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Biomedical subjects

B Hilaris

Publications and source records attributed to B Hilaris.

At least 19 recordsLinked to original sources

Role of brachytherapy in malignant melanoma: a preliminary report.

From August 1979 to May 1986, various brachytherapy techniques were applied at Memorial Sloan Kettering Cancer Center (MSKCC) in an adjuvant setting with/without surgery and external radiation therapy in the management of advanced malignant melanoma. Thirty-three patients underwent brachytherapy procedures. The patients' ages ranged from 35 to 82 years, with a median age of 56 years. Fourteen patients had disease localized to the implant site, whereas 19 patients also had disseminated disease elsewhere. The indications for implant were residual gross disease (21), microscopically positive margins (3), and histologically negative but clinically close margins of resection (9). Local control at the implant site was noted in 80% of patients at 6 months and 42% of patients at 1 year; two patients had reached 54 months and 72 months with no evidence of disease. Local control was 100% (9/9) in patients with histologically negative but clinically close margins of resection, and 48% (11/23) with microscopically positive margins and/or gross residual disease. Complications were seen as follows: delay in wound healing (1), wound infections (4), radiation enteritis (1), small bowel obstruction (1). The present study suggests that brachytherapy combined with surgery can achieve a good local control in patients with negative but clinically close margins of resection. In patients with gross residual disease who are at a high risk for local recurrence, approximately one-half can be locally controlled with this approach. These preliminary results should be tested in a prospective controlled study.

Adult

Preoperative therapy for esophageal cancer: a randomized comparison of chemotherapy versus radiation therapy.

Ninety-six patients with operable epidermoid cancer of the esophagus were entered into a phase III, random assignment study designed to compare the efficacy of two preoperative approaches (chemotherapy [CT] or radiation therapy [RT]). Major study end points were objective response rates, surgical outcome, and recurrence pattern. Patients were randomly assigned to receive either two cycles of cisplatin, vindesine, and bleomycin or 55 Gy of radiation before a planned surgical procedure. Postoperative crossover therapy (radiation to those receiving preoperative CT and vice versa) was given to patients with T3Nany or unresectable tumors. Objective response rates of the primary tumor to preoperative therapy were similar (RT 64%, CT 55%), as were operability rates (RT 77%, CT 75%), resection rates (RT 65%, CT 58%), and operative mortality (RT 13.5%, CT 11.1%). Significantly higher doses of CT could be administered when CT was given as initial therapy, rather than after RT/surgery. Local failure or persistence occurred in 33% of operable patients. The median survival for all patients was 11 months; 20% remain alive without disease (median follow-up, 34 months). Because of the crossover design, it was not possible to analyze survival according to the preoperative therapy arm alone. This study suggests that since CT is as effective in treating local tumor as RT, but can also potentially treat systemic disease, investigational programs using CT before surgery as part of initial treatment for localized esophageal cancer should continue. However, if a significant impact on overall survival is to be achieved, more effective chemotherapy regimens or schedules need to be identified. Outside of carefully designed clinical trials, surgery alone or radiation alone remain standard therapy.

Analysis of Variance

Treatment of primary unresectable carcinoma of the pancreas with I-125 implantation.

Between January 1 1974 and October 31 1987, 98 patients with biopsy proven unresectable adenocarcinoma of the pancreas were treated with I-125 implants during laparotomy. Presenting symptoms were pain (57 patients), jaundice (45 patients), and weight loss (34 patients). All patients underwent laparotomy and surgical staging. Thirty patients had T1NoMo disease, 47 patients had T2-3NoMo disease, and 21 patients had significant regional lymph node involvement (T1-3N1Mo). The surgical procedure performed was biopsy only (16 patients), gastric bypass (36 patients), biliary bypass (49 patients), and partial or total pancreatectomy with incomplete resection (5 patients). The total activity and the number of seeds used were determined from the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. Stereoshift localization X ray films were taken 3-6 days after operation. The mean activity, minimal peripheral dose (MPD), and volume of the implants were 35 mCi, 13,660 cGy, and 53 cm3, respectively. In addition, 27 patients received postoperative external irradiation and 27 patients received chemotherapy. Postoperative complications were observed in 19 patients. These included post-operative death (1 patient), biliary fistula (4), intraabdominal abscess (4), GI bleeding (3), gastric or small bowel obstruction (6), sepsis (5), and deep vein thrombophlebitis (4). Pain relief was obtained in 37/57 patients (65%) presenting with pain. A multivariate analysis showed that four factors significantly affected survival: T stage, N stage, administration of chemotherapy, and more than 30% reduction in the size of the implant on follow-up films. The median survival for the entire group was 7 months. A subgroup of patients with T1No stage disease who received chemotherapy survived 18.5 months. The indications for I-125 seed implantation in unresectable carcinoma of the pancreas are discussed.

