The combined neurosurgical-thoracic management of superior sulcus tumors.

Thirty patients with superior sulcus carcinoma were prospectively evaluated over an 18-month period. All patients underwent complete neuroradiological evaluation by computed tomography (CT) and myelography. Prior to operation, brachial plexopathy was noted in 20 patients (67%), and invasion of the spine in eight (27%). Using a team approach, gross total resection of tumor was achieved in 17 of 26 patients (65%) undergoing thoracotomy. There was no operative mortality. The use of a team approach allows extended surgical resection, especially when the spine is involved. In patients presenting with brachial plexopathy or cord compression, de novo surgery before radiation may provide better long-term palliation and pain relief.

Wound complications in the multimodality treatment of extremity and superficial truncal sarcomas.

The incidence and severity of wound complications were examined in 105 patients with extremity and superficial truncal sarcomas who were eligible for wide local excision with or without adjuvant perioperative brachytherapy (BRT) and/or chemotherapy. Fifty-four cases from the eligible group were entered into a randomized prospective trial of the efficacy of BRT in decreasing local recurrence. In the eligible patients, major wound complications occurred in nine of 41 (22%) of the BRT cases, compared with two of 64 (3%) of the non-BRT patients, which was a significant increase (P = .002). The combined frequency of major and moderate wound complications was also significantly increased in the BRT (18 of 41, 44%) compared with the non-BRT (nine of 64, 14%) patients (P = .0006). The median duration to complete resolution of these complications was 189 days (14 to 597) in the BRT, compared with 49 (11 to 170) days in the non-BRT group (P = .0005); however, no amputations were required, and only 14% of the BRT-associated wound complications were of prolonged duration, ie, greater than 200 days. In the randomized study, both the total number of complications, and the combination of major and moderate complications were increased significantly in the BRT v the non-BRT patients. Adjuvant Adriamycin (Adria Laboratories, Columbus, OH) administered in 60 mg/m2 increments to a cumulative dose of 540 mg/m2 did not appear to impair wound healing even when administered within 15 days of operation. Significant wound complications occur in major resections of extremity and superficial truncal sarcomas. If the addition of adjuvant BRT produces a decrease in local recurrence, then either patient selection will have to be more rigidly applied, especially in wounds where skin flap blood supply is tenuous, or the technique will need to be modified to balance the short-term aim of reducing wound complications with the long-term goal of local tumor control.

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.

Combination cyclophosphamide, Adriamycin, and vincristine rapidly alternating with combination cisplatin and VP-16 in treatment of small cell lung cancer.

Forty-four patients with small cell lung cancer were treated with an intensive chemotherapy induction program consisting of combination cyclophosphamide, Adriamycin, and vincristine rapidly alternating with combination cisplatin and VP-16 followed by prophylactic cranial radiotherapy. After chemotherapy induction and cranial radiotherapy, patients with limited disease received multiple-field radiotherapy consolidation to the primary tumor site and mediastinum using thoracic computed tomographic scanning for field planning, and patients with extensive disease received chemotherapy maintenance. Patients with limited disease in complete remission following radiotherapy consolidation received no further treatment unless disease recurred. It was found that cyclophosphamide, Adriamycin, and vincristine could be alternated with cisplatin plus VP-16 at two-week intervals in 80 percent of patients on an outpatient basis and that two thirds of patients achieved clinical complete remission after two courses of each regimen. Locoregional radiotherapy delivered via multiple fields was effective in increasing the complete remission rate in patients with limited disease and was well tolerated. The median survival time was 18.5 months in 24 patients with limited disease and 12.2 months in 20 patients with extensive disease. Four patients with limited disease who received chemotherapy induction and radiotherapy consolidation without maintenance chemotherapy and one patient with extensive disease remain alive and disease-free at more than five years.

Cisplatin, vindesine, and bleomycin chemotherapy of local-regional and advanced esophageal carcinoma.

