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W F Regine

Publications and source records attributed to W F Regine.

At least 37 records · Page 2Linked to original sources
PubMed1998

Adjuvant therapy for pancreatic cancer: back to the future.

PURPOSE: The role of adjuvant therapy in the management of pancreatic cancer, resected with curative intent, remains controversial. This editorial review updates the status of adjuvant therapy in this context and introduces the first North American co-operative group study in this arena in roughly 20 years. RESULTS: To the extent that there has been a "standard" of care in this context, it has been defined in large part by the early work of the Gastrointestinal Study Group (GITSG). Their trial was activated in the mid 1970's using split course radiation therapy and bolus 5-FU. In the intervening 20 + years the morbidity/mortality of pancreaticoduodenectomy (PDD) has been dramatically reduced; concurrently, understanding of prognostic factors impacting on outcomes for resected patients has been significantly enhanced. In major centers the mortality of PDD is roughly 1% and survival has been shown to correlate with a number of factors including tumor size, nodal involvement, and margin status. With currently available techniques doses of continuous course radiation therapy in the range of 50-55 Gy to sites of pancreatic tumor resection and adjacent lymph node regions have been given in a number of trials with acceptable morbidity. 5-FU sequencing and administration have been advanced and gemcitabine, an agent with clear radiosensitizing properties, has been approved for use against pancreatic cancer. CONCLUSIONS: Following PDD increasing numbers of physiologically intact patients are confronting the survival statistics associated with resected pancreatic cancer. Their interest in improved therapeutic outcomes, combined with the noted improvements in radiation and chemotherapeutic management, has set the stage for renewed and intensified study. Accordingly, the intergroup mechanism of the Cancer Therapy and Evaluation Program (CTEP) of the NCI has designed, approved, and activated a modern Phase III, adjuvant protocol incorporating recently gained knowledge in this management context. Prospective randomization will be utilized to compare gemcitabine and 5-FU as single agents before and after chemoradiotherapy with 5-FU. Successful and timely completion of this newly activated intergroup study, RTOG 97-04, will establish a current, cooperative group experience, data base, and standard in the context of adjuvant therapy for pancreatic cancer and serve to provide momentum for further studies.

Antimetabolites, Antineoplastic↗
PubMed1998

High-dose preoperative radiation and the challenge of sphincter-preservation surgery for cancer of the distal 2 cm of the rectum.

PURPOSE: Sphincter-preserving surgery for the management of distal rectal cancer is gaining recognition as an alternative to abdominoperineal resection and loss of anal function. The use of high-dose preoperative radiation appears to enhance the options for sphincter preservation, even in the most distal segments of the rectum. MATERIALS AND METHODS: Seventy patients with tumors located in the distal 2 cm of the rectum received a minimum dose of 40 to 45 Gy over 4 1/2 weeks at 1.8 to 2.5 Gy per fraction. Patients with unfavorable tumors were given an additional boost of 10 to 15 Gy. Surgery was performed 5 to 10 weeks following completion of radiation. Radical surgical resection was performed in 48 patients and full thickness local excision in 22. Follow-up ranged from a minimum of 1 year to a maximum of 10 years, with a median of 4 years. RESULTS: There was one perioperative mortality. Two patients did not have their colostomy closed because of complications. Late diversion was required in 4 patients, primarily for recurrent disease. Sixty patients (86%) maintained long-term satisfactory sphincter function. Local recurrence was observed in 9 patients (13%) and distant metastases in 12 patients (17%). The overall five-year actuarial survival rate was 82%. The 5-year survival and local recurrence for postradiation pathological stage of disease was: T0, T1, T2, N0--95% and 8%, T3, T4, N0--91% and 4%, T(any) N+--50% and 41%, respectively. CONCLUSION: High-dose preoperative radiation, in properly selected patients with rectal cancers of the distal 2 cm, offers opportunities for sphincter-preserving surgical resection with excellent local control, survival, and enhanced quality of life.

