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A S Glicksman

Publications and source records attributed to A S Glicksman.

At least 19 recordsLinked to original sources
PubMed1998

A comparative study of the long term psychosocial functioning of childhood acute lymphoblastic leukemia survivors treated by intrathecal methotrexate with or without cranial radiation.

BACKGROUND: Although previous research has delineated medical, cognitive, and neuropsychologic late effects of central nervous system (CNS) prophylaxis for childhood acute lymphoblastic leukemia (ALL), it has been difficult to draw conclusions about the long term psychosocial sequelae of these treatments due to methodologic problems that led to inconclusive results in past studies. In the current study, the authors examined the long term psychosocial functioning of childhood ALL survivors who had been treated on a Phase III clinical protocol (Cancer and Leukemia Group B [CALGB] 7611) between 1976 and 1979, in which they were randomized to receive either 2400 centigray of cranial radiation (CRT) with intrathecal methotrexate (IT-MTX) or intermediate dose systemic methotrexate (IV-MTX) with IT-MTX. METHODS: One hundred ten survivors of childhood ALL (mean age, 20.8 years) treated on CALGB 7611 who were age 14 years or older and disease free for at least 1 year were studied a mean of 14.7 years after their entry on CALGB 7611. In a telephone interview, a psychosocial assessment battery was administered to the patients, consisting of measures that assessed psychologic, sexual, social, and vocational functioning as well as any delayed physical effects. RESULTS: Survivors who had received CRT + IT-MTX had significantly poorer academic achievement (P = 0.0001), poorer self-images with regard to their bodies (P = 0.001), and greater psychologic distress (P = 0.005). CONCLUSIONS: Cranial radiation used to treat children with ALL has significant long term sequelae in terms of poorer academic achievement and psychosocial functioning. These data add weight to the conclusion that CRT prophylaxis should only be used to treat children who are at high risk of CNS relapse.

Achievement↗
PubMed1997

Concurrent platinum-based chemotherapy and hyperfractionated radiotherapy with late intensification in advanced head and neck cancer.

PURPOSE: To determine whether a course of hyperfractionated radiation therapy concomitant with escalated radiosensitizing platinum compounds can be administered with acceptable morbidity and achieve a high rate of loco-regional control for Stage III and IV head and neck cancer and whether the patients can be tumor free at the primary site after initial therapy and cured by the additional chemoradiation without radical resection of the primary tumor. METHODS AND MATERIALS: Patients with Stage III/IV head and neck cancer were treated in this multicenter Phase II Study with 1.8 Gy fraction radiotherapy for 2 weeks, with escalation to 1.2 Gy b.i.d. hyperfractionation to 46.8 Gy. Concomitant continuous infusion cisplantinum (CDDP) 20 mg per meter square on day 1 to 4 and 22 to 25 was given. Reassessment by biopsy of primary and nodes was done. Patients with a complete response continued with hyperfractionated radiotherapy to 75.6 Gy with simultaneous carboplatinum (Carbo), 25 mg per meter square b.i.d. for 12 consecutive treatment days. Patients with residual disease at 46.8 Gy required curative surgery. Seventy-four patients were treated at the three institutions; 20 were Stage III and 54 were Stage IV. All patients had daily mouth care, nutritional, and psychosocial support. RESULTS: This regime was well tolerated. Eighty-five percent of toxicities were Grade 1 or 2 and there was only one Grade 4 hematologic toxicity. Late toxicities included xerostomia in 25 patients, dysphasia in 18, and mild speech impediment in 11. Biopsies of primary site were done after the first course of treatment in 59 patients. Neck dissections were performed in 35 patients. Forty-four of 59 (75%) primary sites and 16 of 35 (46%) lymph nodes had pathologically complete response (CR). Of the 74 patients, only 12 required surgical resection of the primary site. Thirty-five of the 50 node positive patients had neck dissections, 16 of these were CRs at surgery. At 4 years (median follow-up of 26 months), disease-specific survival is 63%. The actuarial survival for all patients is 51%. Patients with pathological CR after initial treatment have disease specific survival of 73% at 4 years vs. 48% of patients with partial response (PR) only. CONCLUSION: This study, developed on the basis of radiobiological and cell kinetic precepts, produced results that compare favorably with other reports of management of patients with advanced head and neck cancer. In comparison with our previous study, these results are comparable, not impressively better. The associated morbidity was somewhat worse.

Adult↗
PubMed1997

Low acute gastrointestinal and genitourinary toxicities in whole pelvic irradiation of prostate cancer.

