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Joel E Tepper

Publications and source records attributed to Joel E Tepper.

At least 19 recordsLinked to original sources
PubMed2006

Complications associated with neoadjuvant radiotherapy in the multidisciplinary treatment of retroperitoneal sarcomas.

INTRODUCTION: Retroperitoneal sarcomas (RPS) remain a therapeutic challenge due to high local recurrence rates. Preoperative RT offers theoretical advantages in the multidisciplinary care of RPS. The purpose of our study was to evaluate our experience using preoperative radiotherapy (PRT) in the treatment of RPS. METHODS: This is a single-institution review of patients with RPS treated with PRT from 1994 until 2004. Three radiation oncologists and four surgical oncologists were involved. Medical records, tumor registries, and death records were reviewed. RESULTS: Fourteen patients were included; nine were treated for primary presentation and five for recurrent disease. Histologic grade was grade I (n = 3), grade II (n = 3), and grade III (n = 8). Five patients received additional IORT. Radiotherapy complications were generally mild, including nausea (n = 3), diarrhea (n = 1), dehydration (n = 1), anemia (n = 1), and skin changes (n = 1); one required early cessation due to nausea. Thirteen patients had gross negative margins; while 7/13 had negative microscopic margins. Operative complications included anastomotic bleeding (n = 1), fluid collections (n = 2), ileus (n = 3), ascites (n = 2), temporary leg weakness (n = 1), and uncomplicated wound infections (n = 2). In patients with R0 or R1 resections, one and two year local control rates were 64 and 50%. Overall survival for all patients was 90% at 1 year and 74% at 2 years with median survival of 21 months. CONCLUSION: PRT and IORT can be administered effectively in carefully selected patients with resectable RPS. Larger multi-center studies are needed to delineate the role of PRT and IORT to improve local recurrence and survival rates in the treatment of RPS.

Aged↗
PubMed2006

Cancer and leukemia group B gastrointestinal cancer committee.

The Cancer and Leukemia Group B Gastrointestinal Cancer Committee was organized in the late 1970s under the leadership of Michael Perry and Philip Schein and began full-scale operations in the mid-1980s. Today, it is a multidisciplinary team of surgeons, radiation and medical oncologists, statisticians, quality-of-life experts, pharmacogeneticists, basic scientists, and community oncologists who design studies that are conducted across the United States. The Committee has done trials in patients with esophageal, gastric, pancreatic, colon, rectal, and anal cancers. New initiatives are under way in hepatocellular cancer, cholangiocarcinoma, and neuroendocrine tumors originating in the gastrointestinal tract. The Committee has increasingly concentrated on translational studies using tumor blocks, germ-line DNA, and plasma to evaluate biological correlates of tumor response and clinical outcomes. A broad program of pharmacogenomics has been incorporated for virtually all studies, including trials that prospectively use polymorphisms in drug-metabolizing genes to assign treatments. Future efforts aim to evolve new standards of care, evaluate new therapies, and answer relevant biological questions in gastrointestinal cancer.

Antineoplastic Agents↗
PubMed2006

Phase I/II study of preoperative oxaliplatin, fluorouracil, and external-beam radiation therapy in patients with locally advanced rectal cancer: Cancer and Leukemia Group B 89901.

PURPOSE: The addition of oxaliplatin to fluorouracil in patients with advanced colorectal cancer improves survival. This phase I/II study evaluated the addition of weekly oxaliplatin to preoperative continuous infusion fluorouracil (FU) and external-beam radiation therapy (RT) in patients with locally advanced rectal adenocarcinoma. PATIENTS AND METHODS: Patients with clinical T3/T4 rectal adenocarcinoma and no evidence of metastases were treated with weekly oxaliplatin, continuous infusion FU 200 mg/m2 intravenously, and RT. A total of 6 weekly doses of oxaliplatin were planned. RT dose was 1.8 Gy/fraction to a total dose of 50.4 Gy. In the phase I portion, oxaliplatin was escalated from 30 to 60 mg/m2. RESULTS: Forty-four patients were entered onto the study, 18 on the phase I portion and 26 on the phase II portion. The maximum-tolerated dose (MTD) for oxaliplatin was determined to be 60 mg/m2. At the MTD, 12 patients experienced grade 3 or 4 diarrhea, two patients experienced grade 3 neutropenia, and one patient experienced grade 3 thrombocytopenia. Fifty-six percent of patients entered at the MTD completed all 6 weeks of oxaliplatin. Eight (25%) of 32 patients enrolled at the phase II dose experienced a pathologic complete response. CONCLUSION: In this multicenter study, the addition of oxaliplatin to intravenous continuous infusion FU and RT for patients with locally advanced rectal cancer was associated with a high pathologic complete response rate but more toxicity than when FU is used alone. A regimen of weekly oxaliplatin, continuous infusion FU, and radiation therapy is now being evaluated by the National Surgical Adjuvant Breast and Bowel Project.

