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.     

Radiation therapy of squamous cell carcinoma of the nasal vestibule

From 1978 until 1988, 63 consecutive patients with squamous cell carcinoma of the nasal vestibule were treated by radiation therapy. Mean follow-up time was 46 months. Thirty-five patients were classified as having T1N0 tumors, 24 as T2N0; four patients were staged as T1/2N+. Treatment of the primary consisted of external radiation (n = 17), interstitial radiation (n = 37), or external radiation combined with interstitial radiation (n = 9). With respect to the N0 patients, local relapse was found in 3% (1/35) of T1 tumors and in 21% (5/24) of T2 tumors. Three out of six failures were salvaged by surgery. Elective irradiation of both sides of the neck (40 Gy) was performed in 9 T1 and in 16 T2 patients. Two regional failures occurred in the electively irradiated necks, two in the non-irradiated necks. Regarding the T1/2N+ patients, three relapsed locally and/or regionally, and one remains NED. For all 63 patients, a 5-year corrected survival of 90%, a relapse-free survival of 80%, and an overall survival of 65% were observed. In summary, for optimal local control and cosmesis we feel that for T1,2 N0 tumor stages a dose of 60 Gy for T1 and 70 Gy for T2 tumors is adequate treatment. The primary tumor is irradiated preferentially in our view, by means of interstitial techniques; furthermore, our data do not support the use of elective neck RT. Although patients rarely present with lymph node metastasis (6%), the prognosis of T1,2 N+ patients remains grim and more aggressive (surgical) treatment might be needed for this category.     

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.     

Irradiation in carcinoma of the vulva: factors affecting outcome

Purpose: This report reviews the increasing role of radiation therapy in the management of patients with histologically confirmed vulvar carcinoma, based on a retrospective analysis of 68 patients with primary disease (2 in situ and 66 invasive) and 18 patients with recurrent tumor treated with irradiation alone or combined with surgery.Methods and Materials: Of the patients with primary tumors, 14 were treated with wide local excision plus irradiation, 19 received irradiation alone after biopsy, 24 were treated with radical vulvectomy followed by irradiation to the operative fields and inguinal–femoral/pelvic lymph nodes, and 11 received postoperative irradiation after partial or simple vulvectomy. The 18 patients with recurrent tumors were treated with irradiation alone. Indications and techniques of irradiation are discussed in detail.Results: In patients treated with biopsy/local excision and irradiation, local tumor control was 92% to 100% in Stages T1-3N0, 40% in similar stages with N1-3, and 27% in recurrent tumors. In patients treated with partial/radical vulvectomy and irradiation, primary tumor control was 90% in patients with T1-3 tumors and any nodal stage, 33% in patients with any T stage and N3 lymph nodes, and 66% with recurrent tumors. The actuarial 5-year disease-free survival rates were 87% for T1N0, 62% for T2-3N0, 30% for T1-3N1 disease, and 11% for patients with recurrent tumors; there were no long-term survivors with T4 or N2-3 tumors. Four of 18 patients (22%) treated for postvulvectomy recurrent disease remain disease-free after local tumor excision and irradiation. In patients with T1-2 tumors treated with biopsy/wide tumor excision and irradiation with doses under 50 Gy, local tumor control was 75% (3 of 4), in contrast to 100% (13 of 13) with 50.1 to 65 Gy. In patients with T3-4 tumors treated with local wide excision and irradiation, tumor control was 0% with doses below 50 Gy (3 patients) and 63% (7 of 11) with 50.1 to 65 Gy. In patients with T1-2 tumors treated with partial/radical vulvectomy and irradiation, local tumor control was 83% (14 of 17), regardless of dose level, and in T3-4 tumors, it was 62% (5 of 8) with 50 to 60 Gy and 80% (8 of 10) with doses higher than 60 Gy. The differences are not statistically significant. There was no significant dose response for tumor control in the inguinal–femoral lymph nodes; doses of 50 Gy were adequate for elective treatment of nonpalpable lymph nodes, and 60 to 70 Gy controlled tumor growth in 75% to 80% of patients with N2-3 nodes when administered postoperatively after partial or radical lymph node dissection. Significant treatment morbidity included one rectovaginal fistula, one case of proctitis, one rectal stricture, four bone/skin necroses, four vaginal necroses, and one groin abscess.Conclusions: Irradiation is playing a greater role in the management of patients with carcinoma of the vulva; combined with wide local tumor excision or used alone in T1-2 tumors, it is an alternative treatment to radical vulvectomy, with significantly less morbidity. Postradical vulvectomy irradiation in locally advanced tumors improves tumor control at the primary site and the regional lymphatics in comparison with reports of surgery alone.     

