Postoperative radiation for cervical cancer with pathologic risk factors

PURPOSE: To examine the efficacy of postoperative radiation therapy for early-stage cervical cancer with pathologic risk factors. METHODS AND MATERIALS: We reviewed the charts of 83 patients who received postoperative radiation therapy at our facility from March 1980 to November 1993 for early stage cervix cancer with positive surgical margins, positive pelvic or periaortic lymph nodes, lymphovascular space invasion, deep invasion, or for disease discovered incidently at simple hysterectomy. Twenty-eight patients received low dose rate (LDR) intracavitary radiation with or without external beam pelvic irradiation and 55 patients received external beam pelvic irradiation with high dose rate (HDR) intracavitary implants. Of these 83 patients, 66 were evaluable--20 LDR and 46 HDR patients. All patients received 45-50 Gy external beam irradiation and 20 Gy LDR equivalent intracavitary irradiation prescribed to 0.5 cm below the mucosa. Ninety percent of the LDR group and 92% of the HDR group completed treatment within < 56 days. Treatment-related toxicities were scored according to the GOG toxicity scale. Mean and median follow-up times were 101 months and 111 months (3-172 months) for the LDR group and 42 and 40 months (3-98 months) for the HDR group. RESULTS: The 5-year disease-free survival was 89% for the LDR group and 72% for the HDR group. Local control was observed in 90% (18 out of 20) of the LDR patients and 89% (41 out of 46) of the HDR patients for an overall local control rate of 89.5%. Two of 20 LDR patients (10%) experienced recurrence (two pelvic with distant metastasis). Nine of 46 HDR patients (22%) had recurrence of disease (three pelvic, four distant metastasis, and two pelvic with distant metastasis). In the HDR group, 6 out of 16 (38%) with positive lymph nodes died of disease whereas, 27 out of 30 (90%) of the patients with negative lymph nodes remain free of disease. Three of 20 (15%) LDR patients and 4 out of 46 (9%) HDR patients experienced Grade 2 or 3 late treatment- related complications. No patient in either group had Grade 4 or 5 complications. Pathologic risk factors were analyzed. Lymph node positivity and lymphovascular space invasion were found to be significant (p = 0.01 and p = 0.02). Positive margins, deep invasion, and age were not significant. CONCLUSION: Our results demonstrate the efficacy of postoperative irradiation for cervical cancer with pathologic risk factors. Overall, the local control rate was 89.5% The HDR results demonstrate that this method can be delivered safely and effectively.     

Intraarterial chemotherapy combined with radiation therapy for advanced cancer of the uterine cervix

The results of intraarterial chemotherapy (IACT) combined with definitive radiation therapy for 23 advanced and bulky carcinomas of uterine cervix are reported. IA-CT with cisplatin 50 mg and doxorubicin 30 mg was administered by one shot method in bilateral internal iliac arteries. The protocol consisted of one to three treatment session every 3 weeks. Nine of eleven patients with clinical stage III achieved a complete local response (82%), and the 3- and 5-year survival in these cases were 72% and 72%, respectively. These results were superior to the response (58%), 3- and 5-year survivals (68%, 58%) obtained in 19 patients treated mainly with radiation therapy alone. The side effect of grade 2 and 3 for the intestine, such as ileus and hemorrhagic colitis, was noted in 3 patients (15%). In addition, 3 of 8 patients with radical surgery and postoperative radiation therapy after IA-CT developed insufficient fracture of pelvic bone. These complications accompanied by IA-CT combined with radiation therapy and/or surgery increased slightly, compared with that by the previous therapy without IA-CT, but were not critical. The results suggest that IA-CT following radiation therapy is effective to improve the prognosis of patients with Stage III cervical cancer.     

