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Between February 1979 and January 1982, a Phase II study of misonidazole as a radiosensitizer was performed in 34 patients with advanced carcinoma of the uterine cervix. Twenty-nine patients were treated with conventional fractionated radiation and five patients with a twice daily fractionation schedule, 3 days a week. The total dose to the whole pelvis was 5000 cGy delivered in 5.5 weeks. Intracavitary curietherapy delivered an additional boost to the tumor. Misonidazole was given to all patients during external radiation and to 25 patients during intracavitary treatment for a total dose of 11 to 14 g/m2. All patients were followed for at least 28 months after treatment with a median follow-up of 52 months. Misonidazole toxicity included peripheral neuropathy (18%) and central nervous system toxicity (3%). The 3-year survival rate is 74% and the 3-year disease-free survival is 57%. When compared to our historical group survival, 42 and 12% for Stage III and IV, respectively, our data suggest that there is a probable advantage from using misonidazole in advanced carcinoma of the cervix.

From July 1971 to December 1981, 33 selected patients with T1, T2 tumors of the tonsillar region were treated according to the following protocol: 1. Telecobalt therapy to the primary site and to neck nodes to a dose of 45 Gy. 2. Brachytherapy to the primary site to a dose of 30 Gy using iridium 192. 3. Boost dose to involved neck nodes with electrons, or radical neck dissection, whether N1, N2, or N3. The actuarial disease-free survival was 76% when all patient groups were included and 80% for the N0 patients. The local control rate was 100%. Disease control in the neck was 94% overall and 100% for the N0 group. These results favor the use of this protocol for superficial, minimally infiltrating tumors less than 4 cm in diameter, without obvious extension to the base of the tongue or retromolar trigone.

From 1977 to 1984, we treated 34 patients with mycosis fungoides and 9 patients with B cutaneous lymphomas. Eighteen patients with mycosis fungoides were treated with total skin electron irradiation (TSEI) and had a minimum follow-up of 15 months (range 15 months to 7 years). The lowest electron energy of the linear accelerator was 8 MeV therefore we placed a plexiglas screen between the patient and the machine; the resulting electron energy was 4 MeV. The total dose was 30 Gy delivered in 12 fractions over 40 days. There were 8 males and 10 females. The median age was 48 years (ranging from 13 to 78 years). All patients were staged as follows: Stage A = superficial lesions covering less than 50% of the body surface; Stage B = superficial lesions covering more than 50% of the body surface; Stage C = tumors involving the skin, lymph nodes and/or visceral organs. Five patients with Stage A (5/5) and 5 patients with Stage B (5/5) had a complete remission, 1 stage A patient relapsed 6 months after completion of treatment. All the Stage B patients recurred between 3 and 15 months. The recurrences were localized to the skin and were well controlled with topical nitrogen mustard or puvatherapy. Among the Stage C patients, 3 did not respond to treatment and died of their disease; the remaining 5 patients achieved complete remission but they all relapsed from 2 to 9 months following completion of treatment. The median follow-up was 32 months and the average time for relapse was 6.5 months. All relapses except one (15 months) occurred within the first year. We feel that total skin electron irradiation is indicated in Stage A and B patients. However, we feel Stage C patients should receive TSEI for palliative purposes only.

A series of 93 cases of endometrial adenocarcinoma stage I, of which 87 were treated by surgery in combination with pre- or postoperative irradiation, is analysed with respect to recurrence rate, survival and effect of preoperative irradiation on myometrial invasion. According to the authors, the treatment of choice remains a combination of surgery and radiation therapy in order to control the primary tumor and prevent vaginal recurrence. The authors recommend uterovaginal intracavitary irradiation followed by total abdominal hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy, and with adjunctive postoperative external irradiation reserved for the rare cases at high risk for locoregional failure (persistence of deep myometrial invasion, lymph node involvement).

In preparation for the 18th meeting of the European Curietherapy Group, devoted to cancer of the lip, 2 363 cases of lip cancer from 23 European Hospitals were retrospectively analysed. After presentation of these results, several free communications, and a large interdisciplinary panel discussion, a consensus was reached for the management of the primary tumor and the regional lymph nodes. Interstitial implant with iridium 192 wires results in a local recurrence rate which does not excede 3,4%. This method may be considered the treatment of choice for T1 and T2 tumors and many T3 tumors. On the other hand surgery should be used for in situ tumors and very large deeply infiltrating tumors. As the 2% failure rate after routine prophylactic neck dissection does not significantly differ from the 3% failure rate when patients undergo neck dissection only if clinically positive neck nodes develop, patients with T1, T2 tumors and no palpable neck nodes, who can be expected to submit to regular follow-up examination, may be managed conservatively. Patients with clinically positive neck nodes should undergo a neck dissection followed by radiationtherapy.

