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Biomedical subjects

H Selim

Publications and source records attributed to H Selim.

10 recordsLinked to original sources

Hyperfractionated radiotherapy and paclitaxel for locally advanced/unresectable pancreatic cancer.

PURPOSE: To determine prospectively the maximal tolerated dose and potential antitumor activity of weekly paclitaxel with concurrent hyperfractionated radiotherapy in patients with locally advanced and/or unresectable pancreatic cancer. METHODS AND MATERIALS: We embarked on Phase I-II study of hyperfractionated radiotherapy using a concomitant in-field boost to a total dose of 63.80 Gy in 6 weeks at 1.1 Gy/fraction. Paclitaxel was administered weekly on Days 1, 8, 15, 22, 29, and 36 as a 3-h infusion. Paclitaxel doses were escalated from 20 mg/m(2)/wk to 70 mg/m(2)/wk. Twenty patients were studied, 14 women and 6 men (mean age 64 years). Some patients presented with one or more symptoms. Obstructive jaundice was the main presenting symptom in 10 patients and epigastric pain in 14. All patients had unresectable histologically proven adenocarcinoma of the pancreas (15 head, 4 body, and 1 tail). Reasons for unresectability were involvement of the portal vein, and/or superior mesenteric artery (n = 14), paraaortic nodes (n = 8), and medically inoperable (n = 1). Fourteen patients underwent a biliary bypass procedure before treatment (four endoscopic stenting, five choledochojejunostomy, and five cholecystojejunostomy). The follow-up period ranged from 14 to 66 months (median 44). RESULTS: The dose-limiting toxicity was observed at 70 mg/m(2)/wk. Grade IV Radiation Therapy Oncology Group late GI toxicity was seen in 1 patient in the form of duodenal stricture and hemorrhage. Grade II gastrointestinal adverse effects occurred in 13 patients and Grade 3 in 1 patient. No neurologic morbidity was encountered. Eight patients required cytokine support for Grade 2 and 3 neutropenia. The treatment course was delivered within the planned time in 80% of the patients. Complete relief of pain occurred in 10 of 14 patients. The CA 19-9 level was either stable or decreasing in 12 of 15 patients. Of 17 assessable patients, stable disease was seen in 10, regression in 2, a partial response in 3, and a complete response in 2. CONCLUSION: The use of hyperfractionated radiotherapy to a dose of 63.80 Gy with concomitant weekly paclitaxel is tolerated. The maximal tolerated dose of paclitaxel for this study was 60 mg/m(2)/wk. The preliminary objective responses denote activity of the regimen. We recommend testing this regimen in larger scale studies.

Adenocarcinoma↗

Phase I/II trial of accelerated fractionation in brain metastases RTOG 85-28.

PURPOSE: Radiation Therapy Oncology Group 85-28 represents a Phase I/II trial of accelerated fractionation in patients with brain metastases. METHODS AND MATERIALS: Patients entered had controlled or absent primary with metastases other than brain which were stable or only brain metastases with the primary uncontrolled. Karnosfky status was required to be greater than 60. Patients received 1.6 Gy twice daily separated by 4-8 hr delivered 5 days a week. The entire brain was treated to 32.0 Gy and the boost dose escalated from 16.0 Gy to 22.40 Gy and subsequently 32.00 Gy and 42.40 Gy. RESULTS: We observed no undue toxicity with escalating dose of irradiation. An incremental, although not statistically significant improvement in survival was noted with escalating doses. Median survival ranged from 4.2 months to 6.4 months with escalating dose of irradiation. Median survival also increased in patients with controlled primary tumors, non-lung primaries and solitary metastasis. CONCLUSION: The incremental improvement in survival in patients with good prognostic factors appeared encouraging. The Radiation Therapy Oncology Group will test the 54.4 Gy study against 30 Gy in 2 weeks in a Phase III trial based on the results of this trial.

Adult↗

Improved survival duration in patients with unresected solitary brain metastasis using accelerated hyperfractionated radiation therapy at total doses of 54.4 gray and greater. Results of Radiation Therapy Oncology Group 85-28.