Results of radical surgical procedures after radiation for treatment of invasive carcinoma of the uterine cervix in a private practice

An analysis is made of the results of treatment of 96 women with carcinoma of the cervix, Stages IB and II, in a private practice. All 96 women were treated preoperatively with uterine intracavitary radium, followed 6 weeks later by Wertheim hysterectomy with pelvic lymphadenectomy. If malignant tumor was present in the lateral pelvic lymph nodes, external radiation was given postoperatively. The over-all survival rates were: Stage IB, 88% and 84% at 5 and 10 years; Stage II, 72% and 62% at 5 and 10 years. Regardless of the clinical stage, the highest survival rates were found in those patients who had no malignancy in the lateral pelvic lymph nodes and no residual cervical carcinoma. The lowest survival rates were found in those patients who had both residual cervical carcinoma and lymph node metastases.     

Experience and results of application of remote afterloading system (RALS) optimization program for intracavitary treatment of squamous cell carcinoma of the uterine cervix

An optimization program for a remote after-loading system (RALS) for intracavitary treatment of cancer of the uterine cervix was established in 1982 by Tabushi and his co-workers. This system has been used in our hospital since 1986, using MODULEX. Seventy-three cases of untreated squamous cell carcinoma of the uterine cervix have been treated under RALS, 29 under conventional RALS and 44 under the RALS optimization program. The cumulative 5-year survival rates were obtained for the groups treated under each system by the Kaplan-Meier method. The 5-year survival rate of stage II cases treated under the RALS optimization program was 68.2%, and that of stage III cases 58.5%. On the other hand, that of stage II cases treated under conventional RALS was 56.3%, and that of stage III cases 44.9%. There was no significant difference between these two groups. Local control rates for stage II and III cases were higher than 5 year-survival rates. Among complications, the frequency of grade 2 radiation colitis was 15.9% with the RALS optimization program cases, and that of grade 2 radiation cystitis was 4.5%. We consider the RALS optimization program to be a clinically useful method for the intracavitary treatment of squamous cell carcinoma of the uterine cervix.     

High-dose rate intracavitary irradiation for carcinoma of the uterine cervix. The adverse effect of treatment prolongation

AIM: To investigate the adverse effect of treatment prolongation on the local control and survival of the cervical carcinoma of the uterus. PATIENTS AND METHOD: Two hundred and sixteen patients with stage IIB and III cervical carcinoma treated with a combination of external radiation and high-dose rate (HDR) intracavitary irradiation between 1978 and 1989 were retrospectively studied. A multivariate analysis was used to determine the effect of treatment time on local control and survival. RESULTS: Overall treatment time was the most highly significant factors for local control in the multivariate analysis (p = 0.0005). The 5-year cumulative relapse rates were significantly different with the treatment times 35 to 42 days: 9% versus 43 to 49 days: 19% versus 50 to 62 days: 42% (p = 0.001). The second most significant parameter was stage classification (p = 0.02). Concerning relapse-free survival, stage classification (p = 0.0001), overall treatment time (p = 0.0035) and hemoglobin level (p = 0.0174) were the 3 most important prognostic factors, although there was no relationship between treatment time and late complications. CONCLUSION: These results suggest that prolongation of treatment time is associated with decreased local control and survival in patients treated with external radiation and HDR intracavitary irradiation.     

Pancreatic duct antibodies and subclinical insufficiency of the exocrine pancreas in Sj?gren''s syndrome]

AIM: To investigate prognostic factors and complications after radical hysterectomy followed by postoperative radiotherapy for carcinoma of the uterine cervix. PATIENTS AND METHODS: One hundred twenty-eight patients with T1b-2b carcinoma of the uterine cervix following radical hysterectomy with bilateral pelvic lymphadenectomy and postoperative radiation therapy were reviewed. Pathologic and treatment variables were assessed by multivariate analysis for local recurrence, distant metastases and cause specific survival. RESULTS: The number of positive nodes (PN) in the pelvis was the strongest predictor of pelvic recurrence and distant metastases. These 2 failure patterns independently affect the cause specific survival. The 5-year cumulative local and distant failure were PN(0): 2% and 12%, PN(1-2): 23% and 25%, PN(2 <): 32% and 57%, respectively (p = 0.0029 and p = 0.0051). The 5-year cause specific survival rates were PN(0): 90%, PN(1-2): 59% and PN(2 <): 42% (p = 0.0001). The most common complication was lymphedema of the foot experienced by one-half of the patients (5-year: 42%, 10-year: 49%). CONCLUSION: These results suggest that patients with pathologic T1b-T2b cervix cancer with pelvic lymph node metastases are at high risk of recurrence or metastases after radical hysterectomy with pelvic lymphadenectomy and postoperative irradiation.     