Adult↗
PubMed1998

Evolving trends in combined modality therapy for pancreatic cancer.

Only 5%-15% of patients with pancreatic adenocarcinoma undergo potentially curative resection. Evidence that postoperative adjuvant therapy improves outcome is limited to a single randomized trial utilizing split-course chemoradiation. More aggressive regimens have developed and are associated with, at best, a modest improvement in patient outcome. The potentially significant morbidity associated with pancreaticoduodenectomy, which can compromise the delivery of postoperative chemoradiation, has led to the investigations of preoperative regimens. Although such an approach is feasible, its ultimate impact warrants further evaluation. Among the 4% of patients who present with unresectable or locally advanced disease, combined modality therapy has produced the most promising results. However, only modest improvements in survival have so far been achieved. Combined modality therapy with radioisotope implantation appears to have the greatest potential for improving local control and survival in these patients. Intraoperative radiation therapy (IORT) may be associated with lower morbidity than radioisotope implantation, but its impact may be limited by radiobiological disadvantage associated with single-dose boost therapy. The problem of distant metastasis remains significant. New chemotherapeutic agents have the potential to produce better results than those achieved with 5-fluorouracil. Continued advances in surgery, radiation, and systemic therapy should lead to the increased use of modern combined modality interventions with an associated further improvement in patient outcome.

Adenocarcinoma↗
PubMed1998

Multiple causes of cerebrovascular events in children with tumors of the parasellar region.

Cerebrovascular arterial occlusion is a rare but devastating event causing long-term morbidity in children with tumors in the parasellar region. While usually associated with radiation therapy, there are a variety of host, tumor and treatment factors which predispose patients to significant vasculopathy. Case reports of 5 patients from St. Jude Children's Research Hospital with tumors in the parasellar region who presented with or developed vascular occlusive disease are summarized. Multiple factors are identified in these cases which probably impacted on the development of cerebral arterial occlusion with or without moyamoya syndrome. These include, but are not limited to, neurofibromatosis, tumor encasement of major cerebral vessels, surgical alterations, and radiation therapy. The literature supports multiple, potentially interactive etiologies for the development of vascular events in these patients, suggesting that their development is not simply a phenomenon related to radiation therapy.

Brain Neoplasms↗
PubMed1998

Intracranial germinoma: treatment with radiosurgery alone--a case report.

The management of intracranial germinomas is controversial, with treatment options including conventional wide-field irradiation with or without chemotherapy or primary chemotherapy alone. The potential role of radiosurgery in the treatment of these lesions, although appealing, remains to be defined. We report a case whose initial management plan included radiosurgery to be followed by chemotherapy; however the patient subsequently refused chemotherapy. The presentation, diagnosis, treatment and results are discussed.

Adult↗
PubMed1998

Second malignant neoplasia in patients with T1 glottic cancer treated with radiation.

OBJECTIVE/HYPOTHESIS: To evaluate incidence, site of occurrence and outcome of second malignant neoplasia (SMN) in patients with T1 glottic cancer treated with radiation. STUDY DESIGN: Retrospective. METHODS: Between February 1964 and May 1993, 158 patients with T1 squamous carcinoma of the larynx were treated with definitive radiation. Incidence, site (aerodigestive tract or not) and outcome of SMN were analyzed. Median follow-up was 63 months (range, 12-245 mo). RESULTS: Thirty-four patients developed SMN, for an overall incidence of 22%. Twenty-four (67%) SMNs occurred in an aero-upper-digestive-tract site compared with nine (25%) occurring in a non-aero-upper-digestive tract site. The incidence of SMN observed was higher than would be expected for the general population at risk. The observed-to-expected ratios (OER) for all SMN, aero-upper-digestive SMN and non-aero-upper-digestive SMNs were 1.73, 5.53, and 0.62, respectively. Overall 5- and 10-year survivals were 76% and 57%, respectively, for those who did not develop SMN, as compared with 68% and 26%, for those who developed SMN (P = .003). Overall, 13 patients (8.2%) have died from laryngeal cancer, while 23 (15%) died from SMN (P = .001). CONCLUSION: This study confirms a higher incidence of SMN in T1 glottic cancer patients, compared with the general population. The majority of cases occur in aero-upper-digestive sites. These patients are more likely to die from their SMN than from glottic cancer. Patients with T1 squamous cell carcinoma of the glottic larynx represent a group of head and neck cancer patients who should be targeted in studies evaluating the potential benefits of chemoprevention, and aggressively counseled for social and/or behavioral modifications.