Adenocarcinoma

Brachytherapy.

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Antineoplastic Agents

Local recurrence in adult soft-tissue sarcoma. A randomized trial of brachytherapy.

We conducted a prospective randomized study of the benefit of adjuvant radiation therapy delivered by the brachytherapy technique in 117 adult patients who had soft-tissue sarcoma that was on an extremity or superficially localized to the trunk. A significant decrease in local recurrence was demonstrated in the patients receiving brachytherapy. The benefit did not appear to be due to any maldistribution in the known prognostic factors of size, site, depth, presentation with recurrence, or histologic grade. The decrease in local recurrence appears to be due to the decreased local recurrence in high-grade sarcomas. Survival differences were not identified, and accrual and follow-up were continued.

Adult

The treatment of single brain metastasis from non-oat cell lung carcinoma. Surgery and radiation versus radiation therapy alone.

Between 1978-1980, 104 patients with single brain metastases (SBM) from non-small cell lung carcinoma (NSCLC) were treated at Memorial Sloan-Kettering Cancer Center (MSKCC). These included 35 patients treated with surgical resection and radiation (S + ERT) and 69 patients treated with conventional external beam radiation therapy alone (ERT). Surgical resection was combined with whole brain (WBRT) and focal radiation in 83% and 17% of patients, respectively. In the ERT group, all patients received WBRT. Both treatment groups were similar with regard to age, sex, stage distribution, location and size of SBM, and time to relapse from initial diagnosis of NSCLC. The histologic examination, however, revealed adenocarcinoma predominating in those patients receiving S + ERT and epidermoid carcinoma in those receiving ERT. Follow-up treatment, symptomatic, and CTT response rates were evaluated. With S + ERT, the overall subjective and objective responses were 80% and 87%, respectively, and with ERT, 83% and 72% (of the 47 patients available for follow-up CT scans), respectively. Survival data indicate a significant advantage of S + ERT over ERT with a median survival of 16 months versus 4 months (P less than 0.0001). Three major factors, however, may have contributed to this difference: (1) patients in the S + ERT group generally received more aggressive initial treatment to the primary disease in the lung (72%) compared to the ERT group (36%); (2) in the S + ERT group, extracranial disease was absent at the time of SBM diagnosis in 49% of the S + ERT group compared to 26% in the ERT group; and (3) distant metastases were present in only 6% of the surgical patients yet, they were present in 49% of those treated with radiation alone. In one subset of patients, however--those with a radically treated primary and no extracranial disease--S + ERT resulted in a median survival of 33 months with 33% of the population still alive with no evidence of disease compared to 12 months and 0%, respectively, with ERT alone. Moreover, intracranial relapse was the cause of death in only one S + ERT patient (9%), yet it accounted for 50% of the ERT deaths. These data suggest that an aggressive approach to SBM in such favorable prognostic patients may indeed improve survival.

Adenocarcinoma

Neoadjuvant chemotherapy and surgery of cancer of the esophagus.

Neoadjuvant, or preoperative, chemotherapy for esophageal cancer has become an area of increasing interest because of the failure of conventional therapy (surgery or radiation) to improve disease-free or overall survival. Several autopsy series have demonstrated that, in many symptomatic western patients, esophageal cancer is a systemic disease. Neoadjuvant chemotherapy thus, in theory, allows a simultaneous attack on both the primary and metastatic disease. A number of single-arm, phase II multimodality trials have been completed. Toxicities of chemotherapy, while substantial, have been tolerable. With careful attention to detail, operative morbidity and mortality has not been increased. Large-scale randomized trials are needed to evaluate the impact of this technique on disease-free and overall survival.

Antineoplastic Combined Chemotherapy Protocols

A non-looping afterloading technique for base of tongue implants: results in the first 20 patients.

The results of treatment in the first 20 patients treated by a non-looping afterloading technique for base of tongue implant are described. Ten patients had carcinoma recurrent in the base of tongue after previous treatment and they were treated by implant alone. The other 10 patients had previously untreated carcinoma of the base of tongue and they were treated with a combination of interstitial implant, external radiation therapy and surgery. The minimum follow-up is 1 year and maximum 5 years. No local or regional failures have occurred in the previously untreated patients. No local failures have occurred in the previously treated patients who had lesions up to 4 cm in diameter, but three out of four patients with recurrent lesions larger than 4 cm have failed locally. Two patients developed necrosis related to the implant; the factors responsible for this are discussed.

Adenocarcinoma

Recurrent stage I endometrial carcinoma: results of treatment and prognostic factors.

