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.

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.

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.

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.

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.

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.

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.

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.

Combined surgery and radiation in endometrial carcinoma: an analysis of prognostic factors.

From 1969 to 1979, 300 patients with the diagnosis of endometrial cancer operated elsewhere were referred for treatment to the Department of Radiation Oncology at Memorial Sloan-Kettering Cancer Center. All the patients were staged according to FIGO classification. One hundred and seventy-three patients were Stage IA, 105 patients were Stage IB, and 22 patients were Stage II. Within Stage IA, 141 patients had well differentiated tumor (G1), 20 had moderately well differentiated tumor (G2), and 12 patients had poorly differentiated (G3). One hundred and thirty-three patients had superficial myometrial invasion and 40 patients had deep myometrial invasion. Within Stage IB, 69 patients had G1 tumor, 23 had G2, and 13 had G3 tumors. Seventy-four patients in this group had superficial myometrial invasion and 31 patients had deep myometrial invasion. Two hundred and eighty-three patients had adenocarcinoma, 13 patients had adenoacanthoma, 4 patients had adenosquamous and other histological types. All of the patients received combined surgery (total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO) and radiation. The radiation treatments consisted of external pelvic radiation and intravaginal vault radiation. External pelvic radiation was delivered with a megavoltage apparatus for a total dose of 4,000 cGy in 4 weeks preoperatively (47 patients) or postoperatively (105 patients) in patients presenting with high grade (G2,G3), more than 1/3 myometrial invasion, Stage II and extrauterine extension of disease at surgery. All patients received in addition, postoperative intravaginal vault irradiation consisting of 2100 cGy in 3 fractions over 4 weeks with a high dose rate remote afterloading technique. The follow-up in these patients ranged from 5-14 years. Survival data was calculated according to Kaplan-Meier Method and Cox regression multivariate analysis to identify the prognostic factors. The 10-year survival rate in Stage IA was 91%; in Stage IB 75%; and in Stage II it was 71%. Eleven patients (4%) developed recurrent disease with either local and/or distant metastasis. Nine-percent of the patients developed mild to moderate complications which resolved with conservative treatment. Patients with gross extra-uterine pelvic extension of disease had a poor survival compared with those presenting with microscopic involvement (40% vs. 80% at 5-years). No statistically significant difference in survival was observed between patients who received either preoperative or postoperative external pelvic irradiation.(ABSTRACT TRUNCATED AT 400 WORDS)

Technique for external beam treatment for mesothelioma.

A combined photon-electron beam treatment for diffuse pleural mesothelioma is discussed in this paper. The technique consists of parallel opposed 10 MV X rays prescribed to 4250 cGy using customized blocks to shield the lung. The pleura is then boosted with electrons to a dose of 3600 cGy. The combination yields a TDF of 74 ret to the pleura. As discussed in an earlier paper, this treatment method when combined with subtotal pleurectomy and I-125 implantation leads to improved survivals with minimal complications. The details of this 3-dimensional radiation treatment method were not described in detail. To improve target coverage and local control, the technique has been modified. CT is now used along with simulation plane films to define the entire pleural surface. The target volume has also been extended from the dome to the base of this diaphragm. These changes have led to improved pleural dose distributions; by blocking the liver or stomach, and boosting the crus of the diaphragm with electrons, there is little added morbidity. As is demonstrated by dose volume histograms, we have been able to deliver 4250 cGy +/- 10% to most of the pleura with 1/3 of the lung parenchyma receiving less than 2100 cGy.

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.

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.

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.

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.

The effect of local control on metastatic dissemination in carcinoma of the prostate: long-term results in patients treated with 125I implantation.

The study evaluates the effect of the locally recurring tumor on the incidence of metastatic disease in early stage carcinoma of the prostate. The probability of distant metastases was studied in 679 patients with Stage B-C/N0 carcinoma of the prostate treated at MSKCC between 1970 and 1985 (median follow-up of 97 months). Patients were staged with pelvic lymph node dissection and treated with retropubic 125I implantation. The actuarial distant metastases free survival (DMFS) for patients at risk at 15 years after initial therapy was 37%. Cox proportional hazard regression analysis of covariates affecting the metastatic outcome showed that local failure, used in the model as a time dependent variable, was the most significant covariate, although stage, grade, and implant volume were also found to be independent variables. The relative risk of metastatic spread subsequent to local failure was 4-fold increased compared to the risk without evidence of local relapse. The 15-year actuarial DMFS in 351 patients with local control was 77% compared to 24% in 328 patients who developed local relapses (p less than 0.00001). The relation of distant spread to the local outcome was observed regardless of stage, grade, or implant dose. Even stage B1/N0-Grade I patient with local control showed a 15-year actuarial DMFS of 82%, compared to 22% in patients with local relapse; p less than 0.00001). The median local relapse-free survival (LRFS) in the 268 patients with local recurrences who did not receive hormonal therapy before distant metastases were detected was 51 months, compared to a median of 71 months for DMFS in the same patients (p less than 0.001), consistent with the possibility that distant dissemination may develop secondary to local failure. Furthermore, distant metastases in patients with local control, apparently already existing as micrometastases before treatment, were detected earlier (median DMFS of 37 months) than in patients with local relapse (median DMFS of 54 months; p = 0.009). These data suggest that the existence and re-growth of local residual disease in localized prostatic carcinoma promotes an enhanced spread of metastatic disease, and that early and complete eradication of the primary tumor is required if a long term cure is to be achieved, although the clinical expression of secondary metastases may not become apparent for 6.5 years or more in one-half of the patients.

Permanent interstitial implantation using palladium-103: the New York Medical College preliminary experience.

