Daniel Shasha

Cancer-Related Anemia: Pathogenesis, Prevalence and Treatment

Cancer-related anemia is a cytokine-mediated disorder resulting from complex interactions between tumor cells and the immune system. Overexpression of certain inflammatory cytokines results in shortened survival of red blood cells, suppression of erythroid progenitor cells, impaired iron utilization, and inadequate erythropoietin production. Numerous other factors may also contribute to the development of anemia in cancer patients. The European Cancer Anaemia Survey (ECAS) has provided the most current, comprehensive, prospectively collected data on the incidence and prevalence of anemia among cancer patients, as well as important perspectives on anemia treatment and relationship of hemoglobin and performance status. ECAS enrolled over 15,000 treated and untreated patients with various malignancies from cancer centers in 24 European countries and followed them for up to 6 months. The initial analysis of the ECAS data revealed that 39% of the total cancer patient population was anemic (hemoglobin <12.0 g/dl) at enrollment, although the rate varied according to tumor type, disease status, and cancer treatment status. Of the patients who were not anemic at enrollment and started cancer treatment during the survey, those undergoing chemotherapy – either alone or in combination with radiotherapy – had the highest incidence of anemia (63 and 42%, respectively). Low hemoglobin levels correlated with poor performance status and only 40% of patients who were anemic at some time during the survey received treatment for their anemia. These findings are noteworthy, since a growing body of clinical evidence indicates that the treatment of anemia can significantly improve patients’ quality of life and may also improve the clinical outcome.

The American Brachytherapy Society recommendations for brachytherapy of soft tissue sarcomas

PURPOSE This report presents the American Brachytherapy Society (ABS) guidelines for the use of brachytherapy for patients with soft tissue sarcoma. METHODS AND MATERIALS Members of the ABS with expertise in soft tissue sarcoma formulated brachytherapy guidelines based upon their clinical experience and a review of the literature. The Board of Directors of the ABS approved the final report. RESULTS Brachytherapy used alone or in combination with external beam irradiation is an established means of safely providing adjuvant local treatment after resection for soft tissue sarcomas in adults and in children. Brachytherapy options include low dose rate techniques with iridium 192 or iodine 125, fractionated high dose rate brachytherapy, or intraoperative high dose rate therapy. Recommendations are made for patient selection, techniques, dose rates, and dosages. Complications and possible interventions to minimize their occurrence and severity are reviewed. CONCLUSION Brachytherapy represents an effective means of enhancing the therapeutic ratio, offering both biologic and dosimetric advantage in the treatment of patients with soft tissue sarcoma. The treatment approach used depends upon the institution, physician expertise, and the clinical situation. Guidelines are established for the use of brachytherapy in the treatment of soft tissue sarcomas in adults and in children. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose-reporting policies. These guidelines will be modified, as further clinical results become available.

Prevalence of anemia in cancer patients undergoing radiation therapy

Anemia is associated with reduced local tumor control and impaired quality of life in patients with several types of solid tumors. The prevalence of anemia in patients who present at radiation oncology departments has not been well documented, and the impact of anemia on the outcome of radiation therapy is not widely appreciated in the radiation oncology setting. In an ongoing study, we are retrospectively reviewing the medical charts of patients before and after radiation therapy at our institutions to determine the magnitude of the anemia problem in this population. Preliminary data are available for 574 randomly selected patients (52% female) seen between December 1996 and June 1999. At presentation, 41% of all patients were anemic (hemoglobin < 12 g/dL); by the end of radiation therapy, this percentage increased to 54%. The most common tumor types were prostate (16%), breast (14%), head and neck (12%), colorectal (11%), lung/bronchus (11%), and uterine-cervix (9%). Anemia was most prevalent in patients with uterine-cervical tumors (75%), increasing to 79% by the end of radiation therapy. The prevalence of lung/bronchus and colorectal cancer was 55% and 44%, respectively, at baseline and increased to 77% and 63%, respectively, after radiation therapy. For nearly all tumor types, the majority of patients had or developed mild to moderate anemia (hemoglobin 10.0 to 11.9 g/dL). These data show that anemia is widespread among patients seen in radiation oncology practices. However, the anemia is usually mild and readily correctable. Because anemia and hypoxia possibly associated with anemia are obstacles to local tumor control and maintenance of quality of life, strategies to reverse anemia should receive greater attention.