Carcinoma, Squamous Cell↗
PubMed1998

Thyroid lymphoma: is there a role for surgery?

The role of surgery in the treatment of Stage I and II non-Hodgkin's thyroid lymphoma (NHTL) is not well defined. At our institution, we have treated seven patients (six women and one man) with NHTL during the past 6 years. Three patients (43%) had a prior history of thyroid disease, usually lymphocytic thyroiditis. Clinical symptoms included a rapidly enlarging neck mass (86%), dysphagia (71%), dyspnea (71%), and hoarseness (71%). Five patients (71%) had hypothyroidism; one patient, hyperthyroidism; and one patient, normal thyroid function. Five patients underwent fine-needle aspiration (FNA) at our institution. In three instances, FNA results were indicative of NHTL; the remaining FNA tests yielded no diagnosis. Surgical procedures were varied: incisional biopsy (n = 4), limited tumor debulking with tracheostomy (n = 2), and thyroidectomy (n = 1). Each of the seven patients was found to have large cell lymphoma. Treatment consisted of combination chemotherapy with consolidative irradiation. All tumors dramatically decreased in size soon after the initiation of therapy. One patient refused radiotherapy. All patients except one are still alive (median follow-up, 24 months). In conclusion, 1) a diagnosis of NHTL, although rare, should be considered when patients have rapidly growing goiters; 2) FNA is a useful first step in diagnosing NHTL; 3) NHTL is exquisitely sensitive to both chemotherapy and radiation; 4) surgical intervention is generally confined to incisional biopsy with occasional limited pretracheal tumor debulking; and 5) when a biopsy is obtained from a patient suspected of having NHTL, immediate processing by the pathologist is recommended so that material can be obtained for special studies as needed.

Aged↗
PubMed1997

Efficacy of postoperative radiation therapy for recurrent squamous cell carcinoma of the head and neck.

PURPOSE: Postoperative radiation therapy (RT) following surgical resection is often the recommended treatment for recurrent squamous cell carcinoma (SCC) of the head and neck. Despite common use, there are few published series evaluating such a management approach. METHODS AND MATERIALS: We evaluated the efficacy of postoperative RT in 31 patients with recurrent SCC of the head and neck treated between 1981 and 1993. None of the patients had prior RT. All had complete resection of recurrent gross disease and no distant metastases. Maximum postoperative RT doses ranged from 59.4-70 Gy (median = 66 Gy). RESULTS: The 5-year disease-specific survival (DSS) and local control (LC) rate for all patients were 32 and 46%, respectively. Several prognostic factors were analyzed including site and stage of original primary tumor, disease-free interval, site of recurrence, status of surgical margins, and dose. Only site of recurrence significantly influenced both DSS and LC. Patients whose recurrence was limited to previously undissected tissue had 5-year DSS and local control rates of 60 and 74%, respectively, as compared to 19 and 29%, respectively, for patients whose recurrence was within previously dissected tissue (p = 0.05). CONCLUSIONS: Patients with recurrent SCC of the head and neck treated with standard postoperative RT following surgical resection do relatively well if the recurrence is within previously undissected tissue (i.e., nodal only); however, patients whose recurrence is within previously dissected tissue do poorly. Every effort to prevent locoregional disease recurrence at the time of primary therapy should be emphasized.