Results of postoperative radiotherapy in the treatment of sarcoma of the corpus uteri

BACKGROUND: The role of radiotherapy in the treatment of uterine sarcoma still is not clear. Data from the literature advocating adjuvant radiotherapy most often are based on very small patient groups, whereas larger epidemiologic studies, which appear to show no benefit for the additional radiotherapy, lack information regarding clinical data influencing the choice for adjuvant irradiation. METHODS: During 1981-1992, 72 patients were referred for postoperative radiotherapy. Histologic diagnoses were leiomyosarcoma (LMS) in 30 patients, endometrial stromal sarcoma (ESS) in 11 patients, mixed müllerian tumors (MMT) in 28 patients, and other sarcoma types in 3 patients. The 1988 International Federation of Gynecology and Obstetrics classification for endometrial carcinoma was applied retrospectively. Forty patients presented with Stage I disease, 9 with Stage II, 17 with Stage III, and 6 with Stage IV. External beam therapy was given with a cobalt-60 unit using a rotation technique with 2 separate arcs in daily fractions of 2 gray (Gy), up to a total dose of 56 Gy to the pelvis. Brachytherapy was given to the vaginal vault either with 2 radium applications (median: 1600 milligram-hours to the applicator surface) or, in the majority of cases, with 3 fractions of high dose rate afterloading applications (iridium-192, 10-Curie source) with 7 Gy each to an isodose 7.5 mm from the applicator surface. RESULTS: The 5-year actuarial overall survival, disease specific survival, and local control rates for 72 patients were 52.3%, 58.5%, and 77.9%, respectively; in Stage I patients they were 74.8%, 84.6%, and 94.4%, respectively; in Stage II patients they were 53.3%, 53.3%, and 88.9%, respectively; in Stage III patients they were 15.7%, 17.9%, and 55.5%, respectively; and in Stage IV patients they were 0%, 0%, and 0%, respectively. For LMS, the 5-year actuarial overall survival, disease specific survival, and local control rates were 49.4%, 52.0%, and 76.0%, respectively; for ESS they were 81.8%, 81.8%, and 90.9%, respectively; and for MMT they were 42.3%, 54.9%, and 72.4%, respectively. CONCLUSIONS: These data suggest that adjuvant radiotherapy is an effective treatment for uterine sarcoma with regard to disease specific survival in patients with early stage disease and increases local control, even in patients with advanced stage disease.     

Stage I carcinoma of the uterine cervix in patients under 40 years of age

A retrospective analysis was made 94 patients, 39 years of age or younger, who were treated for Stage I carcinoma of the uterine cervix from 1942 through 1972 at the Los Angeles Tumor Institute and the Southern California Cancer Center. Comparisons were made between the frequency of Stage I and other stages of carcinoma of the uterine cervix, as well as the frequency of Stage I carcinoma in young and older individuals. Survival rates for the younger group were compared to those for the same stage of disease for all ages of patients. There is discussion of the treatment modalities used in light of recommendations for future plans of therapy for these young patients. Tumor recurrences are discussed, with special reference to 43 patients who survived over 10 years. Eight of these patients were found to show new or recurrent tumors after this period of time. The importance of careful, long-term follow-up and early secondary treatment for recurrent lesions is emphasized, since subsequent radical surgery may salvage a number of these individuals.     

