ONCOLOGY Vol 24 No 12

The review by Rampersaud and colleagues provides an excellent summary of the scientific rationale for using hyperthermia to treat cancer and of the current status of combinations of hyperthermia and chemotherapy or radiotherapy. In view of the demonstrated efficacy of the combination of intravescial hyperthermia and mitomycin C (MMC) therapy in preventing the progression and recurrence of non–muscle-invading bladder cancer (NMIBC) in several clinical trials, Rampersaud and colleagues advocate additional studies to further optimize the delivery of hyperthermia and to delineate its clinical utility in this disease.

Modern cancer care is characterized by a focus on organ-sparing multi-modal treatments. In the case of non–muscle-invasive bladder cancer this is particularly true; treatment is focused on reducing the frequency of low-risk recurrences and preventing high-risk progression. Deep regional hyperthermia is an oncologic therapeutic modality that can help achieve these two goals. The combination of hyperthermia with chemotherapy and radiotherapy has improved patient outcomes in several tumor types. In this review, we highlight the biology of therapeutic fever-range hyperthermia, discuss how hyperthermia is administered and dosed, demonstrate how heat can be added to other treatment regimens, and summarize the data supporting the role of hyperthermia in the management of bladder cancer.

Bladder cancer is the fourth most common cancer (excluding skin cancer) in the United States and ranks eighth as a cause of death from cancer among men; there will be an estimated 70,530 new cases and 14,680 cancer-related deaths in the United States in 2010.[1] Of new cases, 70% to 80% present with non–muscle-invasive bladder cancer (NMIBC). Despite endoscopic and intravesical treatments with curative intent, 50% to 70% of these cancers recur, usually within 5 years, and 10% to 30% progress to muscle-invasive disease, in the majority of cases as high-grade lesions.[2,3] Bladder cancer poses a significant economic burden due to the cost of the lifetime need for surveillance, the need to treat recurrent tumors, and the cost of complications associated with treatment. Medicare estimates have ranked bladder cancer treatment the seventh costliest among cancers, with a 5-year net cost of approximately one billion dollars.[4]

Influenza infection is a potential cause of additional morbidity and mortality in patients who are immunocompromised because of cancer or its treatment. Of particular note, influenza infection may delay or interrupt chemotherapy and necessitate hospitalization. Successful immunization depends on an intact immune system that can produce antibodies in response to antigen exposure. Patients with cancer often have a suppressed immune system, resulting from their disease and/or immunosuppressive therapies, and as a consequence they may have a suboptimal serologic response to influenza vaccination. Since vaccination is the only proven method for preventing influenza infection, the Advisory Committee on Immunization Practices recommends seasonal influenza vaccination for adults without contraindications who have disease- or medication-related immunosuppression. Patients with cancer should be given the trivalent inactivated vaccine. Preliminary data suggest that administering the vaccine between cycles of chemotherapy may yield the best results.

Influenza immunization can have four possible outcomes: (1) the vaccine is well tolerated and protects against subsequent infection; (2) the vaccine is not well tolerated-ie, it is associated with an excess risk of morbidity or mortality-but it protects against subsequent infection; (3) the vaccine is well tolerated but confers no protection; and (4) the vaccine is associated with morbidity and/or mortality and confers no protection. The CDC has evaluated the likelihood of each of these scenarios and recommends vaccination of cancer patients. Boehmer and colleagues have reviewed the efficacy data for influenza vaccination in cancer patients and have arrived at a more differentiated view.

Vitamin B12 is part of the vitamin B complex and is essential for maintaining nerve function, fatty acid metabolism, and DNA and amino acid synthesis. By lowering homocysteine levels, it may also protect against cardiovascular disease. Vitamin B12 can be obtained through diet (including eggs, dairy products, poultry, meat, and fortified cereals) and in supplement form. Deficiency of B12 can lead to a wide variety of hematologic, neurologic, and psychiatric disorders and may increase the risk of cardiovascular diseases. Clinical evidence to support the role of vitamin B12 in decreasing cancer risk is mixed. Further research is needed.