Recurrences of clinical Stage I endometrial carcinoma after initial treatment are rare. They are nonetheless a serious complication, uniformly associated with poor survival outcome. Between 1969-1980, 20 patients with clinical Stage I endometrial carcinoma were treated for recurrent tumor at the time of first relapse. Nonpapillary adenocarcinoma represented 70% of the primary tumors (pure adenocarcinoma, 50%; adenosquamous, 15%, clear cell, 5%) and papillary adenocarcinoma, 30%. The most common presenting symptom was vaginal bleeding, occurring in 95% of patients. The median time to recurrence after completion of primary treatment was 9.5 mo: Adenocarcinoma relapsed at a median time of 33 mo, adenosquamous, 6 mo and papillary adenocarcinoma, 4 mo. The vagina was the site of relapse in 65% of patients, the abdomen in 20%, the pelvis in 10% and the lung in 5%. Ninety-five percent of recurrences were treated with curative intent. Complications were seen in three patients, small bowel obstruction (2 pts) and vaginal vault necrosis (1 pt); however, these patients responded effectively to conservative treatment. Minimum follow-up of 4 years was available in 18 pts (90%). Actuarial 4 yr overall and NED survival was 50%, respectively, with a median survival of 39 mo to date. There have been no deaths from further recurrence of endometrial cancer beyond 39 mo. Significant prognostic factors for 4 year survival were 1) recurrence site--vagina, 82% (9/11 pts) vs extravagina, 0% (0/7 pts; median survival: 8 mo) [p = .0001]; and 2) histologic cell type--non-papillary carcinoma, 75% (9/12 pts) vs papillary adenocarcinoma, 0% (0/6 pts; median survival: 8 mo) [p = .002]. Our review suggests that: (1) Histology and site of relapse are important prognosticators of treatment outcome; (2) Long term survival may be achieved in vaginal recurrences with aggressive local treatment; and (3) There may be a role for multimodality ovarian type treatment in overall management of recurrent papillary adenocarcinoma, a cell type that appears to exhibit a tendency towards extrapelvic spread refractory to definitive loco-regional treatment.

Adenocarcinoma

The effects of permanent I-125 interstitial implantation on cortical bone.

From 1973 to 1980, 1,427 cancer patients were treated by the Brachytherapy Service, Radiation Oncology Department of Memorial Sloan-Kettering Cancer Center (MSKCC) with I-125 permanent interstitial implantation. Concern has been expressed with regard to the possible toxic effects of the low average photon energy (28 kev) of I-125 on bone, secondary to its increased absorption in these tissues because of the photoelectric effect. In an attempt to address this concern with respect to cortical bone, we reviewed pertinent data on those patients whose site of implant was at close proximity to osseous tissue in the pelvic, chest wall and head and neck regions. The review included 74 sites in 58 patients having no prior history or clinical evidence of any pathologic or metabolic bony disorder. Long term (greater than 1 year) follow-up was available in over 50% of the cases, with 10 patients followed more than 4 years. Local control rate for the 74 implanted sites was 93%. The implanted activity ranged from 1.6 to 48.8 mCi and the implanted volume from 0.5 to 152 cm3. At this follow-up range, there appears to be no excessive osseous toxicity either clinically or radiologically with I-125 permanent implantation.

Adult

Postoperative vaginal radiation in endometrial cancer using a remote afterloading technique.

Carcinoma of the endometrium is the most common malignancy of the female genital tract. In early stage endometrial cancer, surgery remains the primary mode of treatment while radiation therapy plays an adjuvant role. Prophylactic vaginal radiation has been shown to reduce significantly the incidence of vaginal recurrences. Between the years 1969-1976, 330 patients with FIGO Stages I and II endometrial cancer were treated according to a standard departmental policy in which 40 Gy of external radiation was given to high risk Stage I and all Stage II patients in combination with surgery and intravaginal radiation. Stage I was considered high risk if the tumor was of high grade or exhibited deep myometrial invasion. Vault radiation was delivered with a remote afterloading technique to a point .5 cm from the surface of the applicator; a total dose of 21 Gy was delivered in three fractions spaced two weeks apart over four elapsed weeks. With this regimen, the mucosal surface received a total equivalent dose of 40 Gy. These treatments were given on an outpatient basis without the need for any sedation or analgesics. All patients, regardless of stage, grade, or depth of myometrial invasion received adjuvant post-operative vaginal radiation. The minimum follow-up was 5 years, with a median follow-up of 8.5 years. The overall pelvic and/or vaginal recurrence rate was 2.7%. The incidence of vaginal complications was 3.7%. It appears that the remote afterloading treatment (RAT) for vaginal radiation is a very cost-effective therapeutic alternative, which produces minimal early or late complications and gives complete protection from radiation exposure to the medical staff. The advantages of a remote afterloading technique in delivering vaginal vault radiation in endometrial cancer are discussed in this paper.

Brachytherapy

Interstitial radiation: short-term palliation or curative therapy?