63 patients with Hodgkin disease of limited extent (I, II, III) are treated with two protocols: extended field irradiation versus chemotherapy (M.O.P.P.) + extended field irradiation. Three points are suggested by analysis of the results: 1) Advantage from the combination of chemotherapy-radiotherapy. 2) Resistance to chemotherapy frequent innodular sclerosis. 3) In patients treated with chemotherapy the reaction has a prognostic value: failure of treatment being seen only in patients who did not obtain a complete remission.

These two meetings organised successively to discuss the conservative methods of treatment of breast cancer, made it possible to gather data on a substantial number of patients from an important number of European centers. It is encouraging to note that there is a general consensus among the various European centers concerning the basic principles of treatment and that long years of experience have led to the use of well defined technical protocols which are relatively similar from one center to another. Since serious complications have now become exceptional, we foresee that the conservative treatment of breast cancer will continue to evolve on a technical level as the indications for this approach continue to develop within the overall plan of patient care with the assurance that optimum results may be maintained. However, we must point out that the lack of a unified system of reporting irradiation doses in volumes corresponding to the possible and/or real extension of the tumor remains an obstacle in developing a truly unified attitude in the application of these techniques. Each center defines the radiation dose given by wide field techniques and the dose given by cone-down (boost) techniques in a relatively arbitrary way without true anatomic correlations. These correlations must be found and defined, so that a specified dose has a universal meaning. The role of the surgeon in the successful application of breast conserving techniques is far from negligible. Now that our colleagues who wield the scalpel have begun to gain confidence in the curative powers of irradiation, we may hope that a close collaboration between radiotherapist and surgeon will lead to the application of conservative techniques under optimal conditions in the breast, with the development of minimal tumorectomy and minimal curative cone-down dose; and in the axilla, with the development of axillary dissection limited to the lower border of the pectoralis minor and followed by radiation therapy only if more than two nodes show tumor involvement. However, it is important to point out that while it is possible to use radiation therapy alone to treat breast cancer and conserve the breast at all stages of the development of the disease, it is not possible to use conservative surgical techniques alone as a substitute for adequate irradiation. The development of protocols which routinely apply breast conserving methods in synonymous with the development and routine use of the best radiation therapy techniques. This article presents two separate and complementary studies of two different sets of data presented at two successive meetings.(ABSTRACT TRUNCATED AT 400 WORDS)

From 1970 to 1984, 127 patients with T1 or T2 carcinomas of the oropharynx were treated with external irradiation to the primary tumor and neck nodes to a dose of 45 Gy, followed by a further 30 Gy delivered by an iridium 192 implant to the primary tumor. Patients with clinically positive nodes had either further neck irradiation using electrons or a neck dissection. Crude 5-year disease-free survival was 66% for tonsillar carcinomas, 43% for soft palate, and 51% for base of tongue. Local control was 98%, 85%, and 76%, respectively. Regional control was 97% for N0 patients and 88% for N1-3. Soft tissue ulceration occurred in 17 patients; all healed spontaneously. The high rate of local control achieved in these patients while preserving function and minimizing xerostomia supports the use of this approach.

From 1975 to 1982, 597 patients with localized prostatic adenocarcinoma were treated using external beam irradiation in one of 6 cooperating centers. The mean patient age was 67 years. The 5 and 10 years actuarial survivals (including all causes of death) were 70% and 40% respectively. The adjusted survival rates become 86% at 5 years and 61% at 10 years when only death due to cancer is taken into consideration. Despite the fact that patients with stage A1 and A2 disease show different patterns of lymphatic spread, the actuarial and adjusted 8 years survivals were identical for both staging groups, in this study, 57% and 90%, respectively. It is significant that the majority of patients in both group A1 and in group A2 received irradiation to the pelvic lymph nodes as well as the prostate. Patients with stage B1 disease showed a 7 years actuarial survival of 53% and an 82% survival adjusted for death due to cancer only. Patients in both group B2 and group C, showed an identical 10 year actuarial survival rate of 49%. However, without CT scanning, it is difficult to differentiate between these 2 staging groups. Patients with stage C2 disease showed 10 years actuarial and adjusted survival rates of 20% and 40% respectively. The local recurrence rate after primary radiation therapy did not exceed 11% in any patient group. These data demonstrate, once again, that the dogma pertaining to the radioresistance of prostatic cancer is outdated.