Seventy-one patients with epidermoid carcinoma of the esophagus were treated with a three-drug combination of cisplatin, vindesine, and bleomycin. Forty-five patients had local-regional tumor and received chemotherapy prior to surgery or radiation therapy. Twenty-six patients with extensive disease were treated primarily with chemotherapy alone. The overall major objective response rate to cisplatin-vindesine-bleomycin was 53 percent (36 of 68 evaluable patients). Patients with local-regional disease had a higher response rate than those with extensive disease (63 and 33 percent, respectively). Following preoperative chemotherapy, 34 patients with local-regional disease underwent exploration. Resectable disease was present in 82 percent. There was no increase in operative morbidity or mortality (5.6 percent), when compared with historical control groups. The median survival for the preoperative chemotherapy group was 16.2 months, which is superior to that of a historical control group (p = 0.023). For patients with extensive disease, treated primarily with chemotherapy alone, the median duration of response was seven months. Toxicities of cisplatin-vindesine-bleomycin were in general well-tolerated, and included nausea and vomiting (seen less frequently because of extensive use of metoclopramide), alopecia, nephrotoxicity, and peripheral neuropathy. The dose-limiting toxicity was myelosuppression. Although conventional chemotherapeutic agents have little activity, these results indicate that the investigational combination of cisplatin, vindesine, and bleomycin can induce major regressions in a substantial proportion of patients with esophageal cancer. When this drug combination is used preoperatively, high resection rates and possibly improved survival are seen.

Transnasal permanent interstitial implantation for carcinoma of the nasopharynx.

A technique for transnasal permanent interstitial implantation of the nasopharynx with 125I seeds is described. This technique allows the precise placement of radioactive sources into mucosal and submucosal tumors, without the need for palatal fenestration. Preliminary results in 10 patients treated by this technique for recurrent nasopharyngeal carcinoma are presented. In the future we also hope to employ this technique for delivering "boost" irradiation to the primary site, in the initial definitive management of carcinoma of the nasopharynx.

The current state of intraoperative interstitial brachytherapy in lung cancer.

Low dose-rate intraoperative brachytherapy allows for a more precise tumor localization of the delivered radiation and its easier adaptation to the tumor shape than it is possible with external radiation. As a result a higher dose is usually delivered to the tumor volume and the damage to the normal lung is less. In an attempt to determine the value of lung brachytherapy we provide in this article a complete review of the evolution of brachytherapy in lung cancer at Memorial Sloan-Kettering Cancer Center, an experience which exceeds 1,000 patients. The use of encapsulated sources of I-125, greatly reduced radiation outside the treatment volume and simplified medical and nursing staff radiation protection. Lung brachytherapy in combination with surgery and postoperative external radiation, improved local tumor control in advanced tumors (from 63% to 76%) with no increase in late pulmonary morbidity, but only a modest survival advantage. The results of brachytherapy in patients with early lung cancer who had limited pulmonary reserve, suggest that intraoperative brachytherapy is an effective alternative treatment option. The limited experience with interstitial brachytherapy under fluoroscopic and CT guidance is encouraging, but needs more investigation.

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.

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.

The role of paraaortic node irradiation in the treatment of cancer of the cervix.

One hundred and twenty-seven patients with previously untreated carcinoma of the uterine cervix underwent pretreatment laparotomy between 1971 and 1980. Thirty-one were found to have paraaortic metastasis. Twenty-seven patients received paraaortic node external supervoltage radiation to the entire paraaortic chain, 4400 cGy, over 4 1/2 weeks, with 600-800 cGy, boost over 1 week, limited to the area of metastasis as marked at laparotomy. Twenty-nine percent (8/27) of the patients with paraaortic node metastases who were irradiated have survived 5 years or more. These patients have FIGO stages IB, IIA, or IIB; all have epidermoid carcinoma. Three of five patients (60%) with microscopic metastasis and five of twenty-two patients (23%) with gross metastasis in the paraaortic lymph nodes are long-term survivors. None of our long-term survivors have suffered late complications. There have been no fatalities from treatment related complications. We present a radiation technique for paraaortic radiation in these patients, and discuss the indications for paraaortic node radiation in cancer of the cervix.

Value of perioperative brachytherapy in the management of non-oat cell carcinoma of the lung.

