Results of radiation therapy in the treatment of epithelial carcinoma of the ovary

Between 1967 and 1976, 82 patients who had epithelial carcinoma of the ovary and were treated with surgery and postoperative radiation therapy, respectively, were studied. Of these patients, 35% had Stage I disease, 16% Stage II, 45% Stage III, and 4% Stage IV. Serous cystadenocarcinoma was the histologic cell type in 54% of the patients, and mucinous cystadenocarcinoma was involved in 24%. Of the tumors, 35% were Grade 1, 34% Grade 2, 18% Grade 3, and 13% were unspecified. Survival at five years was 96% for Stage I patients, 60% for Stage II, and 60% for Stage III. No stage IV patient survived past two years. Stage III patients with no palpable tumor prior to radiation therapy did well, with 80% alive at more than two years, while only 10% of Stage III patients with palpable tumors prior to radiation therapy are alive. Patients with Stage III disease treated by whole-abdominal irradiation with a pelvic boost did better than those who received 3,000 rad or less to the pelvis. Radiation therapy continues to be an important treatment modality in epithelial carcinoma of the ovary, particularly in patients with minimal tumor burden.     

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.     

Squamous cell carcinoma of the supraglottic larynx without clinically detectable lymph node metastases: problem of local relapse and influence of overall treatment time

From January 1965 until December 1979, 203 patients with squamous cell carcinoma of the supraglottic larynx were treated with curative intent. The mean follow-up time was 10 years. The policy was to try to aim for cure by radiation therapy (RT) only, reserving surgery (S) for radiation therapy failures. For 193 patients the treatment consisted of a first series of radiation therapy to a total dose of 40 Gy; if a good response to radiation therapy was obtained, the treatment was continued to a full course of 60-70 Gy (RT-I, n = 132). Patients with tumors considered to have responded poorly to the first series of radiation therapy but who refused surgery or were found medically unfit for operation, were also carried to a full dose of 60-70 Gy (RT-II, n = 33). Surgery was performed in 33 cases; 23 patients had a laryngectomy because of a poor response to radiation therapy and 10 were treated with surgery upfront because of severe respiratory distress. This paper focuses on the local control and survival in the defined treatment groups. In summary, with advancing T-stage a lower survival and higher local relapse rate was found; that is, a 5-year relapse-free survival (RFS) of 53% and corrected survival (CS) of 83% for T2 tumors vs 39% (RFS) and 52% (CS) for T4 tumors. Age more than 60 was associated with a 2.2 times higher risk of dying due to laryngeal cancer. A lower relapse-free survival (T3,4: 43% vs 61%) but a comparable corrected survival (T3,4: 64% vs 69%) for RT-I patients compared to the surgery treated patients was found, due to salvage of the radiation therapy failures. Although the relapse-free survival of RT-I and RT-II was similar (43% vs 38%), the corrected survival for the RT-II patients was worse (44% vs 69%). No influence of dose (Gy) per se on the local relapse rate was observed; however, a positive association between local relapse rate with overall treatment time was found. Death from intercurrent disease was almost twice as high as might have been expected for the normal Dutch population. More than half of the patients who died of intercurrent disease developed a second primary tumor.     

Glottic carcinoma. The roles of surgery and irradiation

The treatment of 336 patients with squamous cell carcinoma of the glottic larynx seen at the University of Virginia Medical Center from 1960 through 1977 was reviewed. Two hundred eighty-five patients form the basis of this report. Patients were grouped by stage and by other prognostic factors. Five-year actuarial survival, recurrences, salvage therapy, complications, second primaries, and incidence in patients younger than 45-years-old were examined. The actuarial 5-year survivals are Stage I, 96%; Stage II, 88%; Stage III, 65%; and Stage IV, 57%. Early glottic carcinoma responded equally well to radiation therapy or surgery, and mortality from intercurrent disease was more common than death from glottic carcinoma. Anterior commissure involvement was not found to significantly decrease prognosis in Stage I disease. Within Stage II, patients with impaired true cord mobility had a significantly decreased survival, 71%, versus 93% for Stage II carcinoma with mobile cords. Surgery was superior to irradiation when cord mobility was impaired or fixed. Surgical salvage was successful in 70% of cases when the cords were originally mobile but 11% when cord motion had been impaired or fixed. Patients younger than age 45 years presented with more advanced disease, but by stage, treatment response did not differ from the remaining older group. Based on this review and from data reported in the literature, the authors recommend curative radiation therapy in patients with glottic carcinoma where the vocal cords are fully mobile. When cord mobility is impaired or fixed, the inclusion of surgery in the initial management results increased survival over irradiation alone. Recognizing that glottic carcinoma is often part of a multisystem disease, individualization of treatment is especially important in these advanced tumors.     

Radiation therapy in the management of medically inoperable carcinoma of the lung: results and implications for future treatment strategies.

Surgery is the treatment of choice for resectable non-small cell lung carcinoma. For patients who are medically unable to tolerate a surgical resection or who refuse surgery, radiation therapy is an acceptable alternative. We reviewed the records of 152 patients with medically inoperable non-small cell lung carcinoma treated at our institution between 1982 and 1990. Patients with metastatic disease, mediastinal lymph node involvement or unresectable tumors were excluded. The actuarial overall survival at 2 and 5 years was 40% and 10%, respectively. The disease-free survival at 2 and 5 years was 31% and 15%. The disease-free survival for patients with T1 tumors was 55% at 2 years, versus 20 and 25% for T2 and T3 lesions, respectively (p = .0006). Increasing tumor dose was also associated with increasing disease-free survival (p = .0143). Overall, 66% percent of the patients were considered to have failed. Of these, 70% showed a component of local failure and 45% failed distantly. Patients with T1 tumors experienced a lower probability of failing locally or distantly than did patients with T2 or T3 tumors. A reduced risk of local and distant failure was seen for patients treated to doses of greater than 65 Gray, especially for T1 tumors. We conclude that radical radiation therapy is an effective treatment for small tumors when treated to doses of 65 Gray or more. Since local failure is the prominent pattern of relapse in patients with large tumors, new therapeutic strategies should be considered for this patient group.     

Radiation therapy of anal epidermoid carcinoma

Between 1978 and 1984, 44 consecutive patients with anal epidermoid carcinoma were either given radiation therapy alone (cloacogenic type) or in combination with Bleomycin (squamous type). The patients with small tumors (T1-T2) were treated to 65 Gy or 60 Gy + Bleomycin directly, whereas patients with moderately advanced tumors (T3) were treated to the same radiation dose, only if no evidence of residual disease existed after 50-55 Gy (40-45 Gy + Bleomycin); if a palpable tumor still remained 3 weeks after the irradiation, surgery was performed. Patients with tumors in Stage T4 were treated to 60-65 Gy (+/- Bleomycin) followed by surgery. The outcome has so far been excellent. All but four patients, treated according to the regimen and with no initial metastases, are alive and well; two died postoperatively, one developed urinary bladder recurrence, and one liver metastases. Nineteen patients have a preserved anal function. Only one of the 9 patients also treated with an abdomino-perineal excision had viable tumor at surgery. It is concluded that patients with an anal carcinoma can be safely treated with preservation of the anus in a significant proportion of the cases, and that a combined treatment approach most likely improves survival.     

Long-term treatment results of postoperative radiation therapy for advanced stage oropharyngeal carcinoma.

BACKGROUND. The authors report the long-term treatment results for advanced stage base of tongue (BOT) and tonsillar fossa (TF) carcinomