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ABSTRACT: Randomized trials of chemoradiation for esophageal cancer have included very few patients age > or = 75. In this retrospective study, we describe the outcomes and toxicity of full-dose chemoradiation in elderly patients with esophageal cancer. Patients, age > or = 75, treated with full-dose chemoradiation for esophageal carcinoma from 2002 to 2008 were retrospectively reviewed. Thirty-four patients were identified with a median age of 79.5 (range 75-89). The median Eastern Cooperative Oncology Group performance status was 1 (range 0-3) and the median Adult Comorbidity Evaluation-27 score was 1 (range 0-3). Twenty-eight patients received definitive and six received neoadjuvant chemoradiation. The median radiation dose delivered was 50.4 Gray (range 3.6-68.4 Gray). Platinum-based chemotherapy was used in 79.4% of patients. Fifty percent of the patients completed all planned radiation therapy (RT) and chemotherapy; 85.3% completed RT. Acute toxicity > or = grade 4 occurred in 38.2% of patients, and 70.6% of the patients required hospitalization, emergency department visit, and/or RT break. Median follow-up was 14.5 months among 7 survivors, and median survival was 12.0 months (95% confidence interval [CI]: 9.7 to 24.1 months). The actuarial overall survival at 2 years was 29.7% (95% CI: 16.6 to 52.6%). There were four treatment-related deaths. The median time to any recurrence was 10.4 months. Nineteen patients had a local and/or distant recurrence. In conclusion, elderly patients experienced substantial morbidity from chemoradiation, and long-term survival was low. Future efforts to improve treatment tolerability in the elderly are needed.
Diseases of the Esophagus 09/2009; 23(4):316-23. · 1.81 Impact Factor
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M M Fitzek,
A F Thornton,
G Harsh,
J D Rabinov,
J E Munzenrider,
M Lev, M Ancukiewicz,
M Bussiere,
E T Hedley-Whyte,
F H Hochberg,
F S Pardo
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ABSTRACT: The role of dose escalation with proton/photon radiotherapy in lower-grade gliomas was assessed in a prospective Phase I/II trial. We report the results in terms of local control, toxicity, and survival.
Twenty patients with Grade 2/4 (n = 7) and Grade 3/4 (n = 13) gliomas according to the Daumas-Duport classification were treated on a prospective institutional protocol at Massachusetts General Hospital/Harvard Cyclotron Laboratory between 1993 and 1996. Doses prescribed to the target volumes were 68.2 cobalt Gray equivalent (CGE, 1 proton Gray = 1.1 CGE) to gross tumor in Grade 2 lesions and 79.7 CGE in Grade 3 lesions. Fractionation was conventional, with 1.8 to 1.92 CGE once per day. Eligibility criteria included age between 18 and 70 years, biopsy-proven Daumas-Duport Grade 2/4 or 3/4 malignant glioma, Karnofsky performance score of 70 or greater, and supratentorial tumor. Median age of the patient population at diagnosis was 35.9 years (range 19-49). Ten tumors were mixed gliomas, one an oligodendroglioma.
Five patients underwent biopsy, 12 a subtotal resection, and 3 a gross total resection. Median interval from surgery to first radiation treatment was 2.9 months. Actuarial 5-year survival rate for Grade 2 lesions was 71% as calculated from diagnosis (median survival not yet reached); actuarial 5-year survival for Grade 3 lesions was 23% (median 29 months). Median follow-up is 61 months and 55 months for 4 patients alive with Grade 2 and 3 patients alive with Grade 3 lesions, respectively. Three patients with Grade 2 lesions died from tumor recurrence, whereas 2 of the 4 survivors have evidence of radiation necrosis. Eight of 10 patients who have died with Grade 3 lesions died from tumor recurrence, 1 from pulmonary embolus, and 1 most likely from radiation necrosis. One of 3 survivors in this group has evidence of radiation necrosis.
Tumor recurrence was neither prevented nor noticeably delayed in our patients relative to published series on photon irradiation. Dose escalation using this fractionation scheme and total dose delivered failed to improve outcome for patients with Grade 2 and 3 gliomas.
International Journal of Radiation OncologyBiologyPhysics 10/2001; 51(1):131-7. · 4.11 Impact Factor
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ABSTRACT: To evaluate our policy of performing neck dissection based on regional response after definitive radiotherapy in patients with supraglottic carcinoma and to identify the prognostic factors in this group of patients.
