2458) from 1991 to 2002 included biomarkers. This proportion increased over time (14% in 1991 compared with 26% in 2002; P < 0.02). Independent predictors of the use of biomarkers included National Cancer Institute sponsorship, submission in the time period of 1999 to 2002, adult population, and drug family (biological agents). Biomarkers supported dose selection for phase II studies in 11 of 87 of the trials (13%) emanating from these abstracts. However, the primary determinants of phase II dose and schedule were toxicity and/or efficacy in all but one of these 87 trials (1%). Biomarker studies provided evidence supporting the proposed mechanism of action in 34 of 87 of the published trials (39%)., Conclusions: The use of biomarkers in phase I trials has increased over the period from 1991 to 2002. To date, biomarker utilization has made a limited and primarily supportive contribution to dose selection, the primary end point of phase I studies. Additional studies are needed to determine what type of biomarker information is most valuable to evaluate in phase I trials.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient and support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. The evolving field of oncology increasingly requires a team of medical specialists working in unison to deliver optimal medical care. While this coordination may maximize the technical synergy of care, it can challenge interprofessional and interdisciplinary connections. Poor and miscommunication and conflicts between staff and between the family and providers adversely affect patient care and quality of life. Furthermore, lack of communication leaves a vacuum that sucks in fear. A recent Newsweek article highlighted the challenges of practicing in the age of high-tech medicine. The author had to beg for a prognosis for her critically ill and dying husband, with unhelpful subspecialists failing to communicate the bigger picture. This article explores the tough issue of how teams handle uncertainty and bad news and how patients and families can be better supported in the multifaceted paradigm of modern care.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to patients and support to caregivers while encouraging the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum in which caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Increasingly, cancer patients are subjected to advertisements related to oncologic therapies and other cancer-related products in the popular media. Such direct-to-consumer advertising is controversial: while it may inform, educate, and perhaps even empower patients, it also has the ability to misinform patients, and strain their relationships with oncology providers. The U.S. Food and Drug Administration requires that direct-to-consumer advertising provide a balanced presentation of a product's benefits, risks, and side effects, but this can be difficult to achieve. Through a discussion of this topic by an oncology fellow, ethicist, cancer survivor, and senior oncologist, the role of direct-to-consumer advertising and its often subtle effects on clinical practice in oncology are explored. Although sparse, the medical literature on this increasingly prevalent type of medical communication is also reviewed.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH) founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient and support to caregivers and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. The diagnosis of cancer is incredibly stressful, and treatments are arduous. Humor may help to ease the pain, show the human side of the health care team, and help everyone cope. Whether the patient uses humor to lighten the mood of a difficult consultation with their physician, or health care workers use it to help cheer each other through the day, humor and laughter can be valuable tools. Humor can soften the isolation experienced by both patients and staff. When used sensitively, respecting the gravity of the situation, humor can build the connection among the caregiver, patient, and family. However, insensitive joking is offensive and distressing, and experience suggests a variable acceptance of humor by patients with life-threatening illnesses, making humor a high-risk strategy, and it can be a pejorative maker of an adversive power differential. The medical literature contains little on humor, and very little research has been conducted on this common aspect of human communication. Through an examination of physician and nurse experiences, the role of humor in medicine is reviewed.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital, founded The Kenneth B. Schwartz Center. The Schwartz Center is a nonprofit organization dedicated to advancing compassionate health care delivery, with the goal of providing hope to patients and support to caregivers. The Schwartz Center Rounds is a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, families, and caregivers, and gain insight and support from fellow staff members. The case is presented of a patient with a precipitous decline in health due to rapidly progressive, metastatic non-small cell lung cancer. The discussion at Schwartz Center Rounds centers on oncologists' feelings of failure and coping mechanisms when dealing with patients' deaths. This discussion is followed by a first-year oncology fellow's reaction to caring for this and other terminally ill patients. Then, to provide a broader framework in which to understand these issues, the emotional cost and measurable benefit of close relationships with patients is investigated. To conclude, further educational initiatives are advocated to assist both physicians-in-training and more senior clinicians in dealing with the difficult issues that arise when caring for very ill and dying patients.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH) founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient and support to caregivers and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. For many, cancer is synonymous with death. Fearing death is a rational response. For too long, medicine has ignored this primeval fear. Increasingly, clinicians recognize and address end-of-life issues, facing patients' and our own emotional vulnerabilities in order to connect and explore problems and fears. Listening and learning from the patient guides us as we acknowledge much of the mystery that still surrounds the dying process. Rarely is there a simple or right answer. An empathetic response to suffering patients is the best support. Support is vital in fostering the adjustment of patients. A silent presence may prove more helpful than well-meant counsel for many patients. Through an examination of eight caregiver narratives of their patients' experiences, the role of the health care provider in the dying process, particularly in regard to challenging fear, is reviewed.