Nearly one-half of all patients with non-oat cell carcinoma of the lung are found to have mediastinal lymph node metastases at the time of initial presentation. There is no consensus today on what constitutes best treatment in patients whose disease is confined to the chest and in whom mediastinal lymph node metastases are the only evident site of tumor spread. The overall survival of these patients is so low that the majority have been either excluded from therapy or have been treated palliatively by external radiation therapy. In an attempt to improve the control of mediastinal lymph node metastases in the operable patients, we began a pilot study in 1977 at Memorial Hospital to determine the value of perioperative brachytherapy (permanent Iodine-125 implantation of primary lung and a temporary Iridium-192 implantation of the mediastinum) with or without resection followed by a moderate dose of postoperative external beam irradiation. Eighty-eight patients with disease limited to one hemithorax (N2 MO) were treated with this combined method during the period 1977 through 1980. Locoregional control was observed in 76% of the 88 patients. The median survival is 26 months and the 2 year actuarial survival is 51%. There was no post-operative mortality. This pilot study has demonstrated that the combination of surgery, perioperative brachytherapy and external beam irradiation in non-oat cell carcinoma of the lung, metastatic to mediastinal lymph nodes, can improve the locoregional control and prolong survival with minimal early or late morbidity.

Radiation therapy of primary vaginal carcinoma.

Primary carcinoma of the vagina is rare, constituting only 1 to 2% of all neoplasms arising in the female genital tract. From 1950-1974, 36 patients with carcinoma of the vagina were treated with radiation at Memorial Sloan-Kettering Cancer Center (MSKCC); 35 (96%) had epidermoid carcinoma and one patient (4%) had adenocarcinoma. These patients were staged according to FIGO. Fourteen patients (39%) were Stage I; six patients (17%) were Stage II; three patients (8%) were Stage III; and 13 patients (36%) were Stage IV. Nine patients (25%) were treated with external radiation and interstitial implant; seven patients (20%) were treated with interstitial implant alone; nine patients (25%) were treated with external radiation alone and 11 patients (30%) with external radiation and intracavitary radiation. The five year NED survival was 71% in Stage I, 66% in Stage II, 33% in Stage III and 0% in Stage IV. This paper discusses radiotherapy management of primary carcinoma of the vagina.

A versatile permanent planar implant technique utilizing iodine-125 seeds imbedded in gelfoam.

Tumors attached or adjacent to critical structures can often not be completely resected or resected with adequate surgical margins. Sites involving major blood vessels, the vertebral column or the brain with small residual tumors or suspicious margins often present technical difficulties for standard I-125 or Ir-192 implants. A relatively simple, accurate and inexpensive implant method is described using I-125 seeds imbedded in gelfoam to implant permanently into small residual tumors or suspicious margins where standard implant techniques may be unsatisfactory. A method for planning the treatment dose for such an implant is described. Cases involving paraspinal and brain tumors are reported to illustrate the technique.

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.

Treatment planning for permanent and temporary percutaneous implants with custom made templates.

Nine patients who were presented at MSKCC with primary or recurrent pelvic or head and neck tumors and for whom surgery or further external radiation were excluded, were treated with percutaneous permanent or temporary implants, with individual pre-treatment planning and custom made templates. The tumor dose distributions achieved were as good as for implants performed at the time of surgical exploration. No serious complications have been encountered.

Pleurectomy and intraoperative brachytherapy and postoperative radiation in the treatment of malignant pleural mesothelioma.

Forty-one patients with diffuse, pleural mesothelioma limited to one hemi-thorax underwent a thoracotomy at Memorial Sloan-Kettering Cancer Center from January 1976 to July 1982. Treatment at thoracotomy consisted of as complete a parietal pleurectomy as was possible to remove the bulk of the tumor. Measurable gross residual disease was treated whenever feasible, with permanent 125I implantation; residual diffuse disease was treated by a temporary 192Ir implantation or by postoperative instillation of 32P. External radiation therapy was given 4-6 weeks postoperatively to the involved hemi-thorax, shielding the lung and utilizing a combination of electron and a photon beam. A dose of 4500 rad in 4.5 weeks was given to the pleural surface by the mixed beam. There was no postoperative mortality in this group of 41 patients. Complications developed in 6 patients (15%). The median survival was 21 months; the one year survival was 65% and the two year survival was 40%. The median disease-free survival was 11 months and the one and two year disease-free survival 44 and 13% respectively. This study suggests that the combination of pleurectomy, intraoperative brachytherapy and postoperative external radiation increased the local control of the tumor and prolonged the survival.