From April 1971 to October 1984, 71 patients with T1 or T2 tumors of the faucial arch were treated according to the following protocol: Telecobalt therapy to the primary site and to the neck nodes to a dose of 45 Gy. Brachytherapy to the primary site to a dose of 25 to 30 Gy using iridium 192. For node positive patients, boost dose to involved neck nodes with electrons, or radical neck dissection. Seven patients with T1N0 tumors were treated exclusively by 60 Gy iridium implantation. The crude disease free survival is 66% for the group of patients with tumors of the tonsillar region and 41% for those with tumors of the soft palate or uvula. Local control of tonsillar tumors was 98% while that of tumors of the soft palate was 85%. Regional control was 98% for the N0 group and 87% for the N1-3 group. Five cases of soft tissue ulceration were observed, all of which healed spontaneously within a few months. Less salivary impairment was seen than after treatment by external irradiation alone. While these promising results have encouraged the use of this protocol, the introduction of the plastic tube technique has expanded the indications to include almost all T1 and T2 tumors of the faucial arch without obvious extension to the base of tongue or retromolar trigone.

Before loco regional treatment for head and neck cancer forty eight patients received one or the other of the following combined chemotherapy regimens: Regimen A (28 patients): high dosage methotrexate, bleomycin, cis-platin; regimen B (20 patients): common dosage methotrexate, bleomycin, hydroxyurea, vincristin. The effectiveness of regimen A seemed better than that of regimen B (46% responses versus 20%). This assessment must be accepted with caution, since, although the organization of treatment was strictly similar in the two groups, the study was not randomized, and there were noticeable differences between the two groups. Regimen B was associated with no toxicity. Regimen A was responsible for two fatalities. These two cases were linked to high dosage methotrexate. However, a combined chemotherapy regimen of type A with the high dosage methotrexate replaced by intermediate dosage methotrexate, seems feasible to us. Loco regional treatment was not impaired by initial chemotherapy with either regimen.

Between May 1971 and November 1980, 70 patients with recurrent or new oropharyngeal cancers arising in previously irradiated tissues were treated using iridium 192 afterloading techniques. The actuarial local control was 72% at 2 years and 69% at 5 years. Although local control of the tumor was achieved in the majority of these patients, only 10 patients remained alive at 5 years (14%). Patients with lesions of the faucial arch and posterior pharyngeal wall had the best results; local control was achieved in 100% of these patients. Patients with lesions of the base of tongue and of the glosso-tonsillar sulcus had poorer results; local control was achieved in 61%. Because these results compare favorably with the results of previously published series, we recommend re-irradiation with brachytherapy for recurrent or new malignancies arising in a previously irradiated oropharynx. When the lesion is located in the faucial arch, brachytherapy is the treatment of choice. When the lesion is located in the base of tongue, brachytherapy is a reasonable option.

Locoregional recurrences are reported in 493 consecutive with T1 T2 N0 N1 breast cancer patients who were treated with radical external beam irradiation and interstitial 192 Ir. implant between 1961 and 1979. Follow-up ranges from 5-23 years (mean 10 years) with 195 patients having 10-23 years follow up (mean 12 years). Tumorectomy was performed in 130/158 (88%) T1 and 73/335 (22%) T2 patients. There were 51 (10%) locoregional recurrences with 34 mammary, 14 combined mammary/axillary and 3 isolated axillary recurrences. The 10 year relapse rate was 20/195 (10%). The risk, timing and site of relapse varied according to TNM stage and tumorectomy. The risk was higher for T2 (42/335, 12.5%) than T1 (9/158, 5.5%) due to a larger number of recurrences occurring in the first 5 years (T2 32/335, 9.5% vs T1 4/158, 2.5%). Between 5-10 years, risk of relapse equalized to around 3% for both groups and only 1 relapse was seen after 10 years. Of the 48 mammary recurrences, 25 (52%) occurred in the implant volume, 7 (14%) occurred on the margin of the implant, 12 (25%) occurred at sites remote from the primary and in 4 (9%), the exact site could not be defined. 14/48 mammary recurrences were accompanied by axillary relapse, there were 3 isolated axillary recurrences and supraclavicular metastases accompanied axillary relapse in 3 cases. The overall risk, of axillary relapse was 3% (17/493) and there was significant correlation with initial N stage. Salvage surgery generally mastectomy and axillary dissection, was possible in 45/51 (90%) recurrences. 23/45 (50%) survive NED 0.2-9 years (mean 3 years) after salvage. 8/23 (35%) followed longer than 5 years after salvage survive NED. Our results have been compared with other series in the literature and changes in our current protocol are described.