PURPOSE: This retrospective study was done to determine the frequency and severity of acute gastrointestinal (GI) and genitourinary (GU) toxicity associated with whole pelvic radiotherapy of localized prostate cancer. METHODS AND MATERIALS: Between 1989 and 1994, we treated 156 patients with localized prostate cancer, ranging in age from 54 to 86 (median 71), of which 86 were older than 70 years of age. No attempt at selection was made, and many were from the Veteran's Administration Hospital where they had been precluded from their surgical program because of comorbidities and/or advanced age. Of 156 patients, 45 (28.8%) underwent pretreatment laparoscopic lymphadenectomy (LAP); 40 had negative findings. Four-field box technique was used for all patients. We treated the whole pelvis to 45 Gy, followed by a cone-down and a final boost to a total dose of 72 Gy. The cone-down to the lower pelvis and boost to the prostate were based on computed tomography and/or magnetic resonance imaging findings for volume reconstruction with field size of approximately 8 x 8 and 6 x 6 cm, respectively. Diet instructions were given before treatment and emphasized weekly. Toxicities were evaluated weekly by physicians and nurses independently using Cancer and Leukemia Group B (CALGB) grading criteria. RESULTS: The acute GI and GU toxicities gradually increased from Week 2, peaked at Week 5, and then declined after that. During Week 5, acute Grade 1-3 GI morbidities were observed in 19 (12.2%), 2 (1.3%), and 1 (0.6%) patients, respectively. Genitourinary toxicity was similar, accounting for 17 (10.9%), 6 (3.8%), and 1 (0.6%), respectively. Overall Grade 2 toxicities occurred in 30 of 156 patients (19%). Comorbidity was associated with more GI toxicity. Patients over 70 years of age tended to reach the maximal GI and GU toxicity 1-2 weeks earlier than did patients under the age of 70. Of the patients who did not follow the diet instruction, all experienced side effects. CONCLUSIONS: Whole pelvic irradiation was very well tolerated in this group of patients. The frequency of acute Grade 2 GI and GU toxicity compared favorably with the reported results of conformal treatment. Diet restriction and psychosocial input may have had a positive impact. Late sequelae will be evaluated in long-term follow-up.

Acute Disease↗
PubMed1997

Intermediate-dose methotrexate versus cranial irradiation in childhood acute lymphoblastic leukemia: a ten-year follow-up.

The cure rate of childhood acute lymphoblastic leukemia (ALL) has improved dramatically. Still there is a paucity of long-term data. With the improving cure rate, the quality of life and avoidance of second cancers have become important concerns. We evaluated 596 children and adolescents with ALL on Cancer and Leukemia Group B 7611 (CALGB 7611) who were randomized between 1976 and 1979 to receive intermediate-dose methotrexate (IDM) plus intrathecal methotrexate (IT MTX) or cranial radiation (CRT) plus IT MTX. After 10 additional years of follow-up, the pattern and significance of the results reported in 1983 are confirmed. IDM offered better hematologic protection (P < 0.0006), better testicular protection (P = 0.002), but CRT offered better central nervous system (CNS) protection (P < 0.0001). The retrieval rate for the 231 patients who relapsed while on therapy or within 6 months of elective cessation of therapy is 20 +/- 5%. For the 33 patients who relapsed more than 6 months after cessation of therapy, the retrieval rate is 49 +/- 10%. For all patients, the 12-year event-free survival was 37 +/- 3.6% and the overall survival was 49 +/- 3.5%. There were two cases of second malignancies reported in 3,502 person-years of survival. Both occurred following salvage therapy. There was no evidence of an excessive number of second primaries over the general population of children. There were no reported instances of clinical cardiopathy. After a median follow-up of 11 years, there have been no reports of cardiopathy and no evidence of an increased risk of second cancers in children treated on CALGB 7611. While the overall outcome is not what would be expected with modern therapy, one can conclude that CRT offered better CNS protection, but IDM offered better systemic and testicular protection. A small risk of second cancers or cardiac dys-function may be acceptable with therapies which produce long-term documented survival benefits.

Adolescent↗
PubMed1996

Systemic and adjuvant therapy for patients with pancreatic carcinoma.