Despite the fact that elderly patients comprise over 50% of the non-small cell lung cancer (NSCLC) population, our knowledge regarding the efficacy and safety of chemotherapy in this group is suboptimal. The “elderly” (defined as individuals ≥70 years of age) experience physiologically normal aging of their bone marrow and kidneys, which inherently increases toxicity to therapy. Standard practice has often been to discourage the use of combination chemotherapy in these patients; however, general consensus guidelines emphasize that performance status should primarily guide the choice of treatment. Elderly patients with advanced NSCLC treated with platinum doublet therapy demonstrate similar efficacy (but increased toxicity) to their younger counterparts. Patients with metastatic disease in which a targeted and/or biological agent(s) was added to chemotherapy experienced benefits similar to those treated with standard platinum doublets, but with increased morbidity and mortality. In the future, effective testing of molecular targeted therapies will have to include elderly patients among research cohorts or risk excluding a large population of eligible patients. Overall, elderly patients with advanced NSCLC, while experiencing greater toxicity, demonstrate the same response rates and survival benefits as their younger peers.

Calendar age and biological age do not always correspond. Pablo Picasso, source of the quote that begins the title of this commentary, lived a notoriously robust and active life through his later decades, dying in his nineties in the midst of a dinner party. In the oncology community, with the advent of targeted therapeutics and better supportive care, the disparity between the two is likely to be increasingly relevant to both research and practice. In this issue of ONCOLOGY, Chiappori et al review data supporting the idea that even in the context of standard cytotoxic chemotherapy, elderly patients with advanced NSCLC experience similar response rates and similar survival benefits to those seen in younger patients. They note that biases excluding elderly patients from clinical trials result in gaps in our knowledge of how to best treat older patients.

The review by Dr. Chiappori and colleagues in this issue of ONCOLOGY addresses an important challenge relating to the optimal management of elderly patients with lung cancer. The authors provide an excellent overview of the data in patients with various stages of non-small cell lung cancer (NSCLC). They also highlight the limitations of the existing data in the management of elderly NSCLC patients.

Recent developments in the epidemiology, staging, and treatment of esophageal and gastroesophageal junction cancers have led to significant changes in the way these malignancies are managed. Although a relationship between gastroesophageal reflux disease and esophageal cancer has been demonstrated, antireflux surgery has been shown to have no preventive effect with regard to the development of esophageal adenocarcinoma. The newly modified staging system of the World Esophageal Cancer Consortium has helped define the optimal number of lymph nodes to dissect during an esophagectomy. Incorporating modern techniques, such as esophageal ultrasound, fine needle aspiration, and positron emission tomography, can improve the prognostic value of staging. Use of higher-volume centers and higher-volume surgeons for the performance of procedures in upper gastrointestinal cancers is associated with better outcomes. Neoadjuvant chemoradiation using a wide variety of chemotherapy regimens appears to have become the new standard of care for stage II and III esophageal cancer.

Nothing gets biopharma policy watchers more worked up than the possibility that the Centers for Medicare & Medicaid Services (CMS) will second-guess FDA approval decisions. In reality, though, CMS often has no choice but to apply its own interpretation to issues that also fall under the FDA’s jurisdiction-and implementation of the health care reform is bringing more of those cases to the fore.

FROM THE SOON-TO-BE RELEASED 13TH EDITION OF THE CANCER MANAGEMENT HANDBOOK

Esophageal adenocarcinoma (EAC) affects approximately 11,000 persons per year in the United States, is increasing in incidence, and is associated with an exceptionally high mortality rate.[1-4] In this issue of ONCOLOGY, Krasna reviews the role of multimodality therapy in the treatment of EAC. Poor outcome in patients with EAC is reflective of both deficiencies in early detection and the inadequacy of available therapies across stages.

Dr. Krasna has written an overview of multimodality therapy in esophageal cancer, with a particular focus on aspects related to staging and surgical care. The optimal management of locally advanced esophageal cancer remains a subject of controversy and active debate. However, there is now a clear consensus that surgery alone is inadequate therapy for patients with T3 or node-positive disease.