Context: In the past, cancer patients entering phase 1 studies confronted the prospects of high risk and unlikely benefit. Over the last decade, cancer drugs under development have become more targeted, and the clinical research environment has become more scrutinized. The impact of these changes on the risks and benefits to patients who participate in phase 1 cancer trials is unknown., Objective: To determine trends in the rates of treatment-related (toxic) death, objective response, and serious toxicity and to identify factors associated with these outcomes., Data Sources: We searched abstracts and journal articles reporting the results of phase 1 cancer treatment trials originally submitted to annual meetings of the American Society of Clinical Oncology (ASCO) from 1991 through 2002., Study Selection: We focused on published single-agent trials that enrolled patients with advanced solid tumors and excluded studies testing agents already approved by the US Food and Drug Administration at the time of the ASCO presentation., Data Extraction: Multiple observers independently extracted information on trial design, location, sponsorship, types of tumors treated, drug class, route of administration, and clinical outcomes., Data Synthesis: The overall toxic death rate for 213 studies (involving 6474 cancer patients) published in peer-reviewed journals was 0.54%, while the overall objective response rate was 3.8%. Toxic death rates decreased over the study period, from 1.1% over the first 4 years of the study (1991-1994) to 0.06% over the most recent 4-year period (1999-2002) (P<.01). Response rates also decreased but by proportionally much less. After adjusting for characteristics of the experimental trials and the investigational agents, the odds of a patient dying from an experimental treatment while participating in a trial submitted during the most recent 4-year period were less than one tenth those of a patient participating in a trial submitted during the first 4-year period (odds ratio, 0.09; 95% confidence interval, 0.01-0.67; P = .009). In comparison, the adjusted odds of a patient experiencing an objective response over the same time periods decreased by approximately half (odds ratio, 0.46; 95% confidence interval, 0.32-0.66; P<.001)., Conclusions: The level of risk experienced by cancer patients who participate in phase 1 treatment trials appears to have improved over the 12-year period from 1991 through 2002. Because toxic death rates have decreased more quickly than have objective response rates, the ratio of risk to benefit may have also improved. These changes relate in part to the targeted and less-toxic nature of newer cancer drugs and are coincident with the increased attention that has been paid to the safety of clinical research over the time period we analyzed.

The causes of interpatient variation in severe toxicity resulting from treatment with weekly 5-fluorouracil (5-FU)/ leucovorin (LV) are poorly understood. This study was undertaken to examine the contribution of commonly occurring polymorphisms in the dihydropyrimidine dehydrogenase (DPYD) gene to interpatient variability in 5-FU pharmacokinetics and toxicity. Patients with stage III/IV colorectal cancer were treated by bolus intravenous (I.V.) injection with 500 mg/m2 doses of 5-FU and LV once every week. The pharmacokinetics of 5-FU was determined on weeks 1 and 4. Genotyping assays were developed for 8 polymorphisms in the DPYD gene. A well-characterized functional polymorphism in the 5' untranslated region of the thymidylate synthase (TS) gene was also analyzed. A cohort of 22 patients (15 male, 7 female) with a median age of 61 years was evaluated. Although there was no relationship between the area under the plasma concentration time curve (AUC) for the first dose of 5-FU and worst-grade toxicity during the first cycle of therapy, 3 of the 4 patients in whom the AUC on week 4 was more than equal to 5 microgram/h/mL greater than the value for the first dose experienced grade 3/4 toxicity during subsequent treatment. Among the 8 polymorphisms in the DPYD gene, 7 were found to vary in the study population but none were significantly associated with the AUC of 5-FU. There was no relationship between the DPYD and TS genotypes examined and 5-FU toxicity. Extensive polymorphism in the DPYD gene was observed; however, no conclusive correlations existed between the DPYD and TS genotype and 5-FU pharmacokinetics or toxicity. Decreases in 5-FU clearance in certain patients may provide insight into the increased toxicity following repetitive cycles of treatment with weekly I.V. bolus 5-FU. The present study offers useful themes for undertaking larger prospective pharmacogenetic studies in the future.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Three invited patients attended rounds and told their compelling stories; these each effectively demonstrated their fight as cancer survivors. Much of the strength that they displayed came from the different types of support they each received, and the invaluable role of the medical team. Each shared a very positive experience with 'The Wellness Community,' in Boston. The article discusses issues of support and the role of formal support groups. Types of support intervention, the impact they have on quality of life and survival are reviewed.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient and support to caregivers and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Metaphors illuminate complex issues and can paint a thousand words. However, fundamental to individual and collective expression, they are also capable of creating or perpetuating stereotypes, and stigma. In oncology, the military metaphor is perhaps the most prominent, with the high profile of the "War on Cancer," and the imperative for patients to have a fighting spirit. Balancing the instinct to fight with words of healing and acceptance remains a challenge. The history of the military metaphor and how the humanities have illuminated cancer as a metaphor are reviewed. The advantages and disadvantages of the use of this metaphor are discussed, as well as the use of other metaphors in the psychosocial dynamic of care.

Purpose: To review characteristics of contemporary phase III oncology trials and create an explicit framework to help clinical researchers prioritize novel therapies for phase III testing., Methods: We searched the MEDLINE and EMBASE databases for all reviews of phase III trials; cataloged all phase III trials in two national clinical trial databases; and reviewed approval criteria of recently approved oncology drugs from public data provided by the US Food and Drug Administration. Industry data not available elsewhere in the medical literature were obtained from a sourcebook published by a large contract research organization., Results: Phase III oncology trials are the most expensive and time-consuming aspect of the drug development process. The results of these trials continue to exert the greatest influence on the treatment decision of oncologists and remain pivotal to the granting of drug approval. Making optimal decisions about which agents to advance to phase III testing may decrease the overall cost of cancer drug development and limit the number of patients exposed to ineffective drugs. A conceptual decision model for prioritizing novel therapies for phase III testing is presented., Conclusion: Cancer drug development has become more complex and expensive, whereas overall clinical progress remains slow. The transition from phase II to phase III requires a strategic decision that is based on new considerations. A greater investment in phase I and II drug trials may be required to provide the information necessary for phase III planning.