BACKGROUND: Pancreatic cancer is a highly lethal disease with < or = 5% of patients surviving 5 years. There is no curative therapy for patients who cannot be surgically resected. Chemotherapy and radiation therapy can provide palliation but have not had a significant impact on 5-year survival. METHODS: Newer approaches for improving the survival of patients with pancreatic cancer integrating chemotherapy, radiation therapy, and surgery are being evaluated. New chemotherapeutic agents (e.g., gemcitabine, camptothecins, taxanes, thymydilate synthase inhibitors, and fluorouracil-related compounds) are being studied alone and in combination with each other or different agents (e.g., trimetrexate or platinum-related compounds). RESULTS: Increased knowledge about the biology of pancreatic cancer (including high frequency of ras and p53 mutations in neoplastic cells or the expression of a number of growth factor receptors on the cell surface) has lead to preclinical evaluation of novel approaches attempting to specifically target these. These novel approaches include gene therapy, vaccines, and antisense oligonucleotides targeted to genes important for proliferation or survival of pancreatic cancer cells. CONCLUSIONS: Continued development of new approaches is needed to improve the treatment and survival of patients with pancreatic cancer.

Chemotherapy, Adjuvant↗
PubMed1995

Hyperfractionated radiation in children with rhabdomyosarcoma--results of an Intergroup Rhabdomyosarcoma Pilot Study.

PURPOSE: The Intergroup Rhabdomyosarcoma Study (IRS) Group initiated a pilot study (IRS IV-P) of hyperfractionated radiation (HF XRT) with chemotherapy to test the feasibility and toxicity of this combined modality approach in children with localized but nonresected (group III) and metastatic (group IV) rhabdomyosarcoma. METHODS AND MATERIALS: Using the linear quadratic equation, and an alpha/beta ratio of 10 Gy for acute reacting tumor effect and 3 Gy for late reacting normal tissue effect, a HF XRT protocol was developed giving a total radiation dose of 59.4 Gy, in 1.10 Gy fractions, twice daily at 6-8 h intervals. All patients received chemotherapy in addition to irradiation. The radiation scheme was calculated to increase the biologically effective dose to the tumor by 10% without increasing late effects, when compared to a conventional schedule of 50.4 Gy in 1.8 Gy daily fractions. This protocol also was predicted to cause an increase in acute normal tissue effects. RESULTS: Four hundred forty-nine children age 21 years and younger were eligible for the hyperfractionated radiation study of whom 297 had Group III disease and 152 had Group IV disease. A total of 117 patients were excluded from the feasibility and toxicity analysis because of progressive disease or death prior to scheduled irradiation, surgical resection, major protocol violation, treatment with brachytherapy, or missing data. Thus, 332 children were evaluable for the HF XRT protocol. Twenty-eight of the 332 (8%) were given conventional radiation because of physician preference or young age. Twenty of the 332 (6%) were not irradiated because of young age, anesthesia, or transportation problems. All nonirradiated children were < or = 3 years of age. Thus, 284 children, 86% of the evaluable population, received HF XRT. The radiation dose, number of fractions, number of days, and interfractional interval were scored as appropriate in 93% of cases. Review of radiation portals revealed that in 230 of 284 cases (81%) the radiation fields were appropriate, as per protocol. Thus, the HF XRT was feasible treatment in a multiinstitutional study. Analysis of toxicity revealed that 152 of 204 (75%) of Group III and 52 of 80 (65%) of Group IV patients experienced severe or life-threatening toxicity, explained by the addition of chemotherapy with the radiation. The majority of this toxicity was hematopoietic. Observed organ toxicity, which was potentially explained by the radiation treatment, was greatest at the end of radiation, and improved at the 6-week and 3-month evaluation periods. There were no deaths attributed to radiation toxicity and no instance of toxicity that required alteration of the radiation protocol. Thus, the treatment was not associated with toxicity that was considered excessive or unusual. CONCLUSION: The IRS IV-P study confirms that HF XRT combined with chemotherapy is both feasible and tolerable in children with rhabdomyosarcoma. A prospective randomized trial is underway to test its efficacy as compared to conventional radiation among children also receiving concurrent chemotherapy for rhabdomyosarcoma.

Adolescent↗
PubMed1995

Preoperative cisplatin and accelerated hyperfractionated radiation induces high tumor response and control rates in patients with advanced head and neck cancer.