Between 1970 and 1995, 121 patients with node-positive squamous cell carcinoma of the supraglottic larynx were treated with definitive radiotherapy. Sixty-nine percent of patients presented with 1997 AJCC Stage IV disease. The N-stage distribution was N1, 49; N2, 62; and N3, 10. The median size of the lymph nodes was 3 cm (range, 0.5-8 cm). Forty-five patients received once-a-day treatment with a median total dose of 65 Gy (range, 58.0-70.8 Gy) in 1.8-2.0 Gy per fraction over 48 days, and 76 patients received split-course accelerated hyperfractionation with a median total dose of 67.2 Gy (range, 63.2-73.6 Gy) in 1.6 Gy twice a day over 43 days. Patients whose lymph nodes were not clinically detectable at 4-6 weeks after the completion of radiotherapy (complete response) were followed without any neck dissection. Patients with persistent neck adenopathy (partial response) underwent neck dissection whenever possible. Mean follow-up of the living patients was 6.5 years.
Regional response was related to the size of lymph nodes at presentation. Eighty-seven percent of patients with nodal size of 3 cm or less had a complete response, whereas 43% of patients with nodal size greater than 3 cm had a partial response. The rate of regional control at 3 years for all patients in the study was 66%. The 3-year ultimate regional control rate after salvage neck dissection was 75%. A relapse in both the primary and regional sites was the most common pattern of relapse, accounting for 39% of all the failures. Local failure was associated with subsequent regional relapse with a relative risk of 4.3. For patients with complete response in whom postradiotherapy neck dissection was withheld, the regional control rates were 75% and 86% for N1 and N2, respectively. The rate of isolated regional relapse in this group of patients was 7.5%. In multivariate analysis, significant favorable factors predictive for regional control were female gender, accelerated hyperfractionation, and complete response; whereas factors predictive for overall survival were Karnofsky Performance Scale score and regional response. The rate of Radiation Therapy Oncology Group (RTOG) Grade 2 or 3 neck fibrosis was 17% and 23% for patients with and without postradiotherapy neck dissection, respectively.
Isolated regional relapse is not common in patients with supraglottic carcinoma when a complete response is achieved at 4-6 weeks after definitive radiotherapy and postradiotherapy neck dissection is not performed. Female gender, accelerated hyperfractionation, and complete response are favorable predictors of regional control.
International Journal of Radiation OncologyBiologyPhysics 07/2001; 50(2):367-75. · 4.11 Impact Factor
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ABSTRACT: This study assesses the long-term outcome of patients with retroperitoneal sarcoma treated by preoperative external beam radiotherapy, resection, and intraoperative electron beam radiation (IOERT).
From 1980 to 1996, 37 patients were treated with curative intent for primary or recurrent retroperitoneal soft tissue sarcoma. All patients underwent external beam radiotherapy with a median dose of 45 Gy. This was followed by laparotomy, resection, and IOERT, if feasible. Twenty patients received 10-20 Gy of IOERT with 9-15 MeV electrons. These patients were compared to a group of 17 patients receiving preoperative irradiation without IOERT.
The 5-yr actuarial overall survival (OS), disease-free survival, local control (LC), and freedom from distant disease of all 37 patients was 50%, 38%, 59%, and 54%, respectively. After preoperative irradiation, 29 patients (78%) underwent gross total resection. For 16 patients undergoing gross total resection and IOERT, OS and LC were 74% and 83%, respectively. In contrast, these results were less satisfactory for 13 patients undergoing gross total resection without IOERT. For these patients, OS and LC were 30% and 61%, respectively. Four patients experienced treatment-related morbidity.
In selected patients, IOERT results in excellent local control and disease-free survival with acceptable morbidity.
International Journal of Radiation OncologyBiologyPhysics 06/2001; 50(1):127-31. · 4.11 Impact Factor
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ABSTRACT: To update and summarize the experience at the Massachusetts General Hospital of a treatment program of high-dose preoperative irradiation, surgical re-resection, and intraoperative radiation therapy (IORT) as a salvage treatment for patients with recurrent rectal or rectosigmoid carcinoma.
From June 1978 to February 1997, the records of 69 patients with locally recurrent rectal carcinomas or rectosigmoid carcinomas without metastases referred for consideration of IORT were reviewed. Forty-nine patients received IORT and local control and disease-free survival curves were calculated using the actuarial method of Kaplan-Meier.