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded the Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient and support to caregivers and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum during which caregivers discuss a specific cancer patient, reflect on the important psychological issues faced by patients, their families, and their caregivers, and gain insight and support from their fellow staff members. A homeless man with head and neck cancer presents to the emergency room: a sad and familiar story. But this story is redeemed by his 35-year friendship with a priest, a man whose unconditional love and support became critical to the patient's care and treatment. The patient had lived for 30 years in homeless shelters, had problems with alcohol abuse, and was notoriously noncompliant with medical caregivers. He could not speak due to his disease, was illiterate with limited intellectual capacity, and had neither a job nor a family. Despite huge and apparently insurmountable problems for the patient, the oncology team was able to carve out a package of care, successfully communicate, and mobilize a support network to allow successful completion of chemoradiation therapy. The team developed a strong commitment to his care and an affectionate bond, which very positively affected all of those involved. We discuss issues of access to cancer care, and the special problems presented by homeless patients.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Addiction among cancer patients on strong analgesics is a rare but difficult management challenge. The case is presented of a 28-year-old woman with breast cancer and painful bone metastases, suffering with dysfunctional social chaos and addicted to Percocet (oxycodone and acetaminophen). Having broken the trust of her health care team, trust was rebuilt by incorporating the substance abuse clinic and enforcing a contractual agreement. With open and honest support, the team was able to both care for and empower the patient. Issues of trust, liability, opioid tolerance, and barriers to optimal analgesia for cancer pain are discussed.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to the caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers and gain insight and support from fellow staff members. We tell the story of one physician with incurable non-small cell lung cancer (NSCLC) who had an unexpectedly favorable response to an experimental treatment while receiving it as a part of his palliative care. His unique insight provides an opportunity to elucidate some of the issues that arise from living both as a patient-caregiver and as a cancer "surpriser." When caregivers face their own cancer, their reflections as patient-caregivers offer an internal perspective on the illness experience and help us as fellow caregivers to better understand and support all patients who face serious illnesses, both those who are colleagues and those who are not. Just like any patient with cancer, patient-caregivers experience the dramatic changes in health, daily life, and perspective that come with serious illness. Within the context of a life-threatening illness, caregiver-patients and their families search for new meaning as they face an uncertain future and address the issues of life and death. In addition to such processes, patient-caregivers with cancer also find that their own medical knowledge and their colleagues' reactions shape their experiences and to an extent separate them from those of other patients.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Clinicians in the field of oncology are unavoidably forced to break bad news. The Schwartz Center Rounds focuses on issues of communication between patients and their caregivers, one of the most difficult aspects of which is breaking bad news. The invited patient, a woman who had been living with a low-grade cancer for many years, spoke about her experiences both as a person living with cancer and as the daughter of a patient diagnosed with cancer. Her father's suicide, precipitated by being told his diagnosis, puts the horror of receiving bad news into stark relief. She provides a fascinating account of how she proactively adjusted to her diagnosis, and fought for optimal quality of life. This article discusses issues of support, abandonment, and how hope is conveyed, and reviews the literature that informs good clinical practice in breaking bad news.

Thalidomide was first introduced to the market in Germany under the brand name of Contergan in 1956, as a non-barbiturate hypnotic, advocated to ensure a good nights sleep and to prevent morning sickness in pregnancy. It was advertised for its prompt action, lack of hangover, and apparent safety. It has been banned from the market since 1963 after it caused the worldwide teratogenic disaster: babies exposed to thalidomide in utero during the first 34-50 days of pregnancy were born with severe life-threatening birth defects. Despite its unfortunate history, thalidomide has attracted scientific interest again because of its recently discovered action against inflammatory diseases and cancer. Its broad range of biological activities stems from its ability to moderate cytokine action in cancer and inflammatory diseases. Early studies examined its anxiolytic, mild hypnotic, antiemetic, and adjuvant analgesic properties. Subsequently, thalidomide was found to be highly effective in managing the cutaneous manifestations of leprosy, being superior to Aspirin in controlling leprosy-associated fever. Recent research has shown promising results with thalidomide in patients with myeloma, myelodysplastic syndrome, a variety of infectious diseases, autoimmune diseases, cancer, and progressive body weight loss related to advanced cancer and AIDS. Here we review the history of its development, pharmacokinetics, metabolism, biologic effects, and the results of clinical trials conducted thus far. Further research in this field should be directed towards better understanding of thalidomide metabolism, its mechanism of action, and the development of less toxic and more active analogs.