Method for determining optimal intracavitary radiotherapy conditions for carcinoma of the uterine cervix with tumor infiltration of the vaginal wall

Stage III carcinoma of the uterine cervix is occasionally accompanied by tumor infiltration of the vaginal wall. Currently, the vaginal wall has to be irradiated in the same manner as the uterine cervix. The authors have developed a system for determining the optimal irradiation conditions for treating the two regions, uterine cervix and vaginal wall, at the same time. A comparison of two methods is shown in simulation, and then a clinical case is reported. The first method consists of two treatment plans, one for the uterine cervix without tumor infiltration of the vaginal wall, and the other for the vaginal wall without carcinoma of the uterine cervix. The second, newly developed method considers the two regions together. Irradiation times of ovoid sources obtained with the second method are 15-25% less than those of the first method. Isodose curves obtained with the two methods are very different, and thus the uterine cervix and vaginal wall must be considered together in order to determine irradiation conditions.     

Long term results of treatment of carcinoma of cervix

In this survey of 602 patients treated for carcinoma of the uterine cervix during the period 1944--1968 (with a 100 per cent follow-up) survival rates at 5, 10, 15 and 20 years after radiotherapy were 41, 28, 18 and 11 per cent. The crude five-year cure rate of over 70 per cent for Stage I and 58 per cent for Stage II cases and an overall five-year survival rate of 42 per cent for all stages compares favourably with results published from other institutions in the United Kingdom.     

Radiotherapeutic management of cervical carcinoma that complicates pregnancy

BACKGROUND: Data regarding radiation therapy for pregnant patients with cervical carcinoma are limited. The goal of this study was to assess the effects of pregnancy on tumor control, survival, and morbidity associated with radiation therapy administered to pregnant patients. METHODS: The authors performed a retrospective case-control analysis of 26 women with cervical carcinoma who were diagnosed during pregnancy and treated primarily with radiation therapy. These cases were matched with 26 controls based on age, histology, stage, treatment, and year of treatment. RESULTS: Patients were treated with external beam radiation (mean dose, 46.7 gray [Gy]) and intracavitary radiation (mean dose, 56.5 Gy to Point A). Two patients with Stage IA2 squamous cell carcinoma treated in the third trimester had a planned delay in treatment of 3 weeks, and both infants had an uncomplicated neonatal course. Seven pregnant patients (2 Stage IB1, 5 Stage IB2) underwent radiation after radical hysterectomy was aborted due to positive regional lymph nodes. Three patients diagnosed during the first trimester were treated with radiation with the fetus in situ, and all had spontaneous abortions 20-24 days after the start of radiation (mean dose, 34 Gy). In all these cases, radiation was interrupted for only 3 days or less. There were no statistically significant differences in recurrence rates or survival between the pregnant group and the controls. Short term toxicity was comparable in pregnant and nonpregnant patients and easily controlled. Long term complications were more common in controls (12% in pregnant patients, 27% in controls), but this difference was not statistically significant. Most complications were likely related to radiation techniques (particularly the predominance of cobalt-60). CONCLUSIONS: Planned delay in treatment should be offered to pregnant patients with early stage squamous cell carcinoma in the late second and early third trimester. Patients diagnosed in the first or second trimester who are not good candidates for planned delay in treatment should be given radiation therapy immediately. It may be necessary to reconsider planned radical hysterectomy for pregnant women with Stage IB2 disease due to the high rate of lymph node positivity found on exploration. For patients with advanced disease, radiation therapy appears to be a safe and effective modality.     

Effect of EDTA on reduction of copper toxicity in Oreochromis mossambicus (Peters)

OBJECTIVES: To determine the best therapeutic approach for treatment of patients with urethral cancer according to tumor location and clinical-pathologic stage. METHODS: A retrospective review of 21 consecutive patients diagnosed with primary urethral carcinoma was performed. Clinical-pathologic staging, treatment modality, and outcome were analyzed. RESULTS: The overall survival rate was 62%. In patients with clinical Stage Ta-2N0M0 tumors, 8 of 9 patients (89%) are free of disease compared to 5 of 12 patients (42%) with Stage T3-4N0-2M0 tumors (P = 0.03). Best treatment outcome for patients with Stage T3 disease or higher was obtained when multimodality therapy (neoadjuvant chemotherapy and radiation therapy with or without surgery) was administered, with a disease-free survival rate of 60%. CONCLUSIONS: Clinical-pathologic stage was a strong predictor of disease-free survival rate. For patients with Ta-2N0M0 tumors, multimodality therapy may not be required. Conversely, best treatment outcomes in patients with T3-4N0-2M0 tumors are obtained by administering a multimodal therapy combining chemotherapy and radiation therapy with surgical resection.     