ELECTIVE IRRADIATION OF THE N0 NECK IN SQUAMOUS CELL CARCINOMA OF THE UPPER AERODIGESTIVE TRACT

The decision of how to optimally manage the clinically negative neck is based on the likelihood of clinically inapparent disease and the efficacy of salvage therapy. The criteria of decision for elective management of the neck takes into account the site, size, depth of infiltration, grading of the primary lesion, clinical and radiologic evaluation, and patient wishes. Diagnostic procedures currently used in evaluating head and neck cancer patients with nodal disease are reviewed. Elective irradiation of the N0 neck in patients with squamous cell carcinoma of the head and neck is an effective means of maintaining locoregional control. The impact of elective nodal treatment on disease free survival and overall survival is discussed.

Standard of Care for Cancer-Related Anemia: Improving Hemoglobin Levels and Quality of Life

The introduction of recombinant human erythropoietin (rHuEPO) has proven to be a major advance in the therapeutic options available for managing anemia in cancer patients. The results of placebo-controlled clinical trials and large, community-based, open-label studies have confirmed that epoetin alfa, a recombinant human erythropoietin, significantly reduces transfusion requirements, and reliably increases hemoglobin (Hb) levels in anemic (Hb level <12 g/dl) cancer patients undergoing chemotherapy. Increased Hb improves patients’ energy level and their ability to perform the activities of daily living, as well as their overall quality of life (QOL). These findings are independent of tumor type and disease status and are comparable in patients receiving nonplatinum- and platinum-based chemotherapeutic regimens. Furthermore, more than a decade of use in clinical trials and by physicians in routine clinical practice has demonstrated that epoetin alfa is safe and well tolerated when used to treat cancer patients with anemia. The availability of epoetin alfa as an alternative to transfusion has changed practices in anemia management; physicians can now treat anemia with the goal of achieving adequate Hb levels to relieve anemia-related fatigue, a major symptom contributing to decreased QOL in cancer patients. Incremental benefit analysis has shown that increasing Hb level from 11 g/dl to 12 g/dl yields the greatest improvement in QOL per 1 g/dl increase in Hb. The demonstrated efficacy of epoetin alfa for increasing Hb levels and improving patient QOL have made this agent a rationale choice for management of cancer-related anemia. Ongoing research will continue to provide new insights into best management of anemia with epoetin alfa in cancer patients.

Contemporary management of localized penile cancer

This article reviews the etiology, clinical presentation and diagnosis of localized penile cancer. We summarize the current literature concerning recent trends and advances in the treatment of localized penile cancer (<T2, node negative [N0]) through the use of a systematic review and meta-analysis. We discuss a generalized overview of the current treatment options. A total of 54 review articles, retrospective studies and case reports on conservative penile treatments were reviewed and screened for data on the efficacy of numerous therapies in carcinoma in situ, T1N0 and T2N0 patients. These data were analyzed, tabulated and discussed. Even though recurrence rates are higher in patients receiving penile-sparing options (compared with patients receiving radical penectomy), the locally recurrent cancers are highly treatable and these patients experience a higher quality of life.

Exploration of the Role of Radiotherapy in the Management of Early Glottic Cancer with Complete Carotid Artery Occlusion

Background: The aim of this study was to compare intensity-modulated radiation therapy (IMRT) vs. 2D and 3D radiotherapy (RT) in the treatment of T1 glottic squamous cell carcinoma in an effort to highlight the advantages of IMRT in this particular clinical situation. Case Report: We present the case of an 82-year-old female patient with T1 left true vocal cord squamous cell carcinoma and complete occlusion of the left carotid artery resulting in multiple strokes. The patient underwent definitive RT with 63 Gy (28 × 2.25 Gy). 3 plans were generated: 2D RT, 3D RT, and IMRT. The right carotid artery (Rt.CA) mean dose was 865, 2,065, and 4,268 cGy for IMRT, 3D RT, and 2D RT, respectively. The inferior pharyngeal constrictor (IPC) mean dose was 5,341, 6,456, and 6,451 cGy for IMRT, 3D RT, and 2D RT, respectively. IMRT provided the best homogeneity but at a higher cost and with prolonged treatment time. Conclusion: IMRT provided the finest planning target volume coverage with minimal Rt.CA and IPC doses. IMRT is recommended in certain clinical scenarios which are not manageable with other techniques.

Clinical validation and applications for CT-based atlas for contouring the lower cranial nerves for head and neck cancer radiation therapy

