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.     

Hyperfractionation for head and neck cancer

Between March 1978 and April 1984, 144 patients with 148 moderately advanced to advanced primary squamous cell carcinomas of the head and neck received treatment with curative intent with twice-a-day irradiation (120 cGy/fraction, 4-6 hour interfraction interval). Eighty-eight percent of the patients had AJCC Stage III-IV cancers. One hundred and thirty-two patients received irradiation alone to the primary site with or without radical neck dissection, with surgery reserved for salvage. The total doses administered were 7440-7920 cGy in the majority of instances. In 19 patients with oropharyngeal lesions, a 1000-1500 cGy radium needle boost was added after the basic dose. Twelve patients received preoperative irradiation (5040-6000 cGy) followed by primary resection and radical neck dissection. Local control results following irradiation alone to total doses of greater than 7000 cGy with minimum 2-year follow-up were 25/31 (81%), 38/50 (76%), and 5/25 (20%) for T2, T3, and T4 cancers, respectively. Local control rates did not correlate well with total dose. Local control following preoperative irradiation plus primary resection was obtained in 4 of 5 T3 and 2 of 3 T4 primary lesions. The 5-year actuarial rates of neck control were 100% for N0 (45 patients), 90% for N1 (25 patients), 77% for N2 (23 patients), 50% for N3A (9 patients), and 70% for N3B (42 patients). The 5-year actuarial rates of continuous disease control above the clavicles were 73% for Stage III, 64% for Stage IVA, and 32% for Stage IVB. The actuarial 4-year rate of continuous disease control above the clavicles was 78% for Stage II. For patients whose disease was controlled above the clavicles, distant metastases developed in 4% of patients with Stage II-III disease and in 18% of patients with Stage IV disease. Radiation complications following irradiation alone to the primary site correlated with total dose. Complications of planned neck dissection(s) were acceptable. Complications of salvage surgery at the primary site were similar to those seen in patients treated once a day. The actuarial 5-year survival rates, according to modified AJCC stage, were 59% for Stage III, 37% for Stage IVA, and 23% for Stage IVB. The actuarial 4-year survival rate for Stage II was 69%. Compared to historical control groups treated with once-a-day, continuous-course irradiation at our institution, twice-a-day treatment has produced local control results that are higher by 10-15 percentage points.     

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.     

Radiation treatment of lateral epilaryngeal cancer. Prognostic factors and results

Treatment results of epilaryngeal cancer are rarely individualized in the world literature. For this purpose, we have reviewed the records of 167 patients with squamous cell carcinoma of the lateral epilarynx who received radical radiotherapy at the Institut Curie on a megavoltage unit, between 1959-1975. Two-thirds of the lesions were located at the junction of the ary- and pharyngo-epiglottic folds and lateral border of the epiglottis. Forty-four percent of patients had advanced primary lesions (T3, T4) and over 50% had palpable neck nodes at the time of presentation. The absolute survival for the entire patient population at 3 and 5 years was 44% and 32%. Local control for T1 and T2 tumors at 3 years was about 80%. Survival at 5 years for the N0 Stage patient was 40%, whereas it was about 20% for those with clinically palpable nodes. Patients with exophytic tumors and lesions which regressed completely within 8 weeks following irradiation had a significantly better 3-year survival and local control than those with nonexophytic tumors and with tumors which had incompletely regressed after irradiation. Radiotherapy remains the treatment of choice for the small tumors (T1, T2) but the association of radical surgery with pre- or postoperative radiotherapy should be considered for advanced disease.     

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.     

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.     

Carcinoma of the nasopharynx: factors affecting prognosis.

This is a retrospective analysis of 143 patients with histologically confirmed epidermoid carcinoma of the nasopharynx treated with definitive irradiation. Patients were treated with a combination of Cobalt-60, 4 to 6 MV X rays, and 18 to 25 MV X rays to the primary tumor and the upper necks, excluding the spinal cord at 4000 to 4500 cGy to total doses of 6000 to 7000 cGy. At 10 years the actuarial primary tumor failure rate was 15% in T1, 25% in T2, 33% in T3, and 60% in T4 lesions. The corresponding failure rate in the neck was 18% for N0, 14% for N1, and 33% for N2 and N3 lymphadenopathy. The incidence of distant metastasis was related to the stage of the cervical lymphadenopathy: 16% in patients with N0-N1 nodes compared with 40% in the N2-3 node group. The actuarial 10-year disease-free survival rate was 55% to 60% for T1-3N0-1 tumors, 45% for T1-3N2-3 tumors, 35% for T4N0-1, and 20% for T4N2-3 lesions. The overall 10-year survival rate was about 40% for patients with T1-2N0-1 tumors, 30% for those with T3 any N stage tumors, and only 10% for the patients with T4 lesions. Multivariate analysis showed that tumor stage and histological type, cranial nerve involvement, patient age, and doses of irradiation to the nasopharynx were significant prognostic factors for local/regional tumor control. Increasing doses of irradiation resulted in nasopharynx tumor control in 80% of the patients receiving 6600 to 7000 cGy and 100% of those receiving over 7000 cGy in the T1, T2, and T3 tumors. However, the tumor control rate did not rise above 55% even for doses over 7000 cGy in the T4 lesions. Local tumor control was higher in patients who had simulation (55/78 = 71%) compared with those on whom simulation was not performed (34/61 = 56%) (p = 0.10). Moreover, patients with more than 75% of the reviewed films judged as adequate had 69% primary tumor control (66/96) compared with 53% (23/43) for those with fewer than 75% adequate portal films (p = 0.07).     

Local-regional non-rhabdomyosarcomatous soft tissue sarcomas of the head and neck

Between 1962 and 1987, 112 consecutive patients were treated at St. Jude Children's Research Hospital for soft tissue sarcomas of the head and neck region; 18 of these children (16%) had histologic subtypes other than rhabdomyosarcoma. We evaluated the impact of surgery, postoperative chemotherapy, and irradiation on local control and survival in these cases. Three patients who had complete resection of tumors and received no further treatment are alive without disease at 36, 42, and 162 months. Local control was achieved in 1 of 2 patients with microscopic residual tumor and 4 of 9 patients with gross residual tumor who were treated with irradiation (2500-5040 cGy). Chemotherapy was the only postoperative treatment in three patients; only one achieved lasting local control. One patient was treated with irradiation only; his primary site showed no tumor cells at autopsy following an automobile accident. Overall, local control was achieved in 50% of patients; the disease-free survival rate at 3 years was 44%. The prognosis for patients with nonresectable tumors remains unsatisfactory because of the difficulty in securing local control. A revised therapeutic approach to these patients is presented.     

Postoperative radiation therapy for major salivary gland malignancies

Between 1966 and 1982 there have been 46 patients treated with surgery plus post-operative radiation therapy for malignant tumors of salivary gland origin. The indication(s) for radiotherapy included positive margins (42%), advanced local tumor (37%), positive nodes (33%), or high grade histology (48%). Overall actuarial local control at 5 years was 73%, being 100% for T1, 83% for T2, 80% for T3, and 43% for T4. Actuarial survival at 5 years was 80% for T1, 83% for T2, 60% for T3, and 48% for T4. Patients with positive nodes (N+) did worse than those with negative nodes (No), with locoregional control and survival at 5 years being 58% vs. 83%, (P = 0.025) and 38% vs. 80% (P = less than .01), respectively. We found no need for contralateral neck treatment even for those with positive nodes. Also, to date, none of eight patients with adenoid cystic histology has failed locally, as opposed to three of eight failures in patients treated with surgery alone. We believe that post-operative irradiation provides excellent locoregional control for appropriate patients with malignant tumors of major salivary glands.     

Breast conservation in the treatment of early breast cancer. A 20-year follow-up

Two hundred sixty-three patients with unilateral primary breast cancer, treated by local excision of the primary tumor and radical radiation therapy between 1954 and 1969, were followed up for a minimum of 10 years and a maximum of 20 years. The treatment plan delivered 4500 rad in fractions of orthovoltage irradiation to five fields: tangential breast fields, axilla with posterior axillary field, parasternal and supraclavicular, with a subsequent boost of 1000 rad to the primary tumor site, axilla, and supraclavicular fossa. Patients were clinically staged using the TNM (UICC) system; 115 patients had tumors less than 2 cm in diameter and a clinically negative axilla (T1N0N1a), 96 had tumors 2 to 5 cm in diameter with a clinically negative axilla (T2N0N1a), and 52 had tumors less than 5 cm in diameter and clinical axillary lymph node metastases (T1T2N1b). The actuarial relapse-free survival of patients with T1N0N1a tumors was 72% at 5 years, 59% at 10 years, and 47% at both 15 and 20 years. The relapse-free survival of patients with T2N0N1a tumors was not statistically different (P greater than 0.05). A significantly worse survival was observed in patients with clinical axillary lymph node metastases (T1T2N1b), with a survival of 37% at 5 years, 29% at 10 years, 23% at 15 years, and 22% at 20 years, when compared with patients with clinically negative lymph nodes (P less than 0.01). Locoregional relapse occurred in 22%, at 10 years, of those patients with T1 or T2N0N1a tumors and 52% of the patients with T1T2N1b tumors. The pattern of locoregional relapses indicated that approximately 50% occur at least 5 years after treatment; this contrasts with the pattern of early locoregional relapse after mastectomy. The commonest sites of relapse were in the breast in 19% and axilla in 6% of patients with T1 or T2N0N1a tumors. There was no attenuation of the radiation dose administered at the site of a subsequent relapse. Surgery for radiation failure produced a 42% crude relapse-free survival at 5 years after salvage mastectomy in those patients originally treated for T1 or T1N0N1a tumors. The results of this study suggest that a significant proportion of patients relapse locally over a prolonged period after breast conservation. The evolution of new radiation techniques may provide better locoregional control and early salvage surgery may result in improved long-term survival.     

Tumor excision and radiotherapy as primary treatment of breast cancer. Analysis of patient and treatment parameters and local control

From 1966 to 1979, 235 patients with operable breast cancer were treated by tumor excision and radiotherapy. The actuarial survival at 10 years was 94.8% for stage I and 58% for stage II tumors. Local recurrent cancer was seen in 23/235 patients and was related to T stage, N stage, width of surgical excision, radiation dose to the tumor bed and anatomopathological differentiation. Recurrences were seen in 1/7 of T0, 3/57 (5.2%) of T1, 11/102 (10.8%) of T2 and 2/6 of T3 tumors. Local control in the breast decreased significantly in N1b cases (p = 0.005) or when 3 or more axillary lymph nodes were positive (p = 0.0074). Local control after segmentectomy or tumorectomy was identical. However, a poorer local control was found in 20 cases treated with subtotal resection (p less than 0.05). A clear dose-local control relationship was found in this material, with a 100% local control in all T0, T1 tumors which received more than 1800 ret and all T2 tumors which received more than 2000 ret. As 19 of 23 breast recurrences were seen at the primary site in the breast we believe that booster doses should be given in order to maximise local control.     

A retrospective study of three treatment techniques for T1-T2 base of tongue lesions: surgery plus postoperative radiation, external radiation plus interstitial implantation and external radiation alone

One hundred and ten patients with base of tongue tumors less than or equal to 4 cm in diameter (T1 and T2 by the UICC staging system) were treated according to three different methods; surgery followed by external radiation in 27 cases, external radiation followed by interstitial implantation in 29 cases, and external radiation alone in 54 cases. The median follow-up is 8 years with a minimum of 4 years. Local failure occurred twice as often in patients treated by external radiation alone (43%) compared to the other two therapeutic modalities (20.5% for external radiation plus implantation and 18.5% for surgery plus radiation). Ninety per cent of recurrences occurred within the first 2 years. The 5-year survival rate for N0 and N1 nodal disease is 30.5% for patients treated by external radiation alone and 50% for the other two methods. This survival difference is related to poorer local control. Surgery plus external radiation gives identical results to those of external radiation and interstitial implantation, but surgery is only practical for peripheral base of tongue tumors and it has poorer functional results. External radiation followed by interstitial implantation is, in our opinion, the best of the three therapeutic techniques for T1 and T2 base of tongue tumors.     

Carcinoma of the tonsil: the effect of dose-time-volume factors on local control

Between 1970 and 1979, 372 patients with squamous cell carcinoma of the tonsil were treated with primary irradiation therapy, with salvage surgery for failures. The median age was 60 years and the male to female ratio was 2:1. The staging system used was the 1974 UICC TNM system. There were 47 T1 lesions (13%), 161 T2 lesions (43%), and 164 T3 lesions (44%). Regional nodes were not palpable in 173 (46%); 122 had N1 nodes (33%), 6 had N2 nodes (2%) and 71 had N3 nodes (19%). All patients received external beam radiation which was supplemented in 68 patients with a radioactive implant for disease into adjacent tongue. The overall survival for all patients was 38% at 5 years and 54% when corrected for intercurrent disease. Local control was 87% for T1 lesions, 68% for T2 lesions and 50% for T3 lesions. Regional control was 96% for N0, 67% for N1 and 37% for N2-3. A detailed dose-time-volume analysis revealed that increasing volume improved local control in T1 and T2 lesions (77% had local control if the volume was greater than 80 cm2 versus 53% if the volume was less than 80 cm2, p = 0.014), except for T3 lesions. Increasing the dose in the range of 5000 to 6500 rad had no significant effect on primary control in any stage of disease. The addition of a radioactive implant did not increase local control if disease extended into the tongue (57% local control if implant, 52% if no implant). This study demonstrates the significance of adequate treatment volume in local control for carcinoma of the tonsil. No significant dose response was found and subsequent surgery was not compromised when a moderate dose of radiation was used.     

早期肛门癌的放射治疗

目的 分析早期肛门癌的放射治疗结果。方法 ２７例Ｔ１－２Ｎ０Ｍ０期肛门癌患者接受了单纯放射治疗，其中７例盆腔野加局部野，２０例局部野照射。结果 总的５年生存率为７９．１％，１８例患者保留了肛门功能。７例局部复发，１例腹肌麻巴结复发，５例经补救治疗后获控制。结论 早期肛门癌放射治疗可以达到与根治术相同的治愈率，能使大约２／３的患者保存肛门功能。     

Ewing’s sarcoma family tumors of the humerus: Outcome of patients treated with radiotherapy, surgery or surgery and adjuvant radiotherapy

Background and purpose

Local treatment for non-metastatic Ewing’s sarcoma family tumors (ESFTs) is controversial. Results achieved in a single institution in patients with ESFT of the humerus are presented.

Materials and methods

Patients treated between 1983 and 2000 for ESFT of the humerus were included. The impact of local treatment (surgery, radiotherapy or both) on outcome was assessed.

Results

55 patients: 34 males (62%); 21 females (38%); mean age: 17.9 (range: 3-40). Local treatment: surgery in 27 patients (49%), radiotherapy in 17 (31%) and surgery followed by radiotherapy in 11 (20%). After a mean follow-up of 15 years (range: 7-25 years), 27 patients (49%) remained continuously disease free, 27 (49%) relapsed and one died of chemotherapy toxicity. The local recurrence rate was 13% overall: 18% (3/17) after radiotherapy, 7% (2/27) after surgery and 19% (2/11) after surgery followed by adjuvant radiotherapy (p = ns). On the contrary, the 10-year EFS resulted significantly higher after surgery (64%) than radiotherapy (18%, p < 0.01). The 10-year EFS after surgery followed by radiotherapy was 45%, non-significantly different from EFS of surgery or radiotherapy alone. The 3 treatment groups had a similar distribution of the most important prognostic variables for ESFT, except for the tumor-bone ratio, which was higher for patients who underwent radiotherapy, and surgical margins, more frequently inadequate in patients treated with a combination of radiotherapy and surgery compared to those managed by surgery alone.

Conclusions

In conclusion this study shows that in EFST of the humerus surgery is the best treatment for small tumors. Large tumors are probably best treated with surgery too, as long as good functional results and quality of life can be expected, and adequate surgical margins are achievable. Postoperative radiotherapy is mandatory when margins are inadequate. A high local control rate, of more than 80%, can be obtained also by means of radiotherapy alone.     

Time-dose-response relationships in postoperatively irradiated patients with head and neck squamous cell carcinomas.

BACKGROUND AND PURPOSE: To define the influence of the dose and time on the response to treatment in postoperatively irradiated head and neck cancer patients and to establish a good prediction of failure. METHODS AND MATERIALS: From January 1985 to December 1995, 214 patients with histologically proven head and neck squamous cell carcinomas were irradiated after radical surgery or single tumour resection according to surgical and histopathological findings. The total doses given ranged between 50 and 75 Gy to the primary bed tumour and between 42 and 56 Gy to the neck with fraction sizes of 1.7-2 Gy/day. The median length of the time interval between surgery and radiotherapy, time of irradiation and total treatment time were 81, 59 and 139 days, respectively. The end-point analyzed was the local-regional tumour control rate at the primary tumour bed and neck for 5 years from the beginning of radiotherapy. Univariate and multivariate analyses were used to determine predictors of failure from among the following studied variables: (i), clinical stage (T/N) of the patients; (ii), tumour grade; (iii), neck surgery; (iv), tumour margins; (v), histological tumour nodal extension; (vi), chemotherapy; (vii), normalized total dose; (viii), time interval between surgery and radiotherapy; (ix), time of irradiation; and (x), total treatment time. RESULTS: The actuarial 5-year tumour control rate for the entire group was 72%, and 92% of the patients who achieved local control are currently alive without disease. Tumour control was inversely related to T stage (83% for T2 vs. 57% for T4) and the probability of local control within each stage was dependent on the N status (> or =71% for T3-T4/N0 vs. 31-44% for T3-T4/N1-N3). Histological N status and tumour margins, but not tumour grade, impacted significantly on tumour control. When local control was analyzed as a function of the dose to the primary, a non-significant negative dose-response relationship was found. The total treatment time was a significant prognostic factor, and the time interval between surgery and irradiation proved to be an independent predictor of failure. CONCLUSIONS: Despite the absence of a statistically significant dose-response relationship, the present results suggest that postoperative irradiation treatment given to patients with head and neck squamous cell carcinomas should not be unduly prolonged, in order to minimize the amount of tumour cell proliferation. In these patients, nodal involvement, positive margins of the resected specimens and time interval between surgery and irradiation were the most important prognostic factors.     

Postoperative brachytherapy alone for T1-2 N0 squamous cell carcinomas of the oral tongue and floor of mouth with close or positive margins

PURPOSE: To evaluate the efficacy of postoperative brachytherapy alone (brachy) for Stage T1-2 squamous cell carcinomas (SCC) of the floor of mouth (FM) and the oral tongue (OT) with close or positive margins. METHODS AND MATERIALS: Between 1979 and 1993, 36 patients with T1-2 N0 (24 T1, 12 T2) OT (19), and FOM (17) SCC with close or positive margins following surgery underwent postoperative brachy. Mean patient age was 56 years (range 37-81) and sex ratio was 3.5:1 male:female. Mean surgery to brachy interval was 36 days (range 16-68). The technique used was interstitial Iridium-192 ((192)Ir) brachytherapy with plastic tubes and manual afterloading. Mean total dose was 60 Gy (range 50-67.4) at a mean dose rate of 0.64 Gy/h (range 0.32-0.94). Mean patient follow-up was 80 months. RESULTS: The 5-year actuarial overall and cause-specific survivals of the entire group were 75% and 85%, respectively. The local control was 88.5% at 2 years, with a plateau apparent after 23 months. Of the 4 local relapses, 2 were salvaged with surgery and external beam radiotherapy (EBR). No tumor or treatment factors, including tumor size, margin status, disease site, or radiation dose, were correlated with local control. The 2 head and neck second primaries underwent curative treatment on nonirradiated tissue. One patient developed a grade 3 sequelae (bone and soft tissue necrosis). Grade 2-3 chronic sequelae were seen in 7 of 17 and 3 of 19 FOM and OT tumors, respectively (p = 0.09). CONCLUSION: Postoperative brachy is a promising approach in T1-2 N0 OT and FOM SCC with close or positive margins. This approach is associated with high rate of locoregional control and low risk of chronic sequelae, obviates major surgery, avoids potential sequelae of EBR (xerostomia, dysgueusia, fibrosis), and avoids treatment of second head and neck primary on nonirradiated tissues.     

Role of preoperative radiotherapy in preservation of the anal sphincter in cancer of the lower rectum

Short term preoperative irradiation of rectal cancer (30 Gy in 12 days) followed by a two-month rest before surgery has proven to be more efficient than most usual protocols of radiotherapy. In a series of 136 tumors T2, T3 or T4, tumor-free specimens and Duke'A lesions were found at surgery in 17% and 36% respectively. Surgeons took advantage of the tumor regression and performed sphincter-saving surgery in 41 patients with T2, T3 or T4 tumors of the lower third of the rectum. Of 30 patients followed from 2 to 6 years, the disease-free survival rate is 86%. Only one local failure was observed and subsequently controlled by abdomino-perineal resection.     

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.     

Stage I-II carcinoma of the anterior two-thirds of the tongue treated with different modalities: a retrospective analysis of 244 patients.

Treatment results of 244 patients with stage I-II cancer of the mobile tongue were analyzed according to the modalities employed (implantation, surgery, cryosurgery and intraoral irradiation). Overall local control rates at three years were 90 +/- 3% for implant, 89 +/- 7% for cryosurgery, and 84 +/- 9% for surgery. Local control rates in stage II patients treated with intraoral electron irradiation, however, were only 50 +/- 13%. Five-year survival rates were 72 +/- 3% with no significant differences observed in patients with either stage I or stage II regardless of treatment modality. Sixty percent (29/48) of the patients with local recurrences were salvaged by the second treatment. Since the local control and survival achieved by these modalities were similar, with the exception of patients with stage II treated by intraoral electron irradiation, we recommend interstitial implantation with iridium, intraoral electron irradiation or surgery for patients with T1 tumors, and iridium implantation or surgery for patients with T2 tumors. For those with superficial lesions measuring 5 mm or less in thickness, cryosurgery is being offered as an alternative. The patient can choose the treatment modality taking into account his/her age, sex and profession.