The independence of intrinsic radiosensitivity as a prognostic factor for patient response to radiotherapy of carcinoma of the cervix

A study was made of the prognostic value of pretreatment measurements of tumour radiosensitivity (surviving fraction at 2 Gy, SF2) in 128 patients with stage I-III carcinomas of the uterine cervix undergoing radiotherapy. The median follow-up time was 47 months. In a univariate analysis stratifying patients according to the median value, radiosensitivity was a significant prognostic factor for overall survival, local control and metastasis-free survival. The 5-year survival rate for tumours with SF2 values below the median was 81% and was significantly greater than the rate of 51% for those with SF2 values above the median. In bivariate analyses, SF2 was shown to be independent of disease stage, tumour grade, patient age, colony-forming efficiency and tumour diameter. In a multivariate analysis, radiosensitivity was the most important variable and, after allowing for this, only stage was a significant independent predictor of treatment outcome. These data indicate that, in carcinoma of the cervix treated with radiotherapy, pretreatment tumour intrinsic radiosensitivity is an important prognostic parameter and contributes to prognosis independently of other established and putative parameters.     

Effect of radiologic stage III substage on nonsurgical therapy of non-small cell lung cancer

BACKGROUND: Patients with Stage III non-small cell lung cancer (NSCLC) whose cases are staged or treated surgically have different prognoses, depending on the substage (IIIa, IIIb). It is not known whether the prognostic differences apply to clinically staged nonsurgical cases. The authors wanted to determine whether radiologic Stage III substages, determined by computerized axial tomography (CT) scans, are prognostically important in these patients with NSCLC: In addition, they wanted to determine whether the observed superior survival of selected patients with Stage III NSCLC receiving chemotherapy in addition to radiation therapy (chemo-RT) (Cancer and Leukemia Group B protocol 8433: N Engl J Med 1990; 323:940-5) was influenced by an imbalance in the radiologic Stage III substage. METHODS: Review of pretreatment chest radiographs and CT scans with determination of TNM status and stage was done by the consensus of three readers, who were unaware of which treatment each patient had received (radiation therapy alone [RT] or chemo-RT). RESULTS: Patient characteristics in the two treatment arms were similar. Fifty-five percent of patients receiving RT had Stage IIIa and 33% Stage IIIb disease; in the chemo-RT treatment arm, 73% had Stage IIIa and 25% Stage IIIb disease (P = 0.11). Seven patients (12%) who received RT and one in the chemo-RT treatment arm (2%) had Stage I-II disease on CT scan. Patients with Stage IIIa disease had superior survival to those with Stage IIIb disease (median, 16.5 versus 10.5 months, respectively; P = 0.0045). Within each substage, survival was superior in the chemo-RT (versus RT) treatment arm (Stage IIIa, 17.2 versus 10.7 months, respectively; P = 0.16; Stage IIIb, 12.0 versus 6.9 months, respectively; P = 0.089). CONCLUSIONS: The survival advantage for selected patients with Stage III NSCLC treated with chemo-RT in this study did not result from a more favorable pretreatment radiologic Stage III substage. An advantage for induction chemotherapy was seen in patients with Stage IIIa and IIIb disease. Future studies in this population should prospectively assess and consider stratification for Stage III substage.     

A phase II pilot trial of 13-cis retinoic acid and interferon-alpha in patients with advanced pancreatic carcinoma

BACKGROUND: Advanced unresectable pancreatic adenocarcinoma has a dismal prognosis. The authors previously have shown that retinoic acid (RA) and interferon-alpha (IFN-alpha) inhibit growth and induce differentiation in human pancreatic carcinoma cells in vitro and in vivo. The purpose of this trial was to examine the feasibility and tolerability of a combination therapy of 13-cis RA and IFN-alpha in patients with advanced unresectable pancreatic carcinoma. METHODS: Twenty-two patients (median age, 62 years) with histologically confirmed, unresectable pancreatic adenocarcinoma classified as International Union Against Cancer Stage III (5 patients) or IV (17 patients) were included. Patients received 1 mg/kg body weight 13-cis RA orally and 6 million IU IFN-alpha subcutaneously daily. Restaging by ultrasound, computed tomography scan, and chest X-ray was performed every 2 months. RESULTS: No complete remission and 1 partial remission (PR) (4.5%) were observed. Fourteen patients (63.6%) demonstrated stable disease with a median duration of 5.0 months (range, 2.3-17.7+ months). Toxicity mainly was related to IFN-alpha and predominantly was hematologic (no toxicity was World Health Organization [WHO] Grade 4 and 13.6% were WHO Grade 3). Nonhematologic toxicities did not exceed Grade 2 (skin and oral mucosa) and mainly were related to 13-cis RA. The median survival of the patients with Stage III disease was 8.7 months (range, 6.8-23.9+ months) and was 7.4 months for patients with Stage IV disease (range, 0.9-19.2+ months), resulting in a median overall survival of 7.7 months (range, 0.9-23.9+ months). CONCLUSIONS: Combination therapy with 13-cis RA and IFN-alpha is feasible and well tolerated in patients with advanced pancreatic carcinoma. Based on the median survival rates observed in this study this combination should be investigated further in Phase III trials.     

Sequencing of the alpha-synuclein gene in a large series of cases of familial Parkinson''s disease fails to reveal any further mutations. The European Consortium on Genetic Susceptibility in Parkinson''s Disease (GSPD)

PURPOSE: Tumor hypoxia may be an important factor predicting relapse following radiation therapy. This study was designed to determine the relationship between the oxygenation parameters measured using a polarographic oxygen electrode, prior to and during treatment in patients with cervix cancer, and to assess these results with regard to patient survival. MATERIALS AND METHODS: Forty-three patients had pretreatment oxygen assays performed and measurements repeated following external beam radiation to a median dose of 50 Gy (range 26-52 Gy). Stage distribution showed 15 patients in Stage IB, 17 in Stage II, and 11 in Stage III. The median tumor size was 5 cm (range 3-10 cm). RESULTS: The median proportion of pO2 values <5 mm Hg (the HP5) was 41% following radiation, and the median pO2 was 12 mm Hg. These results were not significantly different from the pretreatment HP5 or pO2 of 37% and 12 mm Hg, respectively. Disease-free survival at 2 years was 50% in patients with posttreatment HP5 < or =50%, compared to 60% when posttreatment HP5 was >50% (p = 0.35). CONCLUSIONS: Unlike pretreatment results, tumour oxygenation measured following external radiation does not appear to be a useful predictive assay in patients with cervical cancer.     

Zamifenacin (UK-76, 654) a potent gut M3 selective muscarinic antagonist, reduces colonic motor activity in patients with irritable bowel syndrome