BACKGROUND: Preoperative therapy with concurrent cisplatin infusion and accelerated hyperfractionated radiation has the potential to eradicate pools of resistant cells with high-growth fraction that accumulate during standard radiation therapy. Based on preliminary data showing a high complete response rate (necessary for organ preservation) in patients with advanced squamous cell cancer of the head and neck (stages III and IV), we conducted a multi-institutional study using accelerated hyperfractionated radiation to maximize local and regional tumor control without adding toxicity. PATIENTS AND METHODS: Preoperative radiation was given in 1.8 Gy fractions for 2 weeks followed by 1.2 Gy BID hyperfractionation to 46.7 Gy. Continuous infusion of cisplatin 20 mg/m2 was given on days 1 through 4 and 22 through 25. Patients were initially assessed with panendoscopy and were subsequently reassessed with biopsy of primary site (+/- nodes). Patients with negative primary site biopsy received additional hyperfractionated radiation to 76 Gy with simultaneous carboplatin 25 mg/m2 BID for 12 consecutive days. Patients with residual disease after 47 Gy had resection of primary site and node dissection. Of 69 patients treated, 56 were T3 and T4, and 46 were N1, N2, and N3; 17 patients (25%) were stage III and 50 (72%) were stage IV; in 2 patients (3%) the stage was unknown. RESULTS: Treatment was well tolerated with no grade IV toxicities, but there were 13 patients with grade III toxicities (mucositis, dysphagia, or hematological toxicity). Biopsy specimens were taken from 84% of the patients, and 81% of the primary sites showed pathologic complete response and 49% of the lymph nodes showed a pathologic complete response. Thirty-four patients underwent curative surgery. Eleven required resection of the primary and 23 required neck dissection only. At 2 years (median followup 12 months), 44 of 69 patients (64%) have no evidence of disease, 9 are dead of disease, 9 are dead of other causes, and 6 are alive with disease. Surgical toxicities were minimal and primarily limited to fibrosis in 12 patients, edema in 8 patients, tracheoesophageal fistula in 1 patient, and delayed wound healing in 1 patient. Late toxicities included xerostomia in 22 patients, dysphagia in 17, and speech impairment in 9. CONCLUSIONS: Preoperative concurrent radiotherapy and chemotherapy provides a high level of organ preservation and local and regional control because of the high complete response rate at the primary site. A planned neck dissection with minimal morbidity ensures local/regional control, as well as providing definitive staging information. A randomized evaluation is suggested for this program.

Adult↗
PubMed1994

Concurrent cis-platinum and radiation with or without surgery for advanced head and neck cancer.

PURPOSE: This study was undertaken to assess the efficacy of concurrent cis-platinum and radiation in patients with advanced head and neck cancer and to determine if patients responding to the preoperative regimens may be cured without radical surgery. METHODS AND MATERIALS: One hundred and one patients with potentially operable Stage III and IV squamous cell carcinoma of the head and neck received 45 Gy at 1.8 Gy fractions and continuous infusion cis-platinum 20 mg/m2 over 24 h on days 1 through 4 and 22 through 25 of the radiation schedule. Three to 4 weeks later, radical surgery of the primary site and neck dissections for patients presenting with cervical adenopathy was undertaken or if a complete response had been achieved, continued with radiation to 72 Gy with another course of concurrent continuous infusion cis-platinum. RESULT: Complete and partial responses were achieved in 92% of the primary sites and 95% of the nodes. Over 80% of the patients were rendered tumor free at surgery after only the initial course of chemotherapy and radiation. There were no grade 3 or 4 toxicities from chemotherapy and radiation. Ninety-five percent of the patients who initiated treatment completed it. With a median follow-up of 41 months for all patients, 49% of the patients have survived disease free up to 9 years, independent of whether or not their primary tumors were resected or were treated definitively by further chemotherapy sensitized radiation. The disease-specific survival is 78% after 3 years with no local failures thereafter. CONCLUSION: These findings suggest that continuous infusion cis-platinum administered concurrently with radiotherapy can improve survival in advanced head and neck cancer. Patients responding to the preoperative regimen may be cured without radical surgery, which can be reserved for salvage.

Actuarial Analysis↗
PubMed1993

Combined modality therapy for stage IIIA non-small cell carcinoma of the lung.

53 patients with stage IIIA non-small cell carcinoma of the lung (NSCCL) were treated with multimodality therapy consisting of induction radiotherapy (55.8 Gy) and two cycles of concurrent chemotherapy with cisplatin, 25 mg/m2 for 4 days by continuous infusion and bolus etoposide, 100 mg/m2 on days 2 and 4 of each cycle followed by surgery and adjuvant chemotherapy. Of 53 evaluable patients, 47 achieved clinical responses (9 complete response, 38 partial response) after induction therapy for a response rate of 89%. 47 patients were resectable after induction therapy, but 8 patients refused surgery and 6 patients were not eligible for surgery based on poor pulmonary function (medical contraindications). 33 patients underwent thoracotomy and in 6 patients, resection was technically unfeasible. Thus complete surgical resection was accomplished in 27 patients. After all therapy, 28 patients achieved a complete response (53%) and 19 patients a partial response (36%). Toxicities were mild. At a maximum of 75 months (median, 28 months) of follow-up, the median survival of the entire group is 24 months. The median survival of resected patients has not been reached; their 6-year survival rate is 55%. Unresected patients survived for a median of 11 months. This multimodality regimen is well-tolerated, induces a high response and resectability rate and prolongs survival in resected patients.