Adenocarcinoma↗
PubMed2005

Risk of pelvic fractures in older women following pelvic irradiation.

CONTEXT: Pelvic fractures, including hip fractures, are a major source of morbidity and mortality in older women. Although therapeutic pelvic irradiation could increase the risk of such fractures, this effect has not been studied. OBJECTIVE: To determine if women who undergo pelvic irradiation for pelvic malignancies (anal, cervical, or rectal cancers) have a higher rate of pelvic fracture than women with pelvic malignancies who do not undergo irradiation. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked to Medicare claims data. A total of 6428 women aged 65 years and older diagnosed with pelvic malignancies from 1986 through 1999 were included. We compared results for women who did (n = 2855) vs did not (n = 3573) undergo radiation therapy. To assess the influence of selection bias, we also evaluated the effect of irradiation on osteoporotic fractures in nonirradiated sites (arm and spine). MAIN OUTCOME MEASURE: We evaluated the effect of irradiation on the incidence of pelvic fractures over time, and adjusted for potential confounders using a proportional hazards model. RESULTS: Women who underwent radiation therapy were more likely to have a pelvic fracture than women who did not undergo radiation therapy (cumulative 5-year fracture rate, 14.0% vs 7.5% in women with anal cancer, 8.2% vs 5.9% in women with cervical cancer, and 11.2% vs 8.7% in women with rectal cancer); the difference was statistically significant and most fractures (90%) were hip fractures. We controlled for potential confounders including age, race, cancer stage, and geographic location. The impact of irradiation varied by cancer site: treatment for anal cancer was associated with a higher risk of pelvic fractures (hazard ratio, 3.16; 95% confidence interval, 1.48-6.73); than for cervical cancer (hazard ratio, 1.66; 95% confidence interval, 1.06-2.59); or rectal cancer (hazard ratio, 1.65; 95% confidence interval, 1.33-2.05). No statistically significant difference was found in the rate of arm or spine fractures between the irradiated and nonirradiated groups (hazard ratio, 1.15; 95% confidence interval, 0.89-1.48). CONCLUSIONS: Pelvic irradiation substantially increases the risk of pelvic fractures in older women. Given the high baseline risk of pelvic fracture, this finding is of particular concern.

Aged↗
PubMed2005

Evidence-based review of three-dimensional conformal radiotherapy for localized prostate cancer: an ASTRO outcomes initiative.

PURPOSE: To perform a systematic review of the evidence to determine the efficacy and effectiveness of three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer; provide a clear presentation of the key clinical outcome questions related to the use of 3D-CRT in the treatment of localized prostate cancer that may be answered by a formal literature review; and provide concise information on whether 3D-CRT improves the clinical outcomes in the treatment of localized prostate cancer compared with conventional RT. METHODS AND MATERIALS: We performed a systematic review of the literature through a structured process developed by the American Society for Therapeutic Radiology and Oncology's Outcomes Committee that involved the creation of a multidisciplinary task force, development of clinical outcome questions, a formal literature review and data abstraction, data review, and outside peer review. RESULTS: Seven key clinical questions were identified. The results and task force conclusions of the literature review for each question are reported. CONCLUSION: The technological goals of reducing morbidity with 3D-CRT have been achieved. Randomized trials and follow-up of completed trials remain necessary to address these clinical outcomes specifically with regard to patient subsets and the use of hormonal therapy.

Disease-Free Survival↗
PubMed2005

Impact of preoperative radiation for rectal cancer on subsequent lymph node evaluation: a population-based analysis.