We hypothesized that incremental improvements in the cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) chemotherapy regimen through optimization of drug selection, schedule, and pharmacokinetics would improve outcome in patients with large B-cell lymphomas. A prospective multi-institutional study of administration of etoposide, vincristine, and doxorubicin for 96 hours with bolus doses of cyclophosphamide and oral prednisone (EPOCH therapy) was done in 50 patients with previously untreated large B-cell lymphomas. The doses of etoposide, doxorubicin, and cyclophosphamide were adjusted 20% each cycle to achieve a nadir absolute neutrophil count below 0.5 x 10(9)/L. The median age of the patients was 46 years (range, 20-88 years); 24% were older than 60 years; and 44% were at high-intermediate or high risk according to International Prognostic Index (IPI) criteria. There was a complete response in 92% of patients, and at the median follow-up time of 62 months, the progression-free survival (PFS) and overall survival (OS) rates were 70% and 73%, respectively. Neither IPI risk factors nor the index itself was associated with response, PFS, or OS. Doses were escalated in 58% of cycles, and toxicity levels were tolerable. Significant inverse correlations were observed between dose intensity and age for all adjusted agents, and drug clearance of doxorubicin and free etoposide was also inversely correlated with age (r = -0.54 and P(2) =.08 and r = -0.45 and P(2) =.034, respectively). Free-etoposide clearance increased significantly during successive cycles (P(2) =.015). Lymphomas with proliferation of at least 80% had somewhat lower progression and those expressing bcl-2 had significantly higher progression (P(2) =.04). Expression of bcl-2 may discriminate the recently described activated B-like from germinal-center B-like large-cell lymphomas and provide important pathobiologic and prognostic information. Dose-adjusted EPOCH may produce more cell kill than CHOP-based regimens. Dynamic dose adjustment may overcome inadequate drug concentrations, particularly in younger patients, and compensate for increased drug clearance over time.

Accumulating evidence suggests that the ability to activate apoptotic pathways may be an important determinant of chemotherapy sensitivity and presents a potentially important new therapeutic strategy. Monoclonal antibodies against the CD20 antigen directly induce apoptosis and may serve to modulate the threshold for chemotherapy-induced apoptosis. Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA), a monoclonal antibody against CD20, was combined with dose-adjusted EPOCH (infusional etoposide/vincristine/doxorubicin/bolus cyclophosphamide/prednisone) chemotherapy and tested in 38 untreated or relapsed poor-prognosis aggressive lymphomas. Twenty-three patients were untreated. Of these patients, all had large B-cell histologies, a median age of 52 years, Eastern Cooperative Oncology Group performance status > or = 2 in 30%, and high-intermediate or high International Prognostic Index scores in 61%. Fifteen patients had relapsed or refractory lymphomas. These patients had received a median of two (range, one to four) prior regimens, 67% had aggressive histologies, and 60% had high-intermediate or high International Prognostic Index scores. Complete remissions were achieved in 85% and 64% of untreated and previously treated patients, respectively; additionally 42% of patients with disease refractory before therapy achieved complete remission. At a median follow-up of 12 months, progression-free and overall survival in the previously untreated group was 85% and 79%, respectively, and no patient in complete remission has relapsed. These results suggest that rituximab may modulate the sensitivity of B-cell lymphomas to chemotherapy.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital, founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers and gain insight and support from fellow staff members. When a competent adult patient refuses lifesaving treatment for religious or personal reasons, caregivers have a legal obligation to respect this decision. A patient's refusal of treatment adds particular challenges to the delivery of compassionate care. The case of a 50-year-old Jehovah's Witness with acute myelocytic leukemia who declined blood product support is presented. Respecting her religious beliefs during chemotherapy required balancing risk and benefit, watching her suffer while unable to intervene with what the staff saw as simple treatment, and eventually undertaking a complicated grief process. Jehovah's Witness beliefs regarding blood products are reviewed. Caregiver roles and responsibilities are discussed in the context of psychosocial, legal, familial, and ethical issues.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital, founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Cancer in adolescents presents an extra dynamic of psychosocial complexity. The case of a 19-year-old woman with acute myelocytic leukemia is discussed. Her disease was refractory to allogeneic transplantation, and she died with severe graft-versus-host disease. Ms. P and her mother established very different relationships with the team which supported them through the transitions in her care, and Ms. P was able to die at home, with hospice care. The personal connection with the team enabled a degree of positive adjustment through the nightmare of loss. The epidemiology of cancer in adolescents and paradigms of care are reviewed. Psychosocial aspects of adolescence, opportunities for personal growth and support, and the challenge of end-of-life care are discussed.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital, founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Two vignettes are presented of a caregiver's response to the death of a patient, contrasting the extremes of involved compassion for the family and fractured relationships. Grief for loss is an inevitable part of life and a common part of cancer care. Support of the bereaved may be one of the hardest tasks for cancer care professionals, who are confronted with the limits of modern medicine. There is a responsibility to provide grieving families with support and care; care that goes beyond the death. A compassionate response helps both those who suffer and those who care. Complicated and uncomplicated bereavement, grief reactions, resources for bereavement counseling, and the role of condolence letters are reviewed.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. The 20th century success of the Internet is now translating into changes in 21st century medical practice. The changes brought about by the Internet have at once facilitated and complicated the practice of medicine. Physicians and patients are challenged to take advantage of the increased opportunities afforded by Internet access while being mindful of its drawbacks and the limitations to virtual communication. The case of Karen Parles, one of the authors, is presented. Karen developed locally advanced lung cancer and used the Internet to research her diagnosis. She found the information on lung cancer limited and confusing, and, in response, developed a website devoted to empowering lung cancer patients in their search for information and support (http://www.lungcanceronline.org). Here we discuss issues surrounding patients' use of the Internet for health information and communication with health care providers. The value of information-seeking as a coping mechanism is debated, and concerns are raised regarding confidentiality of electronic communications and the logistics of physicians adopting e-mail as a mechanism for communicating with patients.