Adult↗
PubMed1992

Preoperative combined chemotherapy and radiation therapy plus radical surgery in advanced head and neck cancer. Five-year results with impressive complete response rates and high survival.

Radiation therapy combined with cisplatin as a chemoradiation sensitizer (CT/RT) has been reported to enhance tumor response in squamous cell carcinoma of the head and neck. In the present study, CT/RT was used preoperatively in advanced Stage III and IV head and neck cancer. Fifty-three patients were entered prospectively into a Phase II study. Treatment consisted of 4500 cGy of radiation therapy in 5 weeks combined with cisplatin 20 mg/m2 for 4 days during weeks 1 and 4 of radiation therapy. This was followed 4 to 8 weeks later by curative surgery. Pretherapy dental care; long-term nutritional support; individualized skin, mouth, and wound care; and continuous interdisciplinary communication were integral parts of this regimen. In four patients, CT/RT toxicity was seen (8%); three episodes of skin reaction or stomatitis and three episodes of leukopenia (less than 2500/microliters), causing a delay in CT/RT treatment in one patient. Three patients died of other causes during the preoperative interval, without clinical evidence of toxicity. Fifty patients (94%) had a complete (CR) or partial response (PR) to CT/RT. Clinical CR was seen in 38 of 51 (75%) primary tumors and 21 of 27 (78%) cervical nodes. Forty-one patients (77%) underwent curative surgery. In 27 of 32 (84%) resected CR primary tumors and 16 of 18 (89%) CR metastatic nodes, the surgical specimen was microscopically free of tumor. Postoperative morbidity was 32%. Five patients (12%) required additional surgery for their complications. Perioperative mortality was 5%. Five patients had tumor recurrence: three postoperatively after clinical PR to CT/RT and two in clinical CR patients who refused further treatment after CT/RT, then had a recurrence and were salvaged surgically. No patient with a CR in both the tumor and nodes who underwent surgery had a tumor recurrence. With a follow-up of 8 years (median, 40 months), the median survival for all patients was 45 months. The 5-year actuarial survival rate was 43% for all patients and 55% for patients who had CT/RT and surgery. This multimodality treatment of advanced head and neck cancer has low toxicity and impressive survival. It renders a significant number of patients tumor-free before surgery. These patients may be candidates for additional study triaging additional CT/RT for complete CR only and surgery for PR and biopsy-proved residual disease.

Adult↗
PubMed1992

Preoperative chemotherapy and radiation therapy for stage IIIa carcinoma of the lung.

Thirty-six patients with stage IIIa histologically proven non-small cell carcinoma (T3 N2 or T2 N2) underwent concomitant radiation therapy and chemotherapy before pulmonary resection. The therapy consisted of two cycles of continuous infusion of cis-platinum, 25 mg.m-2.day-1 (days 1 through 4) every 4 weeks and concomitant irradiation, 55 Gy, of the tumor and mediastinum. Two to 3 weeks after treatment, the patients were reevaluated for thoracotomy and pulmonary resection. Five patients were found to have unresectable lesions. Thirty-one patients had complete resection, 27 by radical pneumonectomy and 4 by radical lobectomy, giving a resectability rate of 86%. Complete sterilization of lung tumor and mediastinal nodes proven histologically was achieved in 10 patients (28%) and 17 patients (47%). The 3-year survival rate is 61.7% for patients who had resection. Median follow-up is 27 months (range, 6 to 61 months). The preliminary study indicates that preoperative cis-platinum and concomitant radiation therapy is tolerated, appears to increase resectability, and may improve survival in patients with stage IIIa lung cancer.

Adult↗
PubMed1992

The structure for a radiation oncology protocol. The Committee of Radiation Oncology Group Chairmen.

Multi-institutional Cooperative Group clinical trials involving radiotherapy require unambiguous therapeutic guidelines, so that patients entered from each of the participating institutions will receive essentially uniform treatment. The technical guidelines for a Radiation Oncology Protocol presented in this report represents a consensus of the Radiotherapy Committees in the major NCI funded Cooperative Groups and is derived from over a decade of experience. Although they have been written for external beam therapy, they are applicable to brachytherapy with appropriate technical considerations. It is anticipated that further evolution will occur with the introduction of new technologies such as 3-D treatment planning and delivery, multi-leaf collimation and small field irradiation.

Clinical Protocols↗