PURPOSE: To determine the impact of preoperative radiotherapy (RT) on the accuracy of lymph node staging (LNS). Preoperative RT is a well-established component of rectal cancer treatment but its impact on LNS is unknown. METHODS AND MATERIALS: The Surveillance, Epidemiology and End Results (SEER) registry, representing 14% of the U.S. population, was used to assess the impact of preoperative RT on LNS. Our study population consisted of adults with rectal cancer between 1998 and 2000 who underwent radical resection. RESULTS: In our 3-year study period, 5647 patients met the selection criteria and 1034 (19.5%) underwent preoperative RT. The preoperative RT group was younger (average age, 61 years) than those who did not undergo preoperative RT (average age, 69 years) and more likely to be male (22% of men vs. 16% of women). On average, fewer nodes were examined in patients who underwent preoperative RT (7 nodes) vs. those who did not (10 nodes); this difference was statistically significant, controlling for potential confounders (p < or = 0.0001). In 16% of the preoperative RT patients (vs. 7.5% without), no nodes were identified (p < or = 0.0001). If one used a minimum of 12 nodes as the standard, only 20% of patients who underwent preoperative RT underwent adequate LNS. CONCLUSION: Lymph node staging in patients who undergo preoperative RT must be interpreted with caution. Studies are needed to evaluate the clinical relevance of node number and pathologic staging after preoperative RT for rectal cancer.

Aged↗
PubMed2005

Increased risk of rectal cancer after prostate radiation: a population-based study.

BACKGROUND & AIMS: Radiation therapy for prostate cancer has been associated with an increased rate of pelvic malignancies, particularly bladder cancer. The association between radiation therapy and colorectal cancer has not been established. METHODS: We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) registry data from 1973 through 1994. We focused on men with prostate cancer, but with no previous history of colorectal cancer, treated with either surgery or radiation who survived at least 5 years. We evaluated the effect of radiation on development of cancer for 3 sites: definitely irradiated sites (rectum), potentially irradiated sites (rectosigmoid, sigmoid, and cecum), and nonirradiated sites (the rest of the colon). Using a proportional hazards model, we evaluated the effect of radiation on development of colorectal cancer over time. RESULTS: A total of 30,552 men received radiation, and 55,263 underwent surgery only. Colorectal cancers developed in 1437 patients: 267 in irradiated sites, 686 in potentially irradiated sites, and 484 in nonirradiated sites. Radiation was independently associated with development of cancer over time in irradiated sites but not in the remainder of the colon. The adjusted hazards ratio for development of rectal cancer was 1.7 for the radiation group, compared with the surgery-only group (95% CI: 1.4-2.2). CONCLUSIONS: We noted a significant increase in development of rectal cancer after radiation for prostate cancer. Radiation had no effect on development of cancer in the remainder of the colon, indicating that the effect is specific to directly irradiated tissue.

Aged↗
PubMed2005

Staging of colorectal cancer: past, present, and future.

Since the inception of staging for colorectal cancer (CRC), anatomic extent of disease has provided a solid foundation for predicting prognosis and guiding treatment in patients with CRC. However, the rapid advances in biologic and genetic technology have provided many new possibilities for enhancing the predictive power of the staging system. In this article, we will briefly discuss the history of CRC staging, identify the current parameters for American Joint Committee on Cancer staging including recent changes, and offer guidelines for future staging modifications. Although anatomic parameters have served us well for many years, their continued use as sole contributors to CRC staging is questionable. Staging in the future is likely to be a complicated combination of anatomic and biologic markers used together in mathematic modeling to group patients into prognostic risk groups, which can be used to guide tailored therapy.

Colorectal Neoplasms↗
PubMed2004

Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: a pooled analysis.

PURPOSE: To determine survival and relapse rates by T and N stage and treatment method in five randomized phase III North American rectal adjuvant studies. PATIENTS AND METHODS: Data were pooled from 3,791 eligible patients enrolled onto North Central Cancer Treatment Group (NCCTG) 79-47-51, NCCTG 86-47-51, US Gastrointestinal Intergroup 0114, National Surgical Adjuvant Breast and Bowel Project (NSABP) R01, and NSABP R02. Surgery alone (S) was the treatment arm in 179 patients. The remaining patients received adjuvant treatment as follows: irradiation (RT) alone (n = 281), RT + fluorouracil (FU) +/- semustine bolus chemotherapy (CT; n = 779), RT + protracted venous infusion CT (n = 325), RT + FU +/- leucovorin or levamisole bolus CT (n = 1,695), or CT alone (n = 532). Five-year follow-up was available in 94% of surviving patients, and 8-year follow-up, in 62%. RESULTS: Overall (OS) and disease-free survival were dependent on TN stage, NT stage, and treatment method. Even among N2 patients, T substage influenced 5-year OS (T1-2, 67%; T3, 44%; T4, 37%; P <.001). Three risk groups of patients were defined: (1) intermediate (T1-2/N1, T3/N0), (2) moderately high (T1-2/N2, T3/N1, T4/N0), and (3) high (T3/N2, T4/N1, T4/N2). For intermediate-risk patients, those receiving S plus CT had 5-year OS rates of 85% (T1-2/N1) and 84% (T3/N0), which was similar to results with S plus RT plus CT (T1-2/N1, 78% to 83%; T3/N0, 74% to 80%). For moderately high-risk lesions, 5-year OS ranged from 43% to 70% with S plus CT, and 44% to 80% with S plus RT plus CT. For high-risk lesions, 5-year OS ranged from 25% to 45% with S plus CT, and 29% to 57% with S plus RT plus CT. CONCLUSION: Different treatment strategies may be indicated for intermediate-risk versus moderately high- or high-risk patients based on differential survival rates and rates of relapse. Use of trimodality treatment for all patients with intermediate-risk lesions may be excessive, since S plus CT resulted in 5-year OS of approximately 85%; however, 5-year disease-free survival rates with S plus CT were 78% (T1-2/N1) and 69%(T3/N0), indicating room for improvement.