PURPOSE: Retrospective studies suggest that prolonged treatment time adversely affects control rates of squamous carcinomas managed by radiotherapy. From 1989 to 1994 a prospective clinical trial was conducted to assess the feasibility and efficacy of concomitant boost accelerated superfractionated (CBASF) radiotherapy for advanced uterine cervical carcinoma. METHODS AND MATERIALS: Twenty newly diagnosed patients with FIGO stage III squamous cell carcinoma of the cervix were irradiated using a CBASF regimen. Patients received 45 Gy administered to the whole pelvis in 25 fractions in 5 weeks. On Monday, Wednesday, and Friday of the last 3 weeks, an additional 1.6 Gy boost was given 6 hours after the whole pelvis treatment. The 9 boost treatments, totaling 14.4 Gy, were given via lateral fields encompassing the parametria and primary tumor for a cumulative tumor dose of 59.4 Gy. A single low-dose rate brachytherapy procedure was performed within 1 week after the external beam radiotherapy to raise the point A dose to 85-90 Gy in 42 days. Primary endpoints of analysis were local control, complications, and patterns of failure. Results are compared with the outcomes of 21 patients treated with conventionally fractionated (CF) radiotherapy during the same years. RESULTS: Median total treatment time was 46 days in the CBASF group (range 37-62). Median follow-up interval among surviving CBASF patients is 3.8 years. The four-year actuarial local control rates are 78% and 70% in the CBASF and CF groups, respectively (p = ns). Only 2 CBASF patients required a treatment break because of acute toxicity, but severe late complications occurred in 8/20 CBASF patients for a crude rate of 40%. Distant failure was more common than local failure in the CBASF group, and para-aortic node failure occurred in six of the eight CBASF patients with distant failure. CONCLUSIONS: In the management of stage III cervix cancer, the CBASF regimen produced a trend toward improved local control when compared with the CF regimen, shifting the patterns of failure toward a higher rate of isolated distant failures. The high frequency of para-aortic node failure warrants consideration of elective treatment to this region in stage III patients treated with curative intent. Although the high local control rate of the CBASF regimen supports further investigation of accelerated treatment regimens for locally advanced cervix cancer, the unacceptable risk of late complications necessitates refinement in technique and scheduling to improve the therapeutic ratio.     

Combined surgery and postoperative radiotherapy for carcinoma of the base of radiotherapy for carcinoma of the base of tongue: analysis of treatment outcome and prognostic value of margin status

BACKGROUND: Choice of treatment for base of tongue carcinoma is controversial, with options including surgery alone, radiotherapy alone, or multimodality treatment. Given the highly aggressive nature of these tumors, it has been our institutional policy to manage this disease with combined partial glossectomy (with attempt to avoid laryngectomy if possible) with planned postoperative radiotherapy (RT). We reported on our institutional experience with this approach. METHODS: A retrospective review of the charts of 17 patients with primary base of tongue squamous cell carcinoma treated with surgery and postoperative RT was performed. Patients treated with chemotherapy as part of their management were excluded. All patients underwent partial, hemi-, or subtotal glossectomy; 15/17 patients underwent ipsilateral radical or modified radical neck dissection. All patients received comprehensive postoperative RT (median dose 6000 cGy; range 5040-6920 cGy). Stage distribution was as follows: stage I, 2; stage II, 3; stage III, 2; stage IV, 10. Positive margins for invasive carcinoma were found in 9/17 patients. Median follow-up of surviving patients is 46 months; median follow-up for all patients is 31 months. RESULTS: For the entire group of patients, the actuarial 3-year local-regional control rate was 68%. The actuarial 3-year overall survival rate was 46%. The local-regional control rate was 83% for patients with stage I-III disease versus 50% for stage IV disease. There were no local failures among eight patients with negative margins (local control 100%) compared with an actuarial local control rate of 36% among patients with positive margins (p = .03). Survival, disease-specific survival, and locoregional control were also highly correlated with margin status (p = .003). Late major complications included 5/17 patients requiring permanent G-tubes and/or tracheostomy to prevent aspiration. CONCLUSIONS: Surgery plus postoperative RT is an intensive treatment for carcinoma of the base of tongue which offers high locoregional control in patients in whom negative margins are achieved. Positive margins indicate a high risk of locoregional and systemic failure, and these patients should be considered for innovative clinical trials after surgery.     

Results and prognostic factors in the retreatment of locally recurrent nasopharyngeal carcinoma