Adult↗
PubMed1997

Efficacy of targeted supradose cisplatin and concomitant radiation therapy for advanced head and neck cancer: the Memphis experience.

PURPOSE/OBJECTIVE: To evaluate the feasibility, response rates, and toxicity of a Phase II study using targeted supradose cisplatin and concurrent radiation therapy in unresectable Stage III-IV head and neck squamous cell carcinoma. METHODS AND MATERIALS: Sixty patients presenting between 6/93-9/94 were enrolled, 44 (73%) of whom had T4 and/or N2-N3 nodal disease. All patients were treated with rapid targeted superselective intraarterial infusions of cisplatin (150 mg/m2 weekly x 4) and simultaneous sodium thiosulfate intravenously (9 g/m2) for systemic neutralization of cisplatin. Concurrent (day 1) daily radiation therapy was delivered to the primary tumor and overt nodal disease to 66-74 Gy while the uninvolved lower neck received 50 Gy, at 2.0 Gy/fraction. RESULTS: Fifty-one (85%) patients completed the full RADPLAT protocol as planned. Fifty-seven of 60 patients were evaluable for response. Histological (n = 50) or clinical (n = 7) assessment of primary site revealed a complete response (CR) in 52 patients, partial response (PR) in 4, and stable disease (SD) in 1. Of the 40 patients presenting with nodal metastases, pathological (n = 31) or clinical (n = 6) assessment revealed a CR in 25, PR in 11, and SD in 1, while 3 were unevaluable. Overall, for both primary site and nodal disease, CR was attained in 44 (75%), PR in 12 (23%), and SD in 1 (2%) of the 57 evaluable patients. Only 2 (4%) of 57 evaluable patients have recurred above the clavicle, 1 in the primary site and 1 in the regional lymph nodes. Twelve patients (23%) have failed in distant sites. Grade III/VI toxicity has included gastrointestinal in 6, hematologic in 6, mucosal in 12, vascular in 4, and neurological in 4 patients. CONCLUSION: Concurrent radiation therapy and targeted supradose cisplatin (i.e., RADPLAT) can be safely delivered with high response rates and excellent loco-regional control in advanced Stage III/IV head and neck squamous cell carcinoma.

Adult↗
PubMed1997

Current and emerging treatments for pancreatic cancer.

The worldwide annual pancreatic cancer death rate equals its estimated annual incidence. Surgery has been considered the only curative modality for this disease, but only 5 to 15% of patients are candidates for potentially curative resection. Evidence that postoperative adjuvant treatment improves outcome has been limited to a single randomised trial of a well tolerated split-course chemoradiation regimen. More intensive regimens have since been developed and are associated with, at best, a modest improvement in patient outcome. The potentially significant morbidity associated with pancreaticoduodenectomy, which can compromise the delivery of postoperative adjuvant chemoradiation, has led to the development of preoperative adjuvant ('neoadjuvant') chemoradiation in these patients. Although experience suggests that such an approach is feasible, its ultimate impact awaits further evaluation. Combined modality therapy has produced the most promising results in patients with unresectable or locally advanced disease. However, only modest improvements in median survival and minimal increases in long term survival have so far been achieved. This observation has encouraged many investigators to devise innovative methods of delivering therapy, including radioisotope implantation and intraoperative radiation therapy (IORT). Combined modality therapy with radioisotope implantation appears to have the greatest potential for improving local control and survival in these patients. IORT may be associated with lower morbidity than radioisotope implantation, but its impact may be limited by the radiobiological disadvantage associated with single dose boost therapy. Although new radiosensitising drugs are being tested, the problem of distant metastasis remains significant. New chemotherapeutic agents such as gemcitabine appear to have the potential to produce better results than those achieved over the last 35 years with fluorouracil. Investigations into the optimal integration of different therapeutic modalities, along with continued advances in surgery, radiation and systemic therapy, should lead to the increased use of modern multimodality interventions. In turn, this will lead us towards further improvements in outcomes for patients with pancreatic carcinoma.