The 5-year overall survival, local control and disease-free survival rates of 49 patients receiving IORT were 27, 35, and 20%, respectively. Thirty-four patients who underwent a macroscopic complete resection had a significantly better 5-year overall survival than the remaining 15 patients with gross residual disease (33 vs. 13%, P=0.05, log rank). For those patients, local control and disease-free survival rates were 46 and 27%, respectively. Patients with a microscopic complete resection had a superior 5-year overall survival than partially resected patients (40 vs. 14%, P=0.0001, log rank). Chemotherapy had no significant influence on overall or disease-free survival.
The current analysis shows the importance of a microscopic complete resection in a multi-modality approach with IORT for survival and local control. Salvage is rare for patients undergoing subtotal resection.
Radiotherapy and Oncology 02/2001; 58(1):83-7. · 5.58 Impact Factor
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C G Lee,
M Heijn,
E di Tomaso,
G Griffon-Etienne, M Ancukiewicz,
C Koike,
K R Park,
N Ferrara,
R K Jain,
H D Suit,
Y Boucher
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ABSTRACT: Recent studies in experimental animals have shown that combining antiangiogenic therapy with radiation can enhance tumor response. Whether this enhancement is mainly attributable to angiogenesis inhibition, endothelial cell radiosensitivity, tumor cell apoptosis, or a decrease in the number of hypoxic cells (improved oxygenation) is not known. We designed this study to discern the role of tumor oxygenation. We chose an anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody (mAb) which has a known target, human VEGF. We also measured interstitial fluid pressure (IFP) to test the hypothesis that the decreased vascular permeability induced by the anti-VEGF mAb can lower IFP. The effect of anti-VEGF mAb on vascular density, partial oxygen tension (pO2), and apoptosis was also measured. Athymic NCr/Sed nu/nu mice bearing 6-mm xenograft of the human glioblastoma multiforme (U87), or colon adenocarcinoma (LS174T) were treated with anti-VEGF mAb injected i.p. on alternate days for a total of six injections at a dosage of 100 microg/injection/mouse. For combined anti-VEGF and radiation, single radiation doses were given under normal blood flow (20 and 30 Gy) or clamped hypoxic conditions (30 and 40 Gy) 24 h after the sixth injection of mAb. The inhibition of the growth of U87 and LS174T tumors by the anti-VEGF mAb was associated with a significant reduction in tumor vascular density and a relatively small increase in the number of apoptotic cells. Compared with size-matched controls, IFP decreased by 74% in LS174T, and 73% in U87 in mice treated with anti-VEGF mAb. After antibody treatment PO2 increased significantly in U87, but did not change in LS174T tumors. Combined treatment induced in U87 tumors a tumor-growth delay (TGD) which was greater than additive; in LS174T except for the 40-Gy hypoxic group, the effect was only additive. In both U87 and LS174T the TGD induced by the antibody was independent of oxygen levels in the tumor at the time of radiation. The fact that the increase in TGD occurred under both normoxic and hypoxic conditions suggests that anti-VEGF mAb treatment can compensate for the resistance to radiation induced by hypoxia.
Cancer Research 11/2000; 60(19):5565-70. · 7.86 Impact Factor
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ABSTRACT: To determine the patterns of relapse and the prognostic factors for adult medulloblastomas treated in the magnetic resonance imaging era.
Between 1986 and 1996, 32 adult patients (age, > or =16 yr) with medulloblastomas confined to the craniospinal axis were treated in our institutions. Twenty cases involved classic histological features and 12 involved the desmoplastic variant. The Chang staging distribution was as follows: T1, 2; T2, 17; T3, 10; T4, 3; M0, 24; M1, 1; M2, 4; M3, 3. Brainstem invasion was present in nine patients. Lesions were midline in 13 cases and lateral in 19. Resection was complete in 17 cases, subtotal in 6, and partial in 5, with biopsy only in 4 cases. All patients received postoperative radiotherapy, with median doses of 36 Gy to the entire craniospinal axis and 55 Gy to the posterior fossa. Twenty-four patients received chemotherapy (20 before radiotherapy, 3 after radiotherapy, and 1 before and after radiotherapy).
With a median follow-up period of 5.4 years, 17 patients experienced recurrences. At 5 and 8 years, overall survival rates were 83 and 45% and disease-free survival rates were 57 and 40%, respectively. The 5- and 8-year posterior fossa control rates were 67 and 59%, respectively. Twenty-nine percent of all relapses occurred more than 5 years after treatment. The posterior fossa was the most common site of relapses. In univariate analyses, factors adversely affecting posterior fossa control were less than complete resection (P<0.001), the presence of brainstem invasion (P = 0.02), and the use of chemotherapy (P = 0.03). The overall radiotherapy duration was marginally significant in predicting posterior fossa control, with 5-year posterior fossa control rates of 81 and 49% for durations of less than 48 days and 48 days or more, respectively (P = 0.06). In a multivariate analysis, complete resection was predictive of improved posterior fossa control (P = 0.02) and disease-free survival (P = 0.02) rates. Of the eight low-risk patients who received radiotherapy alone, three experienced recurrences in the bone as the only site of relapse.
Late relapse is common among adult patients with medulloblastomas, and long-term follow-up monitoring is important. Because of the high risk of systemic failure among the low-risk patients treated with radiotherapy alone, the role of chemotherapy for this group of patients needs to be further investigated. Complete resection, the absence of brainstem invasion, and an overall radiotherapy duration of less than 48 days are important prognostic factors.
Neurosurgery 10/2000; 47(3):623-31; discussion 631-2. · 2.79 Impact Factor
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ABSTRACT: The long-term outcomes of patients undergoing local excision with or without pelvic irradiation were examined to define the role of adjuvant irradiation after local excision of T1 and T2 rectal cancers.
Ninety-nine patients with T1 or T2 rectal cancers underwent local excision with or without adjuvant irradiation at Massachusetts General Hospital and Emory University Hospital between January 1966 and January 1997. Of these, 52 patients were treated by local excision alone and 47 patients by local excision plus adjuvant irradiation. Twenty-six of these 47 patients were treated by irradiation in combination with 5-fluorouracil chemotherapy. The outcomes of these groups were compared.
The 5-year actuarial local control and recurrence-free survival rates were 72% and 66%, respectively, for the local excision alone group and 90% and 74%, respectively, for the adjuvant irradiation group. This improvement in outcome was evident despite the presence of a higher-risk patient population in the adjuvant irradiation group. Adverse pathologic features such as poorly differentiated histology and lymphatic or blood vessel invasion decreased local control and recurrence-free survival rates in the local excision only group. Adjuvant irradiation significantly improved 5-year outcomes in patients with high-risk pathologic features. Four cases of late local recurrence were seen at 64, 72, 86, and 91 months in the adjuvant irradiation group.
The authors recommend adjuvant chemoradiation for all patients undergoing local excision for T2 tumors, and for T1 tumors with high-risk pathologic features. The four cases of late local failures beyond 5 years in the adjuvant irradiation group underscores the need for careful long-term follow-up in these patients.
Annals of Surgery 08/1999; 230(1):49-54. · 7.49 Impact Factor
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ABSTRACT: To further define the indications for postoperative pelvic irradiation and chemotherapy, an analysis of the influence of extent of tumor invasion into perirectal fat, lymphatic or venous vessel invasion, and tumor grade on the clinical course of patients with Stage T3N0 rectal cancer undergoing surgery was undertaken.
From 1968 to 1985, 117 patients with Stage T3N0 rectal cancer underwent resection with curative intent. No patient received neoadjuvant or adjuvant irradiation or chemotherapy. Surgical specimens were assessed for maximum depth of tumor invasion into perirectal fat, lymphatic or venous involvement, and tumor grade. After surgery the clinical course of these patients was assessed for local control, distant metastases, and survival rate.
For 25 patients with tumors exhibiting favorable histologic features (well-differentiated or moderately well-differentiated carcinomas invading less than 2 mm into perirectal fat, without lymphatic or venous vessel involvement), the ten-year actuarial rates of local control and recurrence-free survival were 95 and 87 percent, respectively. In contrast, the ten-year actuarial rates of local control and recurrence-free survival were inferior (71 and 55 percent, respectively) for 88 patients with tumors exhibiting moderate to deep perirectal fat invasion, vessel involvement, or poor differentiation.
In the design of future trials of rectal cancer, selection of patients with rectal cancer for postoperative adjuvant therapy should be based not only on stage, but also on depth of invasion into the perirectal fat, vessel involvement, tumor grade, and integrity of the radial resection margin. For subsets of patients with Stage T3N0 rectal cancer, there may be little benefit to adjuvant therapy after surgery.
Diseases of the Colon & Rectum 03/1999; 42(2):167-73. · 3.13 Impact Factor