The management of clinically localized prostatic cancer by interstitial implantation of 125I seeds has been under exploration at Memorial Sloan-Kettering Cancer Center for thirteen years. This investigation was prompted by clinical evidence of the radioresponsiveness of some prostatic cancers, the limited applicability of surgical excision, and the possibility that interstitial therapy would have less of an adverse effect on the quality of life than would alternative treatments. Cumulative experience indicates that the technique is associated with low morbidity and mortality and high functional preservation rates; local control rates (routine biopsies were not done), within the constraints of still-limited follow-up intervals, are in the 80 per cent to 90 per cent range; and actuarial survival rates at nine years (including patients who received endocrine therapy for metastatic or intractable local disease) are approximately 90 per cent for T1, 60 per cent for T2, and 45 per cent for T3 lesions. Approximate actuarial nine-year survival rates are 80 per cent for all patients with negative nodes and 50 per cent for all patients with positive nodes. Taking into account limitations of the data and the hazards of comparing this therapy with other uncontrolled treatments, 125I appears to be a therapeutic option for the control of clinically localized prostatic cancer.

Actuarial Analysis

Pleural mesothelioma.

Seventy-six patients with pleural mesothelioma were seen at Memorial Hospital from 1939 to 1972. There were 10 with benign and 66 with malignant mesotheliomas. The latter were histologically divided into 39 epithelial and 27 fibrosarcomatous types. Main symptoms were chest pain, dyspnea, and cough. Most of the patients with malignant disease had clinical and radiologic evidence of effusion with or without an intrathoracic mass. Thirty-seven patients had primary untreated mesothelioma and 29 patients had disease that had previously been treated elsewhere. Treatment at Memorial Hospital consisted of surgery, with or without radiation therapy, and supplemental chemotherapy. Survival was related to extent of disease and to treatment. In patients with epithelial mesothelioma confined to the hemithorax, resection was associated with a median survival of 21 months. When irradiation was the primary treatment, the median survival was 8 months. In fibrosarcomatous mesotherlioma, the median survival with resection was 11 months and with radiation, 9 months. Median survival in patients with advanced or recurrent disease was 3 to 6 months. It is concluded that epithelial mesotherlioma with diffused pleural involvement continues to carry a grave prognosis. Better survival is obtained where pleurectomy with resection of the bulk of the tumor is combined with external irradiation and systemic chemotherapy. In fibrosarcomatous mesothelioma, complete resection offers a significant chance of long-term survival. In patients with benign mesothelioma, none had recurrence nor died of disease after adequate resection.

Adolescent

The influence of dose fractionation on acute and late reactions in patients with postoperative rasiotherapy for carcinoma of the breast.

The clinical courses of 418 patients with breast carcinoma who received postradical-mastectomy radiation therapy to the internal mammary and supraclavicular are were revied in order to determine the normal tissue tolerance with various time-dose fractionation radiation regimens. Four different dose fractionation schedules wereemplyed during the period 1958-1968 at Memorial Hospital: 4900 rads/10f/32d; 4410 rads/9f/30d; 5000 rads/13f/18d; and 4600 rads/20f/28d. There was no difference in the acute reaction or local recurrence rate of the tumor in the irradiated area among the four fractionation schemes, but the late effects were quite different. Patients who received 4900 rads in 10 fractions in 32 days had a 33% incidence of subcutaneous fibrosis.A similiar dose in 13 fractions in 21/2-3 weeks resulted in about 17% subcutaneous fibrosis. No significance of these clinical findings is discussed in relation to the various formulae currently being used to express time-dose equivalence.

Breast Neoplasms

Iodine 125 source in interstitial tumor therapy. Clinical and biological considerations.

Our clinical experience with interstitial tumor therapy is presented in 2 groups of patients: 98 patients with metastatic carcinoma in neck lymph nodes implanted with iodine 125, iridium 192 or radon 222 encapsulated sources, and 105 patients with primary unresectable lung tumors, which were implanted either with radon 222 or iodine 125 seeds. The local tumor control rates with iodine 125, radon 222 and iridium 192 were 78 per cent (38/49), 65 per cent (15/23) and 58 per cent (7/12), while the local complication rates were 17 per cent, 35 per cent and 43 per cent, respectively. An analysis of the tumor control rate as a function of the implanted tumor dose shows that the iodine 125 implants with a delivery of the minimal effective tumor dose of 16,000 rads have a higher therapeutic effect than either radon 222 or iridium 192. The results of the patients with unresectable lung tumors similarly show that the implants with iodine 125 sources are superior to those with radon 222. The advantages could stem from the better spatial dose distribution, and from radiobiologic considerations associated with low dose rates, continous irradiation, and possibly gains in RBE. There present clinical data clearly demonstrate that iodine 125 seeds have a higher therapeutic ratio than radon 222 seeds. There are, in addition, distinct physical advantages making iodine 125 an attractive substitute for radon 222 for the interstitial implantation of malignant tumors.

Head and Neck Neoplasms