Antimetabolites, Antineoplastic↗
PubMed1996

Prognostic significance of tumor fixation of rectal carcinoma. Implications for adjunctive radiation therapy.

BACKGROUND: This study was conducted to assess the prognostic significance of adjunctive radiation in the surgical management of rectal carcinoma patients with tumor fixation. METHODS: Two hundred and ninety-seven patients with a histologic diagnosis of adenocarcinoma of the rectum were treated with high dose preoperative radiation ( > or = 45 Gray [Gy]) followed by surgical resection of the tumor (Group A). One hundred and seventy-four patients underwent initial curative surgery (Group B) followed by selective postoperative radiation (45-50 Gy) for those with pathologic T3, T4, or N+ (B2, C) cancers (N = 143). The two patient groups were compared by presenting clinical stage of the disease to assess the prognostic significance of tumor fixation on results of adjunctive therapy. Follow-up ranged from 24 months to 180 months. RESULTS: The 5-year actuarial survival of Groups A and B was similar, 69% and 61% respectively. Survival was significantly better for Group A patients with fixed cancer (57% vs. 33%, P = 0.003). Survival was also better for patients in Group A with tumors located in the distal rectum (70% vs. 56%, P = 0.02). The local recurrence rate for patients with tumors located in the distal rectum was 17% for Group A and 19% for Group B (P = 0.74). The local recurrence rate for fixed cancers was 23% and 50% for Group A and Group B respectively (P = 0.0009). The incidence of small bowel complications (Grade 3 or 4) was lower for patients undergoing preoperative radiation compared with patients treated with postoperative radiation, (4% vs. 13%, P < 0.05). CONCLUSIONS: When special considerations of sphincter-preserving surgery are not an issue, mobile rectal carcinoma may be effectively treated with surgery and selective postoperative radiation. However, fixed tumors, especially those located in the distal rectum, are better treated with high dose preoperative radiation.

Adenocarcinoma↗
PubMed1995

Thermal response and hyperthermic radiosensitization of scid mouse bone marrow CFU-C.

PURPOSE: Scid mice are severely immunodeficient as a result of a defective recombinase system. Mice with the scid mutation have been shown to have an increased sensitivity to ionizing radiation, presumably as a result of an inability to repair DNA damage. Little is known of the impact of this mutation on the thermal response and on hyperthermic radiosensitization. This investigation established the thermal response (42-44 degrees C), patterns of thermotolerance development, and the impact of hyperthermia (60 min at 40 degrees C or 42 degrees C) on the radiation response of bone marrow colony forming unit-culture cells (CFU-C) in scid mice. METHODS AND MATERIALS: Anesthetized scid mice (pentobarbital, 90 mg/kg) were killed by cervical dislocation and the nucleated marrow obtained from both tibia and femora by passing 2 ml of cold McCoy's 5A medium supplemented with 15% fetal bovine serum through each bone. Single cell suspensions of nucleated marrow were heated in 12 x 75 mm sterile tissue culture tubes at a concentration of approximately 5 x 10(6) cells/ml. Radiation, when used, was delivered immediately prior to hyperthermia by a 137Cs irradiator (dose rate of 1.20 Gy/min). Colony forming unit-culture were cultured in semisolid agar in the presence of colony stimulating factor (conditioned medium from L929 cells) for 7 days. RESULTS: The slope of the radiation dose-response curve for CFU-C in scid mice was biphasic, the Dos (+/- SE) were 0.29 +/- 0.03 Gy and 1.09 +/- 0.20 Gy, respectively. The Dos of the radiation dose-response curve for wild type marrow from CB-17 and Balb/c mice were 1.28 +/- 0.05 Gy and 1.47 +/- 0.15 Gy, respectively. The Dos of the hyperthermia dose-response curves for scid mice were 75 +/- 5, 10 +/- 1.4, and 4 +/- 0.2 min, respectively, for temperatures of 42 degrees, 43 degrees, and 44 degrees C. Thermotolerance development at 37 degrees C increased to a maximum at approximately 240 min after acute hyperthermia (15 min at 44 degrees C) and thereafter, decreased to control levels within 15 h. Thermotolerance did not develop in scid CFU-C during chronic hyperthermia at temperatures < 42.5 degrees C. Hyperthermia (60 min at 40 degrees or 42 degrees C) immediately after ionizing radiation did not significantly alter the terminal slope of the radiation dose-response curve of scid CFU-C (Do = 1.28 +/- 0.08 Gy). By contrast, hyperthermia following radiation of wild type CFU-C resulted in a decrease in the Do from 1.47 +/- 0.05 Gy (Balb/c, rad only) to 1.31 +/- 0.08 or 1.06 +/- 0.18 Gy for 60 min at 40 degrees or 42 degrees C, respectively. CONCLUSION: These results show that the thermal response and the pattern of thermotolerance development of scid CFU-C were similar to that of wild type Balb/c CFU-C, but that hyperthermia given immediately after ionizing radiation did not alter the radiation response of scid CFU-C. The scid mutation does not increase hyperthermic sensitivity or change the pattern of thermotolerance development of scid mouse CFU-C, implying that the scid mutation is not involved with thermal response, but does render the already radiation-sensitive scid cells incapable of thermal radiosensitization.

