Bernard Pierquin

Radical radiation therapy of breast cancer

Abstract The 5 year results of radical radiation therapy in operable, infiltrating breast cancer (T1, T2, T3; NO, N1a, N1b) in 177 patients are presented. The treatment protocol included a pre-radiotherapy tumorectomy for T1 and certain T2 tumors (those less than 3cm diameter). Patients with larger tumors were treated by radiotherapy alone. The treatment technique incorporated both conventional fractionated radiotherapy (60 Co and electrons) and endocurietherapy (192 Ir). At 5 years, the uncorrected, disease-free survival rates were 84 % for T1, 79% for T2 and 56% for T3: loco-regional persistent or recurrent disease was seen in 4.5 % of patients with Tl disease, 7.5 % of those with T2, and 23 % of T3 patients; 16 mastectomies had been performed. Of the patients with T1 and T2 disease, 95 % had retained their breast and the esthetic result was judged to be good in 75 %. We recommend this technique of radical radiotherapy in early breast cancer because of this high rate of tumor control, associated with a low rate of normal tissue damage and survival figures comparable to those achieved by radical surgery.

Salvage irradiation of oropharyngeal cancers using iridium 192 wire implants: 5-Year results of 70 cases

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.

Effect of dose rate on local control and complications in definitive irradiation of T1-2 squamous cell carcinomas of mobile tongue and floor of mouth with interstitial iridium-192.

From 1971 to 1988, 134 T1 and 145 T2 biopsy-proven squamous cell carcinomas of mobile tongue and floor of mouth were definitively managed by iridium-192. Implantations were performed using either guide gutters or afterloading plastic catheters. The prescribed dose at the reference isodose (85% of the basal dose rate, Paris system) was 60-70 Gy. Total dose was not adjusted to dose rate or tumor volume. Results of the 279 implants have been analysed to look for a possible influence of dose rate on local control and necrosis. Follow-up patients free of local recurrence is 1-180 months with average of 51 months. The 279 tumors were divided in four groups according to dose and dose rate: greater than or equal to 62.5 Gy and greater than or equal to 0.5 Gy/h (n = 130), greater than or equal to 62.5 Gy and less than 0.5 Gy/h (n = 36), less than 62.5 Gy and greater than or equal to 0.5 Gy/h (n = 81), less than 62.5 Gy and less than 0.5 Gy/h (n = 32). The four groups were comparable according to age, sex, tumor diameter and macroscopic aspect. At 5 years, the estimated local control (Kaplan Meier) was 93, 87, 79 and 52%, respectively (dose adjusted to dose rate: p less than 0.001, dose rate adjusted to dose: p less than 0.01, Log-rank); the necrosis rate was 44, 24, 37 and 5%, respectively (dose adjusted to dose rate: p = 0.08, dose rate adjusted to dose: p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Locoregional recurrences following radical external beam irradiation and interstitial implantation for operable breast cancer—a twenty three year experience

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.

Combined external irradiation and interstitial implantation for T1 and T2 epidermoid carcinomas of base of tongue: The creteil experience (1971–1981)

Forty-eight patients with T1 or T2 epidermoid carcinomas of the base of tongue were treated at the Henri Mondor Hospital between 1971 and 1981. Forty-one patients received moderate dose 60Co external beam irradiation (mean: 48.6 Gy) to the primary tumor and regional nodes, followed by an interstitial iridium 192 implant to the primary tumor (mean: 32 Gy). This completed the treatment for the 30 node negative patients, but those with clinically positive nodes were managed by either an additional electron beam boost to the involved nodes or a neck dissection. Seven tumors were treated exclusively by implantation to the base of tongue (mean: 63 Gy). Five-year crude disease-free survival is 50% with 35% of patients dying of recurrent disease. Definitive local control for T1 lesions is 85% (11/13) and for T2 is 71% (25/35). A dose response effect was observed with local control of 79% (26/33) obtained with a combined dose greater than or equal to 75 Gy, but only 50% (4/8) for less than or equal to 70 Gy. For N0 patients definitive regional control is 97% and for N1-3 is 89%. Minor or moderate soft tissue ulceration was observed in 12 patients, including 3 cases that progressed to osteonecrosis. None required surgical intervention. No correlation exists between necrosis and tumor size or total dose.