Cancer treatment is evolving due to the development of molecularly targeted agents and the utilization of pharmacogenomics and pharmacogenetics to identify patients who are at an increased risk for toxicity or may be uniquely responsive to cytotoxic therapies. By identifying polymorphisms in the human genome that confer changes in the ability to metabolize or activate cancer agents, a more patient-specific treatment approach can be initiated. Molecularly targeted therapies such as PS-341, flavopiridol, Iressa, and anti-vascular endothelial growth factor antibodies may help to overcome resistance to cytotoxic therapies by lowering the apoptotic threshold and increasing cytotoxicity. Using molecularly targeted agents in combination with traditional cytotoxic agents may increase the percentage of patients who achieve disease stabilization and prolonged survival. With the development of genetic tools and genotyping of tumor and patient prior to initiating treatment, antitumor efficacy may be increased with a substantial reduction in toxicity.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Interest in complementary and alternative medicine (CAM) has grown exponentially in the past decade, fueled by Internet marketing, dissatisfaction with mainstream medicine, and a desire for patients to be actively involved in their health care. There is a large discordance between physician estimates and reported prevalence of CAM use. Many patients do not disclose their practices mainly because they believe CAM falls outside the rubric of conventional medicine or because physicians do not ask. Concern about drug interactions and adverse effects are compounded by a lack of Food and Drug Administration regulation. Physicians need to be informed about CAM and be attuned to the psychosocial needs of patients.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Caring for colleagues who develop cancer is a privilege woven with an extra dimension-caregiver-patient issues. As well as stretching the usual need for a supportive relationship, when one of the health care team develops cancer it particularly provokes concerns about our own mortality. The case is presented of a well-known physician who developed a second cancer and has been cared for at the MGH Cancer Center Staff discuss her care as it has been effected by her status as a colleague. They perceived unique barriers to optimal care such as assumptions about the patient's level of medical knowledge, and technical, informational, emotional, and hierarchical issues that may obstruct the development of a trusting relationship between caregivers and the physician/patient. Emotional stress may prevent the sharing of an accurate prognosis. In the case under consideration, the patient had a frank and open attitude to her cancer yet her caregivers were concerned about continual breeches of patient confidentiality. Despite the many potential problems inherent when the caregiver becomes the patient, this case discussion was a poignant reminder of the unique challenges of every experience with cancer and the weighty privilege of being involved with patient care.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Nebulous language, distrust, and dogma confound spiritual aspects of cancer care. However, existential well being is an important determinant of quality of life: finding meaning and purpose make suffering more tolerable. The case presented is of a patient who experienced "losing God" as a Hodgkin's disease survivor with metastatic prostate cancer and severe coronary artery disease. His caregivers were able to provide the sense of community in which he could re-establish his faith. Health care providers do not have to be religious in order to help patients to deal with a spiritual crisis. The clinical skills of compassion need to be deployed to diagnose and respond to spiritual suffering. Acknowledging and addressing anger or guilt, common sources of suffering, are essential to adjustment. Simply being there for the patient and being open to their hurt can help resolve their spiritual crisis, a responsibility that is shared by the whole health care team.