Animals↗
PubMed1995

A phase II trial evaluating selective use of altered radiation dose and fractionation in patients with unresectable rhabdomyosarcoma.

PURPOSE: Between 1987 and 1991, 25 children with advanced rhabdomyosarcoma (20 with IRS Group 3 disease and 5 with Group 4 disease) were entered on a prospective study evaluating selective use of hyperfractionated irradiation (HFI) and reduced-dose conventionally fractionated irradiation (CFI), based on disease status following induction chemotherapy (ifosfamide or melphalan, followed by vincristine, adriamycin, and cyclophosphamide combination) with or without delayed surgery. METHODS AND MATERIALS: Patients with gross disease following induction chemotherapy with or without delayed surgery, and whose primary tumor sites did not involve the central nervous system, received HFI (n = 12) at 1.1 Gy twice-a-day to 59.4-63.8 Gy total. Patients with parameningeal primaries and intracranial disease extension received HFI with initiation of therapy (n = 2). Those with microscopic disease following induction chemotherapy with or without delayed surgery (n = 11) received reduced-dose CFI to 40 Gy. Active follow-up ranges from 28-75 months (median = 43 months) with no patient lost to follow-up. RESULTS: Eighteen patients (72%) are alive and without evidence of disease, including 8 of the children with gross residual disease postinduction therapy. The absolute 2-year continuous local tumor control rate is 86% for all patients. Among the 14 who received HFI, the absolute 2-year continuous local tumor control rate is 75% at 33 to 67 months (median = 38 months) postirradiation. Hyperfractionated irradiation was associated with expected enhancement of acute reactions, which all resolved with conservative medical management. Grade 4 or 5 acute toxicities were not seen. Significant late radiation morbidity has, thus far, been minimal and limited to Grade 1 and 2 events. Among the 11 who received reduced-dose CFI, the absolute 2-year continuous local tumor control rate is 100% at 25 to 70 months (median = 40 months) postirradiation. CONCLUSION: This limited experience suggests that HFI to a dose level of 60 Gy can be used selectively in children with advanced rhabdomyosarcoma left with gross disease following induction chemotherapy, with or without delayed surgery, with an apparent improvement in local control, and minimization of potential late radiation toxicity. Concurrently, those left with microscopic disease following induction therapy can be selectively treated with reduced-dose CFI with excellent local control.

Adolescent↗
PubMed1995

Local tumor control in rhabdomyosarcoma following low-dose irradiation: comparison of group II and select group III patients.