A retrospective multicentric analysis of the results of irradiation of 1676 carcinomas of the skin of the nose and nasal vestibule was performed by the Groupe Européen de Curiethérapie (Tunis, May 1986). Overall local control was 93% with a minimum follow-up of 2 years. Local control is dependent on the tumor size (diameter less than 2 cm: 96%, 2-3.9 cm: 88%, greater than or equal to 4 cm: 81%), and tumor site (external surface of the nose: 94%, vestibule: 75%). Local control was independent of histology for smaller tumors, but for those larger than 4 cm, basal cell carcinomas were more frequently controlled than squamous cell carcinomas. Recurrent tumors are less frequently controlled than those being treated for the first time (88 vs. 95%). There were few complications and cosmetic results were generally satisfactory. The results of implantation, orthovoltage and megavoltage irradiation are compared with respect to local control, complication rate and cosmesis. Implantation is usually the treatment of choice for vestibular tumors but for those of the external surface the choice depends on the tumor diameter. Implantation and orthovoltage irradiation are equivalent for tumors less than 2 cm. For those from 2 to 3.9 cm, the results of orthovoltage irradiation may be satisfactory in a selected population but implantation is usually more suitable for tumors with rapidly changing contour.(ABSTRACT TRUNCATED AT 250 WORDS)

Small tumors of the mobile portion of the bladder may be treated by means of interstitial irradiation by iridium-192 wiring. Forty-four tumors (mostly T1, but also T2 and T3) were treated by this procedure and followed over five years. Good results are attained in 66 per cent of the cases. This method has the benefit of avoiding irradiation to the surgeon's hands, and of delivering to a specific site a dose of 6,000 rads. No bladder contraction was observed. Supplementary treatment by irradiation has to be considered in view of frequent recurrences of malignant bladder tumors after transurethral resection of partial cystectomy. In small cancers slightly infiltrating the bladder wall, many attempts have been made to replace tele-irradiation by interstitial irradiation. The latter delivers specifically high rad dosage to the involved area. Radium needles has been used in France by Darget before 1951 but evaluation of accurate dosage proved difficult. This material was dangerous to the surgeon's hands, and the procedure lead frequently to bladder sclerosis. This technique is currently used by Van der Werf-Messing in Rotterdam. She strongly advises preoperative tele-irradiation (3 X: 350 rads) to prevent tumor implants in the scar. An intravesical balloon filled with fluid radioisotope of gold-198 or cobalt-60 has been used for diffuse malignant papillary epithelioma. It was discontinued because of radiation cystitis and subsequent contraction of the bladder. Recently in well-limited tumors, Bloom and Wallace have used Tantalum-182 needles which have interesting physical properties (high energy and short half-life period) (2).

Between May 1971 and March 1982, 73 patients with either recurrent or subsequent squamous cell carcinomas arising in a previously irradiated oropharynx were treated using iridium 192 wires. Although local control was achieved in 72% of these patients, only 10 remained alive at 5 years (14%). Local control was best for tonsillar arch lesions (96%), while base of tongue and glosso-tonsillar sulcus tumors were controlled in only 60%. One of the two patients with a posterior pharyngeal wall lesion is alive and well at 5 years, while the other died of an unknown cause at 20 months. Salvage implantation produced soft tissue necrosis in 36% of base of tongue implants, but only 18% of those involving the tonsillar arch. Although one necrosis was fatal, the others were successfully managed medically. Since these results compare favorably with those of previously published series, we recommend re-irradiation with iridium 192 for recurrent or new malignancies arising in a previously irradiated oropharynx. For tonsillar arch lesions, brachytherapy is the treatment of choice while in the base of tongue, it is reasonable option.

From January 1970 to November 1982, 70 patients with carcinoma of the pinna were treated by interstitial irradiation. An afterloading technique with Iridium 192 wires was used. One patient recurred and had a total pinnectomy followed by 60 Gy external radiation. This patient was alive without evidence of disease at 134 months. Three patients who had tumors greater than 4 cm in size at presentation developed late necrosis which required subsequent total pinnectomy. Cosmetic results were assessed in 55 patients and were good with few late sequelae (in 78% of cases (36/46) when the tumor measured less than 4 cm, but only in 1/9 when the tumor measured more than 4 cm). We advocate interstitial Iridium 192 irradiation for treatment of pinna tumors smaller than 4 cm. None of 39 patients with squamous cell carcinoma had biopsy proven cervical lymph node metastasis at the time of diagnosis. Four patients with squamous cell carcinoma (4/39: 10%) later developed a regional nodal metastasis after treatment of the pinna. All four relapsed in the parotid region and were managed by partial parotidectomy and neck dissection followed by external irradiation. One of these four patients died from uncontrolled cervical node disease. In our opinion, when regular follow-up is dependable, it is reasonable to save treatment of the cervical nodes for those patients who relapse with involved metastatic cervical nodes.