Adult↗
PubMed2004

Impact of body mass index on outcomes and treatment-related toxicity in patients with stage II and III rectal cancer: findings from Intergroup Trial 0114.

PURPOSE: To study the relationship between body mass index (BMI) and rates of sphincter-preserving operations, overall survival, cancer recurrence, and treatment-related toxicities in patients with rectal cancer. PATIENTS AND METHODS: We evaluated a nested cohort of 1,688 patients with stage II and III rectal cancer participating in a randomized trial of postoperative fluorouracil-based chemotherapy and radiation therapy. RESULTS: Obese patients were more likely to undergo an abdominoperineal resection (APR) than normal-weight patients (odds ratio, 1.77; 95% CI, 1.27 to 2.46). When analyzed by sex, increasing adiposity in men was a strong predictor of having an APR (P <.0001). Obese men with rectal cancer were also more likely than normal-weight men to have a local recurrence (hazard ratio [HR], 1.61; 95% CI, 1.00 to 2.59). In contrast, obesity was not predictive of cancer recurrence in women, nor was BMI predictive of overall mortality in either men or women. Underweight patients had an increased risk of death (HR, 1.43; 95% CI, 1.08 to 1.89) compared with normal-weight patients but no increase in cancer recurrences. Among all study participants, obese patients had a significantly lower rate of grade 3 to 4 leukopenia, neutropenia, and stomatitis and a lower rate of any grade 3 or worse toxicity when compared with normal-weight individuals. CONCLUSION: Increasing BMI in male patients with rectal cancer is associated with a decreased likelihood of sphincter preservation and a higher chance of local recurrence. For both men and women, overweight and obese patients experience less toxicity associated with adjuvant chemoradiotherapy, suggesting that actual body weight dosing of fluorouracil for obese patients is justified.

Antineoplastic Agents↗
PubMed2004

Impact of hospital procedure volume on surgical operation and long-term outcomes in high-risk curatively resected rectal cancer: findings from the Intergroup 0114 Study.

PURPOSE: Prior studies have demonstrated superior outcomes after a curative surgical resection of rectal cancer at hospitals where the volume of such surgeries is high. However, because these studies often lack detailed information on tumor and treatment characteristics as well as cancer recurrence, the true nature of this relation remains uncertain. PATIENTS AND METHODS: We studied a nested cohort of 1,330 patients with stage II and stage III rectal cancer participating in a multicenter, adjuvant chemoradiotherapy trial. We analyzed differences in rates of sphincter-preserving operations, overall survival, and cancer recurrence by hospital surgical volume. RESULTS: We observed a significant difference in the rates of abdominoperineal resections across tertiles of hospital procedure volume (46.3% for patients resected at low-volume, 41.3% at medium-volume, and 31.8% at high-volume hospitals; P <.0001), even after adjustment for tumor distance from the anal verge. However, this higher rate of sphincter-sparing operations at high-volume centers was not accompanied by any increase in recurrence rates. Hospital surgical volume did not predict overall, disease-free, recurrence-free, or local recurrence-free survival. However, among patients who did not complete the planned adjuvant chemoradiotherapy (270 patients), those who underwent surgery at low-volume hospitals had a significant increase in cancer recurrence (adjusted hazard ratio, 1.94; 95% CI, 1.01 to 3.72; P =.04 for the trend) and a nonsignificant trend toward increased overall mortality (P =.08) and local recurrence (P =.10). In contrast, no significant volume-outcome relation was noted among patients who did complete postoperative therapy. CONCLUSION: Using prospectively recorded data, we found that hospital surgical volume had no significant effect on rectal cancer recurrence or survival when patients completed standard adjuvant therapy. Sphincter-preserving surgery was more commonly performed at high-volume centers.