OBJECTIVES Radiation induced cranial nerve palsy (RICNP) involving the lower cranial nerves (CNs) is a serious complication of head and neck radiotherapy (RT). Recommendations for delineating the lower CNs on RT planning studies do not exist. The aim of the current study is to develop a standardized methodology for contouring CNs IX-XII, which would help in establishing RT limiting doses for organs at risk (OAR). METHODS Using anatomic texts, radiologic data, and guidance from experts in head and neck anatomy, we developed step-by-step instructions for delineating CNs IX-XII on computed tomography (CT) imaging. These structures were then contoured on five consecutive patients who underwent definitive RT for locally-advanced head and neck cancer (LAHNC). RT doses delivered to the lower CNs were calculated. RESULTS We successfully developed a contouring atlas for CNs IX-XII. The median total dose to the planning target volume (PTV) was 70Gy (range: 66-70Gy). The median CN (IX-XI) and (XII) volumes were 10c.c (range: 8-12c.c) and 8c.c (range: 7-10c.c), respectively. The median V50, V60, V66, and V70 of the CN (IX-XI) and (XII) volumes were (85, 77, 71, 65) and (88, 80, 74, 64) respectively. The median maximal dose to the CN (IX-XI) and (XII) were 72Gy (range: 66-77) and 71Gy (range: 64-78), respectively. CONCLUSIONS We have generated simple instructions for delineating the lower CNs on RT planning imaging. Further analyses to explore the relationship between lower CN dosing and the risk of RICNP are recommended in order to establish limiting doses for these OARs.

AN INTERNET-READY DATABASE FOR PROSPECTIVE RANDOMIZED CLINICAL TRIALS OF HIGH-DOSE-RATE BRACHYTHERAPY FOR ADENOCARCINOMA OF THE PROSTATE

PURPOSE To demonstrate a new interactive Internet-ready database for prospective clinical trials in high-dose-rate (HDR) brachytherapy for prostate cancer. METHODS AND MATERIALS An Internet-ready database was created that allows common data acquisition and statistical analysis. Patient anonymity and confidentiality are preserved. These data forms include all common elements found from a survey of the databases. The forms allow the user to view patient data in a view-only or edit mode. Eight linked forms document patient data before and after receiving HDR therapy. The pretreatment forms are divided into four categories: staging, comorbid diseases, external beam radiotherapy data, and signs and symptoms. The posttreatment forms separate data by HDR implant information, HDR medications, posttreatment signs and symptoms, and follow-up data. The forms were tested for clinical usefulness. CONCLUSION This Internet-based database enables the user to record and later analyze all relevant medical data and may become a reliable instrument for the follow-up of patients and evaluation of treatment results.

PSA outcomes in patients with adenocarcinoma of the prostate with presenting PSA > 20 ng/ml.

241 Background: Optimal treatment of prostate cancer with presenting PSA >20 ng/mL is debated within and between specialties, as reflected by variable PSA outcomes reported. We present our clinical outcomes in irradiated patients for this population. METHODS With IRB approval, we analyzed patient, disease, treatment, and PSA data of 149 patients with presenting PSA > 20 ng/mL radiated with curative intent 1997-2012 by a single physician (DS) at Beth Israel Medical Center (New York City). External beam radiation therapy (EBRT) was delivered first to prostate, seminal vesicles (SV) and draining pelvic lymph nodes to 45 Gy, then 5.4 Gy cone down, then a boost with either brachytherapy (BT) or 30.6 Gy conformal EBRT. BT was withheld in large volume of SV invasion by either DRE or by MRI. Hormonal therapy (HT) consisted of LHRH agonist +/- antiandrogen therapy. PSA was checked every 6 mos. Biochemical Failure (BF) was defined as post-treatment PSA nadir + 2 ng/mL. RESULTS 41% of patients were African American, 27% Hispanic, 21% Caucasian, and 6% Asian. The median patient age, Gleason score (GS), PSA, and T stage were 68 yrs (range 42-87), 30 ng/mL (range 20-280), 7 (range 5-10) and stage II (8% Tx, 29% T1, 32% T2, 22% T3a/b, 8% T3c). Combined EBRT and BT (CMT) were used in 70% (N=104); EBRT alone in 28% (N=42); BT alone in 2% (N=3). HT was given to 87% (N=129), (median duration 25 mos). Of CMT patients, 77% (N=81) had I-125 permanent seed implant, 22% (N=23) had Pd-103 implant, and 1% (N=1) had HDR temporary Ir-192 implant. With a minimum follow-up (FU) 2 years and median FU 4.9 years (range 2.0-14.1), overall BF was 18% (N=27), and median time to failure was 4 yrs (range 0.4-9.3). Of failures, median age was 64 (range 48-83), and 40% were African American; median pre-treatment PSA was 40 ng/mL (range 20-238), median stage was 3. BF occurred in 17/104 (16.3%) CMT patients (13/17 I-125 and 3/17 Pd-103), 9/42 (21.4%) EBRT patients, and 1/3 (33%) BT alone patients (1/1 I-125). All patients who failed received HT. CONCLUSIONS Excellent overall biochemical outcomes in patients with presenting PSA > 20 ng/ml are reported, with only approximately 18% experiencing BF at a median FU of 4.9 years. Of all treatments analyzed, CMT yielded superior biochemical control.