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.

Role of brachytherapy in the management of desmoid tumors.

From 1977 to 1982, fourteen patients with desmoid tumors underwent surgery and brachytherapy. Surgery ranged from biopsy to complete or partial excision of the tumor. Most of these patients had locally advanced tumor or positive margins. A high recurrence rate is expected in such a group if treated by surgery alone. In twelve out of fourteen patients the treatment was considered curative when all disease sites could be encompassed. In the remaining two patients the treatment was considered palliative because the tumor encroaching on to the spinal cord was left untreated. Ten out of twelve curatively treated patients have remained free of recurrence at a minimum of 2 year follow-up. Five of them were followed from 4-6 years. In the palliatively treated group, one patient is alive with active disease at 18 months. Three patients developed complications with wound healing. This experience suggests that surgery and brachytherapy treatment for desmoid tumor results in higher local control than expected from surgery alone in this selected group of patients.

Brachytherapy and function-saving resection of soft tissue sarcoma arising in the limb.

The treatment of soft tissue sarcoma of the limb by function-saving resection and brachytherapy (BRT) was systematically studied from 1975 to 1990 at the Memorial Sloan-Kettering Cancer Center, using iridium-192 temporary tumor-bed implants. Initial experiences showed an 88% local control rate in 33 patients who had locally advanced sarcomas, many of which would have required treatment by amputation. The technique also controlled 70% of tumors that abutted or invaded a major neurovascular bundle that was dissected out and preserved. A prospective randomized study (BRT vs no BRT) confirmed the highly significant efficacy of BRT in preventing local recurrence. This salutary effect is mainly seen in high-grade tumors. Major complications of wound healing occurred in the earlier years of this experience. Adoption of improved techniques of surgical wound repair, standardization of radiation dose planning, and in particular, postponing the loading of radiation sources until after the fifth postoperative day has reduced the rate of serious wound complications, to a level not significantly different from that seen after surgical resection alone. These results rival those currently achieved in centers experienced in external beam therapy of soft tissue sarcomas, and offer the advantage of completion of treatment in one relatively short hospital stay.

Preclinical studies with the photon radiosurgery system (PRS).

PURPOSE: Determine the radiobiological effectiveness (RBE) for low-energy X-rays (average energy of 23 KeV) produced by the Photon Radiosurgery System (PRS). METHODS AND MATERIALS: RBE values were assessed by comparison with survival data obtained for cells irradiated with either low-energy X-rays from a GE Maxitron 100 machine or high-energy photons from a clinically used Varian 6 MV LINAC. The output of the GE and PRS sources was determined using Baldwin-Farmer and Markus thin window ionization chambers calibrated with 50 kVp X-rays and cross-checked against figures supplied by Photoelectron Corporation. The dose-rate for the PRS was 1.2 Gy/min at a distance of 35 mm with a field flatness of +/-2%. RESULTS: The RBE for the PRS low-energy X-ray source (at 1-mm depth) was greater than either the GE or Varian machines and varied with cell survival. For Chinese hamster ovary (CHO) cells, the PRS was 1.25 and 3.3 times more effective than 90 kVp X-rays and 6 MeV photons at 0.5% cell survival, respectively; by comparison, the PRS was 1.2 and 1.9 times more effective at 0.05% cell survival, respectively. Similar RBE values of 1.4 and 1.2 were obtained for human U373 and T98 glioblastoma cells grown in vitro irradiated with the PRS or GE sources, respectively. Other studies showed that the RBE for the PRS low-energy X-ray source increased with depth. The RBEs for the PRS source at 1-mm and 4-mm depth were 1.2 and 2.5 (0.5% survival) and 1. 2 and 1.9 (0.05% survival). CONCLUSIONS: The biological and physical properties of the PRS low-energy X-rays offer, under the right conditions, a significant advantage for patient treatment over conventional external beam, stereotactic, or brachytherapy treatment.