Adult↗
PubMed2003

Cancer and leukemia group B (CALGB) 89805: phase II chemoradiation trial using gemcitabine in patients with locoregional adenocarcinoma of the pancreas.

PURPOSE: Determine the safety and efficacy of twice weekly gemcitabine and concurrent radiation to the upper abdomen followed by weekly gemcitabine in patients with surgically staged, locally advanced pancreatic cancer. METHODS: Patients with surgically staged, locally advanced, nonmetastatic adenocarcinoma of the pancreas were treated with intravenous gemcitabine administered twice weekly (40 mg/m2/d) for 5 wk concurrent with upper abdominal radiation (50.4 Gy in 180 cGy daily fractions over 5.5 wk). At the completion of the chemoradiation, patients without disease progression were given gemcitabine (1000 mg/m2) weekly for five cycles. Each cycle consisted of 3 wk of treatment followed by 1 wk without treatment. Disease progression and response were assessed at 6- to 8-wk intervals. RESULTS: From February through December 1999, 43 patients were entered into this phase II trial, 39 of whom were evaluable for treatment response. The median age was 59 yr (range: 39-84 yr); there were 18 males (47%) in the study. Grade III and IV hematologic toxicity occurred in 48 and 21% of patients, respectively, and was primarily leukocytopenia and neutropenia. Grade III and IV gastrointestinal toxicities occurred in 31 and 10% of patients, respectively. There was one death attributed to sepsis. The concurrent gemcitabine and radiation portion of the study was completed without treatment interruptions in 56% of patients. The overall median survival was 8.2 mo and the median survival in the 44% of patients demonstrating a sustained CA-19-9 response was 13.5 mo. Only six patients experienced local regional progression as their first site of failure. Two patients (5%) were still alive at 35 and 41 mo posttreatment. CONCLUSIONS: These results confirm the feasibility of twice weekly gemcitabine and radiation for the treatment of pancreatic cancer. Although this treatment strategy produced good local regional control, this did not result in a survival advantage. Stratifying patients by performance status and CA-19-9 response in future trials may be of value.

Adenocarcinoma↗
PubMed2002

Impact of T and N substage on survival and disease relapse in adjuvant rectal cancer: a pooled analysis.

PURPOSE: To determine the rates of survival and disease control by TNM and MAC stage in three randomized North American rectal adjuvant studies. MATERIALS AND METHODS: Data were merged from 2551 eligible patients on NCCTG 79-47-51 (n = 200), NCCTG 86-47-51 (n = 656), and INT 114 (n = 1695). All patients received postoperative radiation, and 96% were randomized to receive concomitant and maintenance chemotherapy. Five-year follow-up was available in 94% of patients and 7-yr follow-up in 84%. Kaplan-Meier curves were used to estimate the distribution of overall survival (OS) and disease-free survival (DFS), and p values were derived using the log-rank test. Time to local and distant relapse was estimated using cumulative incidence methodology. Analyses were adjusted for treatment effect using Cox proportional hazards models. RESULTS: OS and DFS were dependent on both TN stage and NT stage (N substage within T stage and T substage within N stage). Even among N2 patients (4 or more LN+), T stage influenced 5-yr OS (T1-2, 69%; T3, 48%; T4, 38%). Three risk groups of patients were defined: (1) intermediate: T3N0, T1-2N1; (2) moderately high: T4N0, T1-2N2, T3N1; and (3) high: T3N2, T4N1, T4N2. For Group 1, 5-yr OS was 74% and 81%, and 5-yr DFS was 66% and 74%. For Group 2, 5-yr OS ranged from 61% to 69%, and for Group 3, OS ranged from 33% to 48%. Cumulative incidence rates of local relapse and distant metastases revealed similar differences by TN and NT stage, as seen in the survival analyses. CONCLUSION: Patients with a single high-risk factor of either extension beyond the rectal wall (T3N0) or nodal involvement (T1-2N1) have improved OS, DFS, and disease control when compared to those with both high risk factors. Different treatment strategies may be indicated for intermediate- (T3N0, T1-2N1) vs. moderately high or high-risk patients in view of differential survival and rates of relapse. For future trial design, it may be preferable to perform separate studies, or a planned statistical analysis, for the "intermediate-risk" vs. the "moderately high" or "high-risk" subsets of patients.

Chemotherapy, Adjuvant↗