PURPOSE: To review the results and evaluate the prognostic factors in the retreatment of locally recurrent nasopharyngeal carcinoma. METHODS AND MATERIALS: We reviewed the records of 74 patients with locally recurrent nasopharyngeal carcinoma treated at the University of California, San Francisco between 1957 and 1995. The histologic types included squamous cell carcinoma in 6 (8.1%), nonkeratinizing carcinoma in 48 (64.9%), and undifferentiated carcinoma in 20 (27%) cases. The site of recurrence was in the primary in 46 (62.2%), in the neck nodes in 20 (27%), and in both sites in 8 (10.8%) patients. The recurrent disease was Stage I in 10 (13.5%), Stage II in 16 (21.6%), Stage III in 20 (27%), and Stage IV in 28 (37.9%) patients. Thirty-seven (50%) patients developed recurrence within 2 years and 58 (78.4%) within 5 years after initial treatment. Radiotherapeutic techniques used in the retreatment of primary recurrence consisted of external beam radiotherapy (EBRT), intracavitary brachytherapy, heavy-charged particle beam, and gamma knife, alone or in combination. Reirradiation doses ranged from 18 to 108 Gy, with a median dose of 60 Gy. Treatment of recurrent neck nodes consisted of radical neck dissection (RND) +/- intraoperative radiotherapy (IORT), or EBRT +/- hyperthermia, or chemotherapy +/- hyperthermia. Chemotherapy was used in 22 (30%) patients. Median follow-up was 20 months (range: 2 to 308 months). RESULTS: The 3-, 5-, and 10-year actuarial overall survival following retreatment were 49, 37, 18%, respectively. Thirty-six patients (49%) were free of further local-regional recurrence after retreatment. The 3-, 5-, and 10-year local-regional progression-free rates were 52, 40, and 38%, respectively. On univariate analysis, histologic type (p < 0.0001), interval to recurrence (p = 0.034), and treatment modality for early-stage disease (p = 0.01) were significant prognostic factors for overall survival, with age being marginally significant (p = 0.053). For local-regional progression-free rate, only histology was significant (p = 0.035). On multivariate analysis, age (p = 0.026), histology (p = 0.015), and interval to recurrence (p = 0.030) were significant for overall survival, and only histology (p = 0.002) and presence of complications (p = 0.016) were significant for local-regional progression-free rate. Of the 64 reirradiated patients, late complications were documented in 29 (45%) patients. The late complications were permanent in 21 (33%) and severe in 15 (23%) patients. CONCLUSION: Retreatment using radiotherapy alone or in combination with other treatment modalities can achieve long-term local-regional control and survival in a substantial proportion of patients with locally recurrent nasopharyngeal carcinoma. Age, histology, and interval to recurrence were independent prognostic factors for overall survival, but only histology and presence of complications were significant for local-regional progression-free rate.     

Clinical staging of oropharyngeal carcinoma: a critical evaluation of a new stage grouping proposal

BACKGROUND: An alternative to the International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) stage grouping system was proposed for patients with oropharyngeal carcinoma by Hart et al. (1995) on behalf of the Dutch Head and Neck Oncology Cooperative Group. The system was created by regrouping the T, N, and M categories without redefining the categories themselves. METHODS: Data related to epidemiology, treatment, and survival from 224 previously untreated patients with oropharyngeal carcinoma were analyzed. Staging was performed according to the 1992 UICC/AJCC criteria and according to the proposed stage grouping system. Kaplan-Meier estimates of overall survival were compared for both staging systems; and in a Cox proportional hazards regression analysis, the influence of the variables age, gender, subsite and side of tumor location, histopathologic grade, form of treatment, and stage distribution (according to 1992 UICC criteria and that proposed by Hart et al.) on overall survival was determined. RESULTS: The proposed staging system showed a more balanced distribution of patients (16% in Stage I, 37% in Stage II, 14% in Stage III, and 33% in Stage IV compared with 5% in Stage I, 7% in Stage II, 21% in Stage III, and 67% in Stage IV according to UICC/AJCC 1992 staging). Furthermore, the proposed staging system showed better prognostic discrimination for overall survival (5-year survival rates according to the staging system of Hart et al. were 59% in Stage I, 31% in Stage II, 28% in Stage III, and 16% in Stage IV, vs. 61% in Stage I, 59% in Stage II, 32% in Stage III, and 24% in Stage IV according to UICC/AJCC 1992 staging). CONCLUSIONS: The results are in concordance with the results published by the Dutch Head and Neck Oncology Cooperative Group. It is possible to improve the current staging system by regrouping the T, N, and M categories. [See editorial on pages 1611-2, this issue.]