PURPOSE: To determine whether low-dose irradiation (i.e., approximately 40 Gy at 1.5-1.8 Gy/fraction), which is associated with > or = 90% local control in children with initially resected rhabdomyosarcoma and microscopic residual [Intergroup Rhabdomyosarcoma (IRS) group II disease], achieves comparable results in children with locally advanced rhabdomyosarcoma (IRS group III) left with microscopic disease after induction chemotherapy with or without delayed surgery. METHODS AND MATERIALS: Among 103 patients entered on five successive studies between 1968 and 1991, 24 had evidence of microscopic residual disease after initial surgical resection (IRS group II) and received low-dose irradiation. Initial chemotherapy was used in 79 with IRS group III disease. In 28 of these 79 group III patients, chemotherapy alone (n = 16) or in combination with delayed surgery (n = 12) reduced disease to microscopic levels prior to the start of radiotherapy based upon which they received low-dose irradiation. All have a minimum 2-year follow-up and median age of 4 years. Primary tumor sites among the 24 with group II disease included: orbit (5), parameningeal (2), nonparameningeal head and neck (3), genitourinary: nonbladder/prostate (5), extremity (4), and other (5). Irradiation dose ranged from 32-50 Gy, with a median and modal dose of 40 Gy. Primary tumor sites among the 28 with group III disease selectively treated with low-dose irradiation included: orbit (1), parameningeal (6), nonparameningeal head and neck (4), genitourinary: bladder/prostate (12) and nonbladder/prostate (1), extremity (1), and other (3). Irradiation dose ranged from 33-52 Gy, with a median and modal dose of 40 Gy. RESULTS: Local disease control has been maintained in 23 of 24 patients (96%) with group II disease. Local control occurred in eight of nine (89%) group II patients receiving < 40 Gy and in all 15 receiving > or = 40 Gy (p = 0.26). Twenty (83%) are alive and free of disease. Twenty-two of the 28 patients (79%) with group III disease treated with low-dose irradiation have maintained continuous local control of disease which was not statistically different from the group II patients (p = 0.08). Local control occurred in 7 of 11 (64%) group III patients receiving < 40 Gy vs. 15 of 17 (88%) receiving > or = 40 Gy (p < = 0.14). Nineteen (68%) are alive and free of disease. Survival in these group III patients is significantly worse than that of the group II patients, with 19 (68%) alive and free of disease (p = 0.04). CONCLUSION: Children with locally advanced rhabdomyosarcoma (IRS group III) who have only microscopic disease after induction chemotherapy with or without delayed surgery have a high likelihood of achieving local control with low-dose irradiation. For this group, data suggest treatment to a dose level of at least 40 Gy.

Adolescent↗
PubMed1995

A prospective neurocognitive evaluation of children treated with additional chemotherapy and craniospinal irradiation following isolated central nervous system relapse in acute lymphoblastic leukemia.