We report the comparative results for local tumor control between two groups of patients treated by radiotherapy fractionated in a conventional manner at normal high dose rate (29 patients with 2 years minimum follow-up and 24 patients with 3 years minimum follow-up) and by low dose rate radiotherapy (19 patients with 2 years minimum follow-up, 14 patients with 3 years minimum follow-up) with moderately extensive cancers of the oropharynx (T2b-T3a, 3-5 cm in diameter). At 2 and 3 years follow-up, the number of local recurrences in the patients treated with low dose rate radiotherapy is half (26 and 21%) that for those treated with conventionally fractionated radiation at normal high dose rates (52 and 54%). These results require more rigorous confirmation.

From 1970 to 1979, a group of 50 patients was treated for squamous cell carcinoma of the penis by interstitial irradiation using an afterloading technique and iridium 192 wires. The group included 9 patients with T1 tumors, 27 with T2 tumors, and 14 with T3 tumors. Forty-five patients presented with no metastatic inguinal nodes (N0), 3 patients with N1 nodes, and 2 patients had N3 nodes. After treatment, 11 patients (1 T1, 6 T2 and 4T3) developed local recurrences; 10 of these 11 patients underwent penile amputation which controlled the tumor in 7 of the patients. One patient refused amputation. Three patients developed post-therapeutic necrosis which necessitated partial amputation in 2 cases. Eight patients developed post-therapeutic urethral stenosis, which required surgical treatment in three of the cases. Overall, at their last follow-up examinations, 74% of the patients were free of disease with conservation of penile morphology and function. Most patients without metastatic nodes (37/45) at diagnosis did not receive prophylatic treatment of the groin. Two of these patients developed delayed metastatic nodes; one was successfully salvaged. All 5 patients presenting with metastatic nodes at diagnosis died, four with uncontrolled regional disease. Twenty-one percent of the patients died of their disease. We advocate interstitial irradiation using iridium 192 wires for the treatment of non-infiltrating or moderately infiltrating squamous cell carcinoma of the penis in which the largest dimension does not exceed 4 cm. Pre-implant circumcision and regular long-term follow-up are necessary. More extensive tumors are better managed surgically. When regular follow-up can be assured, it is reasonable to forgo prophylactic treatment of the inguinal nodes in patients presenting without groin metastasis.

At the conclusion of our recently published article in this Journal on low dose rate irradiation in moderately extensive cancers of the oropharynx, we updated our results in May 1986. Here we report on an expanded group of 65 patients with a 2 year minimum follow-up; 32 patients were treated by low dose rate irradiation and 33 by conventional fractionation. Forty-four percent (14/32) low dose irradiation patients survived with NED vs 8/33 (24%) conventional fractionation patients. The highly significant differences in the level of local recurrences between patients treated by low dose rate irradiation, 5/32 (16%), compared with conventional fractionation, 20/33 (61%), highlights the enhanced efficacy of the low dose rate irradiation technique in the local cure of cancers of the oropharynx. This superior local control however is achieved at the cost of a number of necrosis, 5/32 (16%).

Records of 323 patients with TNM Stage M0 sarcoma of soft tissue treated by the Radiation Medicine Service of the Massachusetts General Hospital over a 14-year period were reviewed to study the incidence and the implication of regional lymph node involvement. Nineteen patients (5.9%) had evidence of sarcoma metastatic to draining lymph nodes, zero of 63 (0%) were Grade 1 sarcomas, two of 118 (2%) were Grade 2, and 17 of 142 (12%) were Grade 3 sarcomas. Among patients with Grade 3 sarcomas, rhabdomyosarcoma (five of 14), vascular sarcoma (two of five), and epithelioid sarcoma (four of five) were associated with a higher incidence of lymph node involvement than synovial sarcomas (zero of four), fibrosarcomas (zero of 16), malignant fibrohistiocytomas (one of 29), neurofibrosarcomas (one of eight), liposarcomas (one of 14), and leiomyosarcomas (one of ten). From the 19 patients who had evidence of metastatic nodes, six (32%) were alive more than 58 months after the treatment of the nodes; four of six patients were without further tumor. The data of this study are compared with those cited in a review of the literature.