Iridium 192 implantation of T1 and T2 carcinomas of the mobile tongue

Between 1970 and 1986, 166 patients with T1 or T2 epidermoid carcinomas of the mobile tongue were treated by iridium 192 implantation (70 T1N0, 83 T2N0, 13 T1-2 N1-3). Five-year actuarial survival was 52% for T1N0, 44% for T2aN0, and 8% for or T1-2 N1-3. Cause specific survivals were 90%, 71%, and 46%, respectively. Local control was 87% for both T1N0 and T2N0, and 69% for T1-2 N1-3. Seven of 23 failures were salvaged by surgery, increasing local control to 96% for T1 and 90% for T2. Thirty-six patients developed a minor or moderate necrosis (16% T1, 28% T2). Half of these involved bone but only five required surgical intervention. Both local control (LC) and necrosis (nec) increased with increasing dose but improvement beyond 65 Gy is minimal (less than or equal to 60 Gy: LC = 78% nec = 13%; 65 Gy: LC = 90% nec = 29%; greater than or equal to 70 Gy: LC = 94% nec = 23%). For N0 patients, neck management consisted of surveillance (n = 78), elective neck dissection followed with external irradiation for pathologically positive nodes (n = 72), or irradiation (n = 3). Clinically positive nodes (13 patients) were managed by either neck dissection followed by external irradiation if pathologically positive (n = 10) or irradiation alone (n = 3). Regional control was 79% for N0 patients, improving to 88% after surgical salvage, and was 9/13 for N1-3 patients. We recommend that T1 and T2 carcinomas of the mobile tongue be treated by iridium 192 implantation to deliver 65 Gy. Mandibular necrosis should be reduced by using an intra-oral lead-lined dental mold.

Conservative treatment of breast cancer in Europe: Report of the Group Européen de Curiethérapie

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)

Prognostic factors of local outcome for T1, T2 carcinomas of oral tongue treated by iridium 192 implantation

The results of Iridium 192 implantation for 121 node negative T1 or T2 squamous carcinomas of mobile tongue were reviewed to look for predictors of local control and necrosis. Age, sex, total dose, dose rate, linear activity, and intersource spacing were examined. Minimum follow-up was 2 years but no patient with local recurrence or necrosis was excluded. There were 57 T1N0 tumors, 45 T2aN0 (2.1-3.0 cm), and 19 T2bN0 (3.1-4.0 cm). Local failures occurred in 14% of T1, 11% of T2a, and 26% of T2b. Univariate analysis showed that local control increased with increasing dose (55-60 Gy: 73%; 65-75 Gy: 92%, p = 0.005), whereas multivariate analysis revealed both sex and total dose to be significant. Radiation necrosis occurred in 17% of T1, 29% of T2a, and 47% of T2b (p = 0.034). Half were limited to soft tissue and the majority healed with conservative management. Univariate analysis showed that necrosis increased with increasing dose (55-60 Gy: 16%; 65-75 Gy: 33%, p = 0.037), as well as increasing dose rate, linear activity, and intersource spacing. With multivariate analysis only stage, dose rate, and spacing remained predictive of necrosis. Total dose was not adjusted for dose rate or tumor volume. This analysis suggests that within the therapeutic range of low dose rate brachytherapy, correction of total dose according to dose rate is unnecessary. We recommend 65 Gy. Lower dose rate (0.4-0.5 Gy/hr) and closer intersource spacing (12-14 mm) should be aimed for to minimize necrosis.

Comparison of curietherapy versus external irradiation combined with curietherapy in Stage II squamous cell carcinomas of the mobile tongue

One hundred and ten patients with Stage II epidermoid carcinomas of the mobile tongue were treated by interstitial irradiation (Group I: 85 patients) or external irradiation to the primary and the regional lymphatics followed by an interstitial boost (Group II: 25 patients). The neck was managed by either an elective neck dissection (43 patients) completed by external irradiation in 13 patients with pathological specimen or close follow-up (40 patients) with therapeutic neck dissection for relapses (7 patients) in Group I. Primary local control was 88% in Group I and 36% in Group II. Regional control was 91% in Group I and 5/6 in Group II for patients whose primary tumor was controlled. Five-year absolute disease-free survival (DFS) was 42% in Group I and 24% in Group II, but there was an imbalance in the distribution of larger tumors favoring Group I. There were 30 radiation-induced complications and four patients required corrective surgery. This retrospective analysis showed better results in patients whose primary was treated by interstitial irradiation alone which has the extra advantage of preserving salivary function.

Interstitial radiation therapy for carcinoma of the penis using iridium 192 wires: the Henri Mondor experience (1970-1979)

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.