PURPOSE: A prospective assessment of neurocognitive performance was conducted in children with acute lymphoblastic leukemia (ALL) following isolated central nervous system (CNS) relapse to evaluate the impact of additional systemic/intrathecal (IT) chemotherapy and craniospinal irradiation (CSI) upon long-term intellectual function. METHODS AND MATERIALS: Twenty-one children with ALL manifesting an isolated CNS relapse between 1984 through 1989 underwent serial evaluations of intellectual function. Neurocognitive function was measured by the full-scale intelligence quotient (FSIQ) as determined by the age-appropriate Wechsler Intelligence Scale and by achievement in reading, math, and spelling as assessed by the Wide Range Achievement Test (WRAT). Intelligence testing was initiated following isolated CNS relapse after clearance of cerebrospinal fluid (CSF) cytology but prior to CSI and continued at annual intervals for a minimum of 4 years postmeningeal failure. Protocol treatment for isolated CNS relapse consisted of reinduction and maintenance systemic therapy, intrathecal (IT) triple-agent chemotherapy, and early CSI (cranium to 24 Gy and spine to 15 Gy at 1.5 Gy/fraction) as outlined on the institutional "Total XI" trial. RESULTS: All 21 children attained secondary CNS remission and underwent the planned additional systemic/IT chemotherapy and CSI. Fourteen of the 21 children remain in secondary continuous remission, while the remaining 7 experienced a second relapse and were removed from further neurocognitive assessment. For the eight female and six male long-term survivors, mean ages at original diagnosis and at CSI were 5.7 years (range = 0.6-16.2) and 7.0 years (range = 1.8-17.0), respectively. At a median follow-up interval of 4.6 years (ranges 1.7-6.8) post-CNS relapse, comparison of group mean initial to final FSIQs revealed no statistically significant difference between the two measures (94.5 vs. 95.9, respectively, n = 11, p = 0.52). None of the children are functioning in the mentally retarded range. Final FSIQ outcome directly correlated with initial FSIQ (p = 0.00005, n = 11), age at diagnosis (p = 0.009, n = 14), and age at CSI (p = 0.011, n = 14). In addition, change between initial and final FSIQ scores inversely correlated with age at diagnosis (p = 0.009) and age at CSI (p = 0.018) but not with baseline IQ score (p = 0.41). Initial FSIQ scores were not influenced by either age at diagnosis (p = 0.12) or age at CSI (p = 0.14). Final group mean (range) WRAT scores in reading, math, and spelling were measured to be 94.7 (68-132), 95.6 (69-126), and 93.7 (77-122), respectively (n = 13). Final reading and math scores directly correlated with both age at diagnosis (p = 0.01) and age at CSI (p = 0.009). Spelling outcome did not correlate with either age at diagnosis (p = 0.25) or age at CSI (p = 0.24). Nine children are placed in regular classrooms, while the remaining five require a mixed classroom environment. CONCLUSION: In our study, children with ALL experiencing an isolated CNS relapse tolerated additional systemic/IT chemotherapy and CSI without apparent deterioration of group serial intellectual scores. However, longitudinal analyses of group intellectual measures obscured the independent impact of initial FSIQ, age at original diagnosis, and age at CSI upon individual neurocognitive outcome. Early and more intensive psychoeducational stimulation may be needed in very young children presenting with low initial FSIQ scores who are treated with CSI and additional chemotherapy following isolated CNS relapse in ALL.

Adolescent↗
PubMed1995

Combined intraoperative radiation and perioperative chemotherapy for unresectable cancers of the pancreas.

PURPOSE: To evaluate the effectiveness of combined intraoperative radiation therapy (IORT) and perioperative chemotherapy in the management of unresectable pancreatic cancer. MATERIALS AND METHODS: Forty-nine patients with localized unresectable adenocarcinoma of the pancreas were treated in a multimodality program of initial IORT and perioperative chemotherapy (fluorouracil [5-FU]/leucovorin) followed by combined external-beam radiation (40 to 55 Gy) and continued chemotherapy. Patients were evaluated for toxicity, pattern of failure, and survival. The follow-up times of these patients range from a minimum of 12 months to a maximum of 62 months, with a median of 28 months. RESULTS: The incidence of perioperative mortality was 0%. Early postsurgical morbidity (grade 3/4) was observed in seven of 49 patients (14%) and late treatment-related morbidity (grade 3/4) in eight of 43 patients (19%) alive beyond 6 months. Morbidity was primarily gastrointestinal (GI), with no hematologic toxicities observed. The median survival time in the total group of patients is 16 months, with a 2-year survival rate of 22% and a 4-year survival rate of 7%. Freedom from local progression of disease was achieved in 71% of patients. CONCLUSION: The patients who undergo IORT with electrons and treated with perioperative chemotherapy (5-FU leucovorin) followed by additional external-beam radiation and chemotherapy appear to have improved survival, with few early or late complications. Dose escalation of external-beam radiation and chemotherapy may further improve local control of disease and survival of patients.

Actuarial Analysis↗