Palladium-103 is a low energy photon emitter available for permanent interstitial implantation. Pd-103 has energy and safety characteristics similar to Iodine-125, but its initial peripheral dose rate is approximately three times greater. This may provide improved control of rapidly proliferating tumors. At the Westchester Campus of New York Medical College, 15 patients with residual or recurrent unresectable lesions were implanted with Pd-103. There were five males and 10 females with an age range of 41 to 93 years (median 58). Implanted sites included the chest wall, nasopharynx, vagina, and zygomatic region. Peripheral doses ranged from 55 to 203 Gy (median 107 Gy). A complete response was achieved in eight patients and a partial response in seven patients, for an overall response rate of 100%. We noted improved control with smaller volumes and peripheral doses at or above 115 Gy. No unusual skin or mucosal reactions were recorded. Possible advantages of Pd-103 as a substitute for I-125 include improved control of rapidly proliferating tumors and a more rapid clinical response of lesions. Disadvantages include current higher cost and an impracticality in maintaining a running inventory because of the short half-life of the isotope. Our experience suggests that Pd-103 is an attractive alternative to I-125.

Therapy and prognosis of testicular carcinomas in relation to TNM classification.

Eight-hundred and thirty-one patients with testicular carcinomas, either teratocarcinoma (405), embryonal carcinoma (406) or pure choriocarcinoma (20), treated mainly at our center from 1950 to 1976, were clinicopathologically staged according to the TNM Classification. The cancer was confined to the body of testis alone (T1 N0 M0) or extended to paratesticular structures (T2-4 N0 M0) in 37% of all patients. Para-aortic lymph nodes were found involved (N1-3) in 33% and juxtaregional lymph nodes (N4) in 9% of patients; distant metastases were detected initially in the lung alone (M1) and other distant organs (M2) in 21% of the patients. Postorchiectomy treatment was retroperitoneal lymphadenectomy with or without regional-juxtaregional irradiation and systemic chemotherapy in 470 patients; the other 361 patients received external irradiation and/or adjuvant chemotherapy. Survival determined at 5 years was 58% in teratocarcinoma cases, 41% in embryonal carcinoma cases and 0% in pure choriocarcinoma cases. Rates of 5-year survival according to the TNM staging were 81% for T1 N0 M0 tumors, 58% for T2-4 N0 M0 tumors, 44% for N1-3 M0 tumors, 33% for N4 M0 tumors and 10% for N0-4 M1 or 2 tumors. In patients who underwent lymphadenectomy with or without external irradiation, the 5-year survival rates with and without adjuvant chemotherapy, respectively, were 96% and 86% for T1 N0 M0 tumors, 100% and 60% for T2-4 N0 M0 tumors, 66% and 42% for N1-3 M0 tumors, 54% and 40% for N4 M0 tumors and 38% and 0% for N0-4 M1 tumors. In patients treated by external irradiation alone or following lymphadenectomy the rates of 5-year survival with versus without adjuvant chemotherapy were 100% versus 66% for T1-4 N0 M0 tumors, 44% versus 18% for N1-3 M0 tumors, 41% versus 22% for N4 M0 tumors and 3% versus 4% for N0-4 M1-2 tumors.

Improved response of a murine fibrosarcoma (Meth-A) to interstitial radiation when combined with hyperthermia.

Removable Iridium-192 implants provided a dose of 10 Gy/day or 41.5 cGy/hr at 0.5 cm from the center of 1.0 cm diameter tumors. The total radiation (x) alone was 20, 40 or 60 Gy, representing 2, 4, or 6 days of continuous radiation. The doses used for the combined treatments at elevated temperatures were 10, 20 or 30 Gy. The local tumor hyperthermia (LTH) treatment (43.6 for 35 min, water bath) was administered once for each 10 Gy of dose. The combined radiation + LTH was clearly superior to that achieved with radiation or LTH alone and yielded Thermal Enhancement Ratios (TER) of 3.4-3.9. Local tumor control rate was 67% and 89% for the 20 and 30 Gy x + LTH groups, respectively. A comparison of the results obtained in this study with those of earlier studies on the same tumor system indicate that the effects of Iridium-192 alone on this rapidly proliferating tumor were comparable to similar total doses of fractionated external beam radiation. Iridium + LTH produced a tumor response comparable to that achieved with external fractionated radiation + LTH. Combined treatment effect of elevated temperature appears to be less dose rate dependent in the range of 40 cGy/hr to 100 cGy/min and more dependent upon total dose accumulation.

Consensus guidelines for high dose rate remote brachytherapy in cervical, endometrial, and endobronchial tumors. Clinical Research Committee, American Endocurietherapy Society.

PURPOSE: A large number of medical centers have recently instituted the use of High Dose-Rate Afterloading Brachytherapy (HDRAB). There is wide variation in treatment regimens, techniques, and dosimetry being used and there are no national standard protocols or guidelines for optimal therapy. METHODS AND MATERIALS: The Clinical Research Committee (CRC) of the American Endocurietherapy Society (AES) met to formulate consensus guidelines for HDRAB in cervical, endometrial, and endobronchial tumors. CONCLUSION: Each center is encouraged to follow a consistent treatment policy in a controlled fashion with complete documentation of treatment parameters and outcome including efficacy and morbidity. Until further clinical data becomes available, the linear quadratic model can be used as a guideline to formulate a new HDR regimen exercising caution when changing from a Low Dose Rate (LDR) to a HDRAB regimen. The treatments should be fractionated as much as practical to minimize long term morbidity. As more clinical data becomes available, the guidelines will mature and be updated by the Clinical Research Committee of the AES.