Iridium-192 curietherapy for T1 and T2 epidermoid carcinomas of the floor of mouth

From 1970 to 1986, 117 patients with T1 (47) or T2 (70) epidermoid carcinomas of the floor of the mouth (SCC) were treated by iridium-192 implantation (192 Ir). The dose was prescribed according to the Paris System and varied over those years. Follow-up information was available on 116 patients. There were 46 T1N0, 47 T2N0, and 23 T2N1-3. Neck management varied for the 93 N0 patients consisting of surveillance (24 T1, 17 T2) or elective neck dissection (22 T1:all pN-, 30 T2: 20 pN-, 10 pN+). Cause specific survival rates were 94% for T1N0, 61.5% for T2N0, and 28% for T2N1-3 at 5 years. Primary local control was 93.5%, 74.5%, and 65%, respectively, and 98%, 79%, and 65% after salvage. Patients with gingival extension or a tumor size over 3 cm (T2b) had a local control of 50% (9/18) and 58% (15/26), respectively. Nodal control was 93.5% for Stage I, 85% for Stage II, and 48% for T2N1-3 patients. There was no difference in nodal control with regard to treatment policy for Stage I-II patients. There were few complications including three deaths: two from surgery and one from 192 Ir. Nodal status, tumor size defined as T1, T2a (less than or equal to 3 cm), T2b (greater than 3 cm), and gingival extension were the only independent prognostic factors. The management of T1N0 and T2N0 SCC by 192 Ir to a dose of 65 or 70 Gy, using the Paris System, is recommended for lesions 3 cm or less and without gingival extension.     

Prognosis of epidermoid anal carcinoma regression after conservative treatment

The prospective study was concerned with definition of the clinical and therapeutic factors behind poor response of anal cancer to radio- (RT) or chemoradiotherapy (CRT). Out of 64 female and 8 male patients at the mean age of 57 (33-81), thirty six had split-course of 60-65 Gy (RT), twenty--60-65 Gy, 5-FU and mitomycin C (CRT) and eighteen--up to 55-65 Gy (1.5 Gy--session 1, 1.0 Gy--session 2) (hyper-fractionated RT) plus 5-FU, for squamous cell anal carcinoma. There was no endorectal ultrasound evidence of perirectal lymph node involvement (uN0): T1-2uN-M0 (n=46), T3-4uN0M0 (n=11), uN1 or N2-3 (groin or endorectal ultrasound: T1-2uN-M0 (n=46), T3-4uN0M0 (n=11), uN1 or N2-3 (groin metastases) were detected in 7 patients: T1-2uN1-2M0 (n=7), T3-4N1-3M0 (n=10). Endorectal ultrasound staging (ERUS) used a linear 7.5 MHz transducer. The uTNM system was devised on the basis of tumor invasion parameters. There were no tumors confined to the subendothelial layer of the anal canal (uT1); 24 (32.4%) tumors were confined to the internal anal sphincter (uT2); 19 (25.7%) invaded the external anal sphincter (uT3) and 31 (41.9%)--levator ani (uT4). All carcinomas T4 (n=9) corresponded to the uT4 category. Only T-stage and tumor invasion (uT) proved significant prognostic variables. Complete response of T1-2 was 79.2%, T3-4--33.3% (p=0.0003); uT2--95.8%, uT3--68.4%, and uT4--41.9% (except T4) (p=0.0001). In multivariate logistic analysis, uT alone appeared an independent variable (p=0.015). ERUS uTNM staging is more effective in prognosis for RT and CRT and, therefore, should be recommended for preliminary management of epidermoid anal carcinoma.     

Dose-volume analysis of radiotherapy for T1N0 invasive breast cancer treated by local excision and partial breast irradiation by low-dose-rate interstitial implant

PURPOSE: To evaluate the toxicity of partial breast irradiation (RT) using escalating doses of low-dose-rate interstitial implant as the sole adjuvant local therapy for selected T1N0 breast cancer patients treated by wide local excision. The results of a European Organization for Research and Treatment of Cancer study have demonstrated a significant local control benefit using external beam RT to 65 Gy compared with 50 Gy. Thus, the tolerance of escalating doses of partial breast RT should be determined, because this approach may become a standard treatment for patients with early-stage breast cancer. METHODS AND MATERIALS: Between 1997 and 2001, 48 patients with T1N0M0 breast cancer were enrolled into an institutional review board-approved Phase I/II protocol using low-dose-rate brachytherapy implants after wide local excision and lymph node staging surgery. Brachytherapy was started 3-4 days after surgery at a dose rate of 50 cGy/h, using (192)Ir sources evenly spaced to cover 3 cm around the resection margins. Typically, 2-3 planes were used, with a median of 14 catheters (range 10-16). The total dose was escalated in three groups: 50 Gy (n = 19), 55 Gy (n = 16), and 60 Gy (n = 13). The implant volume was calculated and used to classify patients into quartiles: 76-127 cm(3) (n = 12), 128-164 cm(3) (n = 12), 165-204 cm(3) (n = 12), and >204 cm(3) (n = 12). Cosmesis, patient satisfaction, treatment-related complications, mammographic abnormalities, rebiopsies, and disease status were recorded at each scheduled patient visit. RESULTS: The median follow-up for all patients was 23.1 months (range 2-43). Very good to excellent cosmetic results were observed in 91.8% of patients. Ninety-two percent of patients were satisfied with their cosmetic outcome and said they would choose brachytherapy again over the standard course of external beam RT. Six perioperative complications occurred: two developed bleeding at the time of catheter removal, two had abscesses, one developed a hematoma, and one had a nonhealing sinus tract requiring surgical intervention. Significant fibrosis (moderate-to-severe scarring and thickening of the skin and breast) was noted in only 4 patients; 1 had received 55 Gy and 3 had received 60 Gy. Abnormal posttreatment mammograms were seen in 19 patients. Eight patients underwent rebiopsy for abnormalities found either by mammography or on physical examination; all proved to be fat necrosis or post-RT changes. The rebiopsy rates appeared to correlate with doses >/=55 Gy (6 [75%] of 8 compared with 29 [60%]of 48 overall) and implant volumes >/=128 cm(3) (7 [87.5%] of 8 compared with 36 [75%] of 48 overall). To date, no local, regional, or distant recurrences have been observed. CONCLUSION: Low-dose-rate implants up to 60 Gy were well-tolerated overall. With an implant dose of 60 Gy, the incidence of posttreatment fibrosis (25%) appeared to be increased. Only the long-term follow-up of this and other implant studies will allow an understanding of the total radiation dose necessary for tumor control and the volume of breast that requires treatment.     

Long-term control of T2-T3 rectal adenocarcinoma with radiotherapy alone

PURPOSE: To analyze the long-term result of patients presenting with T2-T3 rectal adenocarcinoma treated with curative intent by radiotherapy (RT) alone, using a combination of contact RT, external beam RT, and brachytherapy with an iridium implant. Patients were considered unsuitable for surgery because of the presence of severe comorbidity or because they did not consent to surgery and the possibility of a permanent stoma. METHODS AND MATERIALS: Between 1986 and 1998, 63 patients (56 staged with endorectal ultrasonography) were entered into a pilot study. Patients had to have T2-T3, N0-N1, M0 adenocarcinoma of the middle or lower rectum involving less than two-thirds of the circumference. RT began with contact X-rays (80 Gy in 3 fractions for 21 days), followed by external beam RT (39 Gy in 13 fractions for 17 days) with a concomitant boost (4 Gy in 4 fractions). After a 4-6-week interval, an iridium implant delivered a completion dose of 20 Gy to the tumor. No chemotherapy was given. RESULTS: The median age of the patients was 72 years. Of the 63 patients, 41 had T2 and 22 had T3 tumors. The mean distance of the tumor from the anal verge was 3.6 cm. All patients completed treatment according to the protocol, except for 7 for whom brachytherapy was not performed. With a median follow-up time of 54 months, the primary local tumor control rate was 63%; after salvage surgery, the ultimate pelvic control was 73% (46 of 63). The 5-year overall survival rate was 64.4%, and for 42 patients aged <80 years, it was 78% with 10 patients alive and well at > or =10 years. No severe Grade 3-4 toxicity was seen. Acute proctitis was seen in most patients but did not require treatment interruption. Late rectal bleeding occurred in 24 patients. Only 1 required blood transfusion. Good anorectal function was maintained in 92% of living patients. The T stage was a strong prognostic factor, with a 5-year overall survival rate of 84% and 53% for T2 and T3 lesions, respectively, in patients <80 years old. CONCLUSION: This is the first report of long-term local control and survival for ultrasound-staged T2-T3 rectal adenocarcinoma treated by RT alone, showing that high-dose irradiation to a small volume can provide a high therapeutic ratio for such tumors.     

Limited external beam and interstitial 192iridium irradiation in the treatment of carcinoma of the base of the tongue: a ten year experience

A total of 70 patients with histologically proven diagnosis of carcinoma of the base of the tongue were treated with primary irradiation between May 1974 through April 1984. Fifty-eight (83%) of these patients had locally advanced tumors (Stage T3, T4, N2, N3). Fifty-one of the 70 (73%) patients had clinically palpable neck nodes at first presentation. All patients received a combination of external and interstitial irradiation. The dose of external irradiation was limited to 45-50 Gy over 4 1/2-5 1/2 weeks. Interstitial volume implants were performed 2-3 weeks after completion of external irradiation. The primary site as well as the vallecula, epsilateral pharyngeal wall, glossopalatine sulcus, tonsillar bed, and pillars were routinely implanted to encompass contiguous spread of the disease. The doses of implant varied according to the stage of disease, that is, 2000-2500 cGy for T1 and T2 lesions, 3000-4000 cGy for T3 and T4 lesions, with typical dose rates of 50-60 cGy per hour. The neck nodes were also separately implanted to deliver additional doses of 2000-4000 cGy in 50-80 hours. Overall, local tumor control was observed in 58 of 70 (83%) patients at minimum follow-up of 2 years. An absolute 3-year disease-free survival of the entire group was 67.0%. Treatment related complications such as soft tissue necrosis and/or osteoradionecrosis occurred in 8 of the 70 (11.4%) patients. The salvage of neck failures and the local failures was feasible in 74% and 46% of the patients, respectively either by surgery or by re-irradiation using interstitial 192iridium implant alone. This treatment region is well tolerated and it preserves the functional and asthetic integrity in most patients.     

Advanced head and neck carcinoma in women: treatment outcomes may not improve with accelerated hyperfractionated radiotherapy.

BACKGROUND: The authors undertook a retrospective study on local tumor control, survival, and complications of conventional irradiation compared with accelerated hyperfractionated irradiation in women with selected head and neck tumor sites. METHODS: One hundred eight consecutive women who were treated with radiation alone for cure during 1974-1998 were analyzed. Patients were excluded who had T1 tumors of the vocal cord and those who were treated with brachytherapy implants. Fifty-nine patients were treated with conventional fractionation once daily (QD) during 1974-1998 with a median dose of 2.1 grays (Gy) per fraction up to a total median dose of 69 Gy in a median overall time of 54 days. Forty-nine patients were treated with accelerated hyperfractionation twice daily (BID) during 1987-1998 at a median dose of 1.6 Gy per fraction BID, with an interfraction interval of 4-6 hours, for a total median dose of 66 Gy in 35 days. Patients were not randomized into the QD group or the BID group. RESULTS: The 7-year actuarial local control (LC) rates for T1-T2 tumors in QD-treated and BID-treated patients were 79% and 87%, respectively (P = not significant [NS]). For T3-T4 tumors, the LC rates at 7 years were 59% and 56% for the QD and BID groups, respectively (P = NS). A Cox regression analysis for LC showed that the significant variables were T classification and overall time. Schedule (QD or BID), total dose, dose per fraction, and patient age were not significant variables. For the QD and BID groups, the 7-year actuarial cause specific survival rates for patients with Stage I-II disease were 100% and 65%, respectively (P = 0.004), and, for patients with Stages III-IVA,IVB disease, the rates were 39% and 56%, respectively (P = NS), respectively. Acute morbidity was higher with the BID schedule: In the BID group, 8% of patients required tube or parenteral feeding, and 0% of patients in the QD group required such feeding (P = 0.04). The 5-year actuarial probability of Grade 3-5 late effects (according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer grading system) was 4% for the BID group and 0% for the QD group (P = NS). CONCLUSIONS: This study suggests that accelerated hyperfractionated irradiation for women with advanced carcinoma of the head and neck does not provide significantly better local tumor control or cause specific disease free survival compared with conventional fractionation. Women with these malignancies appear to have a better prognosis compared with men.     

Concurrent chemoradiotherapy with S-1 for T2N0 glottic carcinoma

Early glottic carcinoma has a good prognosis compared to other head and neck carcinomas, but we must aim for larynx preservation in the treatment. Regarding T1N0, larynx preservation rates are favorable even with radiotherapy alone. However for T2N0, the treatment strategies differ in each institution, and larynx preservation rates range from 72% to 85%, and are not high enough. We conducted a study to determine the efficacy of the concurrent chemoradiotherapy with S-1 for T2N0 glottic carcinoma. In this study, 12 patients with T2N0 glottic type laryngeal squamous cell carcinoma enrolled from the year 2004 to 2006, received one reduction dose of S-1 (80 or 100 mg/day) with concomitant irradiation with a total dose of 60-70 Gy (2.0 Gy/fr). The 2-week administration of S-1 followed by one-week rest was repeated during irradiation. In terms of adverse events of Grade 3 and above, Grade 3 mucositis and dermatitis were found in 2 patients each, but there was no cancellation nor interruption of S-1 or irradiation. All patients achieved pathological CR at the time of evaluation after the primary treatment, and no recurrences have been seen yet in any of the primary sites. Concurrent chemoradiotherapy with S-1 showed efficacy in T2N0 glottis carcinoma. Further investigation of this treatment with long-term follow up results is warranted.     

Interstitial radiation therapy for squamous cell carcinoma of the tonsillar region: the Creteil experience (1971-1981)

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.     

Squamous cell carcinoma of the anal canal

PURPOSE: To report the results of primary radiotherapy for treatment of anal canal carcinoma from the University of Florida series and review issues related to treatment of this disease. METHODS AND MATERIALS: Forty-nine patients were treated with primary radiation therapy (RT) for cure. Patients had a minimum 2-year follow-up (median, 9.8 years). After 1990, patients with lesions of at least 3 cm also received chemotherapy with fluorouracil (1000 mg/m(2)) plus cisplatin (100 mg/m(2)) or mitomycin (10-15 mg/m(2)) if medically fit (n = 26). RT was delivered with a 4-field box technique to deliver 45 Gy in 25 fractions. The inguinal nodes were treated daily using electrons to supplement the dose in that region to a total dose of 45 Gy if clinically negative or about 60 Gy if involved. There were no planned breaks. A 10- to 15-Gy boost was delivered using interstitial iridium 192 implant (n = 32), en face (60)Co field (n = 5), or external-beam photon fields (n = 11). RESULTS: Local control rates at 5 years were 100% for T1N0, 92% for T2N0 or N1, 75% for T3N0, 67% for T4N0, 88% for T4N(pos) or T(any)N2-3, and 85% overall. With surgical salvage, ultimate local control rates were 100%, 100%, 81%, 100%, and 88%, respectively, with 92% overall. Cause-specific survival rates at 5 years were 100% for Stage I, 88% for Stage II, 100% for Stage IIIA, and 70% for Stage IIIB. Absolute survival rates at 5 years were 62%, 68%, 100%, and 70%. Sphincter preservation rates were 83%, 79%, 75%, and 100% by stage and 81% overall. There was an improvement in local control with the addition of chemotherapy in more advanced disease, but it was not significant. There was an increase in acute toxicity with the addition of chemotherapy (12% > or = Grade 4) but not long-term toxicity. Late toxicity requiring colostomy occurred in 6% of patients and consisted of soft tissue necrosis. CONCLUSIONS: The majority of patients with anal canal carcinoma can be treated with curative intent using a sphincter-sparing approach of radiation with or without chemotherapy even with advanced disease. With the addition of chemotherapy to radiation, there is an increased risk of acute toxicity and about 1-2% incidence of toxic death. Smaller tumors (T1 and early T2) probably do not require the addition of chemotherapy.     

Carcinoma of the tonsillar fossa: prognostic factors and long-term therapy outcome

Purpose: To identify prognostic parameters and evaluate the therapeutic outcomes for patients with carcinoma of the tonsillar fossa treated with three treatment modalities.

Methods and Materials: The results of therapy are reported in 384 patients with histologically proven epidermoid carcinoma of the tonsillar fossa; 154 were treated with irradiation alone (55–70 Gy), 144 with preoperative radiation therapy (20–40 Gy), and 86 with postoperative irradiation (50–60 Gy). The operation in all but four patients in the last two groups consisted of an en bloc radical tonsillectomy with ipsilateral lymph node dissection.

Results: Treatment modality and total irradiation doses had no impact on survival. Actuarial 10-year disease-free survival rates were 65% for patients with T1 tumors, 60% for T2, 60% for T3, and 30% for T4 disease. Patients with no cervical lymphadenopathy or with a small metastatic lymph node (N1) had better disease-free survival (60% and 70%, respectively) at 5 years than those with large or fixed lymph nodes (30%). Primary tumor recurrence (local, marginal) rates in the T1, T2, and T3 groups were 20–25% in patients treated with irradiation and surgery and 31% for those treated with irradiation alone (difference not statistically significant). In patients with T4 disease treated with surgery and postoperative irradiation, the local failure rate was 32% compared with 86% with low-dose preoperative irradiation and 47% with irradiation alone (p = 0.03). The overall recurrence rates in the neck were 10% for N0 patients, 25% for N1 and N2, and 35–40% for patients with N3 cervical lymph nodes, without significant differences among the various treatment groups. The incidence of contralateral neck recurrences was 8% with the various treatment modalities. On multivariate analysis the only significant factors for local tumor control and disease-free survival were T and N stage (p = 0.04–0.001). Fatal complications were noted in 7 of 144 (5%) patients treated with preoperative irradiation and surgery, 2 of 86 (2%) of those receiving postoperative irradiation, and 2 of 154 (1.3%) patients treated with radiation therapy alone. Other moderate or severe nonfatal sequelae were noted in 30% of the patients treated with preoperative irradiation and surgery, in 53% treated with postoperative irradiation, and in 19% receiving radiation therapy alone.

Conclusion: Primary tumor and neck node stage are the only significant prognostic factors influencing locoregional tumor control and disease-free survival. Treatment modality had no significant impact on outcome. Radiation therapy remains the treatment of choice for patients with stage T1–T2 carcinoma of the tonsillar fossa. In patients with T3–T4 tumors and good general condition, combination surgery and postoperative irradiation offers better tumor control than single-modality and preoperative irradiation procedures, but with greater morbidity.     

Primary radiotherapy in the treatment of stage I and II oral tongue cancers: importance of the proportion of therapy delivered with interstitial therapy

From January 1963 through December 1979, 103 patients with Stage T1N0 and T2N0 squamous cell carcinomas of the oral tongue were treated with definitive radiotherapy. The primary was Stage T1 in 18 patients and T2 in 85 patients. Therapy to the primary consisted of interstitial therapy only in 18 patients, 16-37 Gy in 2.4-4.0 Gy fractions followed by interstitial therapy to doses of 38-55 Gy in 31 patients, external therapy of 40-50 Gy with interstitial therapy of 20-40 Gy in 46 patients, and external beam only to doses of 45-82 Gy in 8 patients. Follow-up ranged from 2 to 290 months (median 159 months). Five of the 8 patients treated with external therapy alone and 6 of the 18 patients treated with interstitial therapy failed at the primary site. In those patients treated with a combination of external and interstitial therapy the 2-year local control rate was 92% for patients treated with external therapy to doses of less than 40 Gy combined with a moderately high dose of brachytherapy, compared with 65% for patients who received external therapy to doses of greater than or equal to 40 Gy with lower brachytherapy doses (p = .01). Conversely the risk of failure in the neck was directly related to the dose delivered by external beam therapy. In field recurrence occurred in 44% of patients receiving no therapy to the neck. 27% in those receiving less than 40 Gy, and 11% in those patients with neck treatment to greater than or equal to 40 Gy. Eleven of 87 (13%) of patients who were at risk for complications for greater than or equal to 24 months developed severe complications; severe complications were more likely to occur in the group who received most of their therapy with external beam irradiation. These data show that a high dose of interstitial therapy is necessary to secure optimum local control of early primary tongue cancer. Because of the high frequency of moderate to severe late complications in this series we have adopted a policy of initial surgery for most oral tongue cancers with postoperative radiotherapy if indicated by pathological features predictive of a high rate of local-regional failure.     

Prognostic implications of downstaging following preoperative radiation therapy for operable T3–T4 rectal cancer

Purpose: To evaluate the prognostic value of tumor downstaging after preoperative radiation for resectable rectal cancer.

Methods and Materials: Eighty-eight patients with non-metastatic resectable rectal cancers (76 T3 and 12 T4) were treated with preoperative irradiation. Median dose was 40 Gy (30–46 Gy) delivered over 32 days (range 11–40). Seventeen patients received preoperative chemotherapy, two courses of 5-fluorouracil (5FU) 350 mg/m²/day and folinic acid 20 mg/m²/day; 5 days per week during the first and fifth weeks of radiotherapy. Surgery was performed with a mean delay of 46 days after completion of irradiation and included 66 abdominoperineal resections and 22 anal sphincter-preserving procedures. Postoperative chemotherapy was administered in 44 patients.

Results: Histological tumor stages were: complete histological response in 7%, pT2N0 in 19%, pT3N0 in 46%, and pT2-3N1 in 28%. Tumor downstaging occurred in 26%. No predictive factor of downstaging was statistically significant. The median follow-up was 33 months. The 3- and 5-year cancer-specific survival rates were 100% for the pT0N0 and pT2N0, respectively, 89% and 68% for pT3N0, and 64% and 0% for pT2T3N1. After preoperative irradiation, the pathological tumor stages remained a prognostic factor. Patients with downstaging (pT0T2N0) had significantly higher cancer-specific survival rates than the group without downstaging: 100% and 80% at 3 years, and 100% and 45% at 5 years; respectively (p = 0.011). The 3- and 5-year recurrence free-survival rates were 94% for the group with downstaging and 56% and 50%, respectively, for the group without downstaging (p = 0.002).

Conclusion: Downstaging after preoperative irradiation in this retrospective study results in an improvement in local control and survival.     

Iridium-192 interstitial therapy for squamous cell carcinoma of the penis.

From February 1971 through February 1989, 51 patients with biopsy proven epidermoid carcinoma of the penis were treated with interstitial therapy (Iridium 192). The breakdown according to the stage was T1s = 3, T1 = 14, T2 = 28, T3 = 6, N0 = 43, N1 = 7, N2 = 1. The dose ranged from 50 to 65 Gy (mean: 60 Gy). Patients without clinical nodal involvement received no treatment to the nodes. Stage N1 and N2 patients had surgery and external irradiation to the inguinal and iliac nodes. Six of fifty-one (12%) patients developed nodal and/or metastatic disease following therapy. Five of six presented initially with clinical nodal involvement. Seven of fifty-one (14%) developed local recurrence only, requiring surgery (four partial penectomies, three total penectomies). Six of these seven patients are alive and free of disease with a mean follow-up of 5.5 years. Nine of thirty eight (23%) patients with local control developed local necrosis. The treatment consisted of local excision (one patient), partial amputation (six patients) or total amputation (two patients). Partial urethral stenosis was noted in 17/38 (45%) of the patients. Foreskin sclerosis occurred in 3/38 (8%) uncircumcised patients. Interstitial irradiation for penile carcinoma provided effective local control rates, especially for T1-T2 patients (91%). Local failures could be treated successfully with surgery. Complications could be treated conservatively in most patients. Local control with penile conservation was achieved in 67% of all patients and 75% of patients with T1-T2 disease.     

Iridium-192 brachytherapy in the management of 147 T2N0 oral tongue carcinomas treated with irradiation alone: comparison of two treatment techniques.

Our purpose is to analyse local control, complications relative to the proportion of total dose delivered by external beam irradiation versus interstitial implant in 147 patients with previously untreated T2N0 squamous cell carcinoma of the oral tongue, managed between 1973 and 1986 (UICC staging system). These T2N0 patients are part of a larger group of 430 patients with oral tongue carcinoma (T1, T2, T3) treated with irradiation alone. Of these 147 T2N0 patients, 70 were treated with interstitial implant alone and 77 with both external beam irradiation and implant. In the group treated with interstitial implant alone, the 5-year local control was 89.8% against 50.6% in those treated with external beam irradiation and interstitial implant (log-rank test, p = 0.00002); 67.6% versus 46.5% for locoregional control (p = 0.029); and 62.2% versus 34.7% for specific survival (p = 0.0015). Since 1980, all the patients treated by iridium implantation were protected with a leaded spacing device between the tongue and the mandible. Soft tissue necrosis and bone exposure following treatment were scored according to the following criteria: minor, moderate or severe. Seven moderate and one severe complications were recorded in the brachytherapy group. None of the patients required surgery. In the combined treatment group, six moderate and two severe complications were observed. Patients treated with interstitial implant alone, and showing moderate or severe complications had received an average brachytherapy dose of 7600 cGy. In the same group, the patients without complications had received an average dose of 6800 cGy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulsed dose rate brachytherapy in head and neck cancers. Feasibility study of a French cooperative group.

PURPOSE: To prospectively evaluate the feasibility of pulsed dose rate (PDR) brachytherapy to mimic the continuous low dose rate (cLDR) iridium wire technique in head and neck carcinomas. MATERIALS AND METHODS: A series of 30 patients were included from June 1995 to May 1998. The primaries were located in the oral cavity (four T1, seven T2 and two T3), the velotonsillar arch (eight T1 and eight T2) and the posterior wall (one T3). Thirteen were irradiated by exclusive brachytherapy (dose, > or =45 Gy). The PDR delivered 0.5 Gy/pulse, one pulse/h, day and night, to mimic cLDR irradiation. RESULTS: The implantation was feasible for all the patients, usually easy and of good quality. The mean duration/pulse was 13 min, with a mean source activity of 171 mCi. Patient tolerance was poor in nine cases. Sixteen patients could receive the whole PDR treatment with a total ranging from 30 to 120 pulses without any problem. Seven had short breakdowns (< or =6 h). Seven had definitive breakdowns, but could end the irradiation by manual afterloading of iridium 192 wires. The radioprotection was better (or complete), except for one patient. Most of the breakdowns were related to kinking or flattering of the tube. CONCLUSIONS: PDR is feasible in head and neck carcinomas, but necessitates improvement of the quality and control of the plastic tubes.     

Twice-a-day radiotherapy for head and neck cancer: the Catalan Institute of Oncology experience.

PURPOSE: The purpose of this work is to evaluate the contribution of hyperfractionated radiotherapy (RT) in head and neck cancer by sub-localisation. PATIENTS AND METHODS: From 1992 to 1999, 318 patients with squamous head and neck tumours treated by hyperfraction RT were analysed according to their sub-localisation and stage. Fractions used were 1.2 Gy twice-a-day with a curative intent on all patients, to a total mean dose of 79.14 Gy. Treatment protocols by localisation were: larynx: 55 patients with T2N0 and T1-2N1 tumours treated with only RT and 27 patients with T3N0-1 in complete remission after three cycles of induction chemotherapy (ICT); hypopharynx: 29 patients with T2-4N0-2b resectable tumors in response to three cycles of ICT; oropharynx: 48 patients with T2-3N0-1 and T1N1 tumours treated with only RT; 34 patients with nasopharynx tumours treated with RT and three cycles of ICT if T4 or >N1; finally, 125 patients with non-surgical tumours of any localisation treated with four cycles of induction CT and RT. RESULTS: LARYNX: Actuarial local control (LC), disease-free survival (DFS) and overall survival (OS) at 5 years were 78, 73 and 48%, respectively, in T2 tumours and 75, 72 and 60% in stage III disease. HYPOPHARYNX: Actuarial LC, DFS and OS at 4 years were 44, 39 and 35%, respectively. OROPHARYNX: Actuarial LC, DFS and OS at 5 years were 52, 44 and 31%, respectively. NASOPHARYNX: Actuarial LC, DFS and OS at 5 years were 78, 72 and 78%, respectively. NON-SURGICAL TUMORS: Actuarial LC, DFS and OS at 5 years were 39, 33 and 19%, respectively. A total of 47 patients (14.8%) of the overall group had a second tumour, 72% of them tobacco-related. Only patients with nasopharynx tumours had a low incidence of second tumours. CONCLUSIONS: Twice-a-day external RT can be effectively managed in patients with head and neck cancer. Second neoplasm and intercurrent diseases become an important problem in low and medium stages whereas disease recurrences is the main problem in advanced stages. Results by localisation permit to obtain conclusions about their indications in each one.