BACKGROUND: Although there have been occasional reports of improved response with greater doses of irradiation for unresected brain metastases, dose escalation has not been systematically studied in a cohort of patients with solitary brain metastasis. The current study examines this group of patients to evaluate dose escalation using accelerated hyperfractionated radiation therapy (XRT) with regard to survival, patterns of failure, and toxicity. METHOD: Radiation Therapy Oncology Group (RTOG) 85-28, a Phase I/II randomized trial of accelerated hyperfractionated XRT for patients with unresected supratentorial brain metastases, enrolled 153 patients with solitary brain metastasis. Whole brain dose was 32 Gray (Gy) administered in 1.6 Gy fractions twice a day with an interfraction interval of 4-8 hours. Boost dose was escalated to total doses of 48.0, 54.4, 64.0, and 70.4 Gy. RESULTS: Acute and late toxicities were acceptable. The median survival time and 1-year survival rates were 4.9 months and 20% at 48 Gy; 5.4 months and 33% at 54.4 Gy; 7.2 months and 28% at 64 Gy; and 8.2 months and 37% at 70.4 Gy, respectively. Comparison of the upper three dose treatment arms to the 48 Gy treatment arm revealed a superior survival time with doses of 54.4 Gy and greater (P = 0.05). Improvement in neurologic function appeared to increase with dose escalation, with 25% of patients experiencing improvement at doses of 48 Gy, 38% at 54.4 Gy, 50% at 64 Gy, and 63% at 70.4 Gy (P = not significant). CONCLUSION: A radiation dose response for survival time appears to exist with the use of accelerated hyperfractionated XRT for patients with unresected solitary brain metastasis.

Adenocarcinoma↗

Comparison of the Radiation Therapy Oncology Group and American Joint Committee on Cancer staging systems among patients with non-small cell lung cancer receiving hyperfractionated radiation therapy. A report of the Radiation Therapy Oncology Group protocol 83-11.

Since 1973, the Radiation Therapy Oncology Group (RTOG) has staged and stratified patients in non-small cell lung cancer (NSCLC) protocols according to the RTOG staging system. In 1985, the American Joint Committee on Cancer (AJCC) revised its lung cancer staging system, with the principle differences from the RTOG system being the staging of involvement of the chest wall and of contralateral mediastinal and hilar lymph nodes. To determine if the AJCC system discriminated outcome differently than the RTOG system in a nonoperative series, all 850 evaluable patients treated with hyperfractionated radiation therapy (RT) on the RTOG protocol 83-11 were restaged by the AJCC system. There was 67% agreement in patient distribution between the following comparable stages in each system: RTOG Stage II/AJCC Stage II; RTOG Stage III/AJCC Stage IIIA; and RTOG Stage IV/AJCC Stage IIIB. Both systems successfully predicted for survival (P less than 0.001), although the RTOG staging was more discriminating (relative risk ratios, 1.59 versus 1.38). Among the 507 favorable patients (those with less than or equal to 5% weight loss and Karnofsky performance status [KPS] of 70 to 100), the RTOG staging was also more predictive (P = 0.004 versus P = 0.01). When RTOG Stage III (462 patients) was divided into those without contralateral mediastinal or hilar adenopathy (AJCC Stage II/IIIA) and those with (AJCC Stage IIIB), a significant survival (P = 0.0001) was noted with 2-year survival rates of 26% versus 4%, respectively. When AJCC Stage IIIA (348 patients) was divided into the patients without chest wall invasion (RTOG Stage II/III) and those with (RTOG Stage IV), a difference in 2-year survival of 22% versus 10% was observed (P = 0.002). Although both staging systems independently predict for survival, a fusion of both staging systems is the most discriminating of outcome. Future nonoperative studies in locally advanced NSCLC should stratify for contralateral nodal involvement (per AJCC staging) and chest wall invasion (per RTOG staging).

Carcinoma, Non-Small-Cell Lung↗

ASTRO plenary: interfraction interval is a major determinant of late effects, with hyperfractionated radiation therapy of carcinomas of upper respiratory and digestive tracts: results from Radiation Therapy Oncology Group protocol 8313.

A prospective, randomized, multi-institutional, Phase I(LE)/II trial of HFX was conducted by the RTOG between 1983 and 1987. Patients with histologically proven, inoperable squamous cell carcinoma of the upper respiratory and digestive tracts stratified by site, nodal status, and performance status, were assigned to one of three arms, were assigned to one of three arms, 67.2 Gy, 72.0 Gy, or 76.8 Gy. Fractions of 1.2 Gy were given twice daily, 5 days per week: intervals of 4 to 8 hours were permitted between fractions. After acceptable rates of acute normal tissue effects were found, the randomization was changed to evaluate a new higher total dose, 81.6 Gy. Of 479 patients entered, 447 were analyzed, 63 on 67.2 Gy, 129 on 72.0 Gy, 117 on 76.8 Gy, and 138 on 81.6 Gy. The treatment arms were well balanced with respect to pretreatment characteristics. Acute reactions consisted almost entirely of pseudomembranous inflammation. "Severe" (Grade 3) acute reactions were reported in 33% to 41% and grade 4 reactions were found in 0 to 3% of patients, with no differences in frequencies among the four arms. Toxicities that developed or persisted beyond 90 days after the first treatment (408 patients evaluable greater than 90 days) did not differ among arms: grade 3+ reactions occurred in 10% to 14%, and grade 4+ effects (necroses) were reported in 5% at 67.2 Gy, 3% at 72.0 Gy, 7% at 76.8 Gy, and 2% at 81.6 Gy. Grade 3+ acute reactions occurred in 40% of patients when the interfraction interval was less than or equal to 4.5 hours versus 31% with greater than 4.5 hours (p = .03). Interfraction intervals less than or equal to 4.5 hours were associated with higher frequencies of grade 4+ late effects in all four arms, 8% of 197 patients with less than or equal to 4.5 hours versus 1% of 211 patients with greater than 4.5 hours. Estimates of late toxicity at 1, 2, and 3 years were 5.5%, 9.8%, and 15.4% with intervals less than or equal to 4.5 hours, versus 1.7% at all three periods for greater than 4.5 hours (p = .006). Local-regional control at 2 years was 25% for the assigned dose of 67.2 Gy compared to 43% to 45% for the three higher doses (p = .01), but a similar comparison for survival showed no significant difference (p = .35). There was no evidence for an effect of interfraction interval on either local-regional control (p = .38) or survival (p = .28).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Recurrent tumors of the head and neck, pelvis, and chest wall: treatment with hyperthermia and brachytherapy.

Cancer that recurs after surgery and radiation therapy remains a major problem. The claimed effectiveness of thermobrachytherapy in patients with this problem prompted the present study. Forty-six lesions (20 head and neck, 18 pelvic, seven chest wall, and one limb sarcoma) in 38 patients were treated with interstitial hyperthermia that sandwiched the use of Ir-192 with the aim of delivering 2,000-6,000 cGy, depending on prior dose and tissue tolerance. Complete regression occurred in 19 (54%) of 35 evaluable cases. More than 58,000 measured temperature points were analyzed to develop a representative quantitative measure, the "modal thermal dose," that represented the temperature reported most often during heating sessions. The pattern was plotted in each case. No significant relation was found between heating patterns and tumor response. Of all the prognostic factors studied, the radiation dose was the most significant, with a complete response rate being 78% when the total radiation dose exceeded 6,000 cGy, compared with 8% when the dose was lower than 5,000 cGy (P less than .005). The tumor volume also was important, with smaller lesions responding much better than larger ones (P = .1).

Brachytherapy↗

Changes in T-cell subsets after radiation therapy.

The T-cell subsets of 129 patients with cancer were counted before and after radiation therapy. The cells were labeled with monoclonal antibodies that were specific for each type of T cell. Significant changes after therapy were decreases in the proportion of T-helper/inducer cells, pan-T cells, and in the ratio of T-helper/inducer to T-suppressor/cytotoxic cells. There was an increase in the percentage of T-suppressor/cytotoxic cells. When the site of the primary cancer was considered, genitourinary cancer and cancer of the head and neck both showed a decreased percentage of T-helper/inducer cells and a reduced ratio of T-helper/inducer to T-suppressor/cytotoxic cells. The percentage of pan-T cells in head and neck cancer and the ratio of T-helper/inducer to T-suppressor/cytotoxic cells in breast cancer were decreased. The percentage of T-helper cells was particularly decreased by radiation therapy in advanced stages of cancer, in higher grade tumors, and in larger tumors. The absolute numbers of various T-cell subsets were decreased in all groups.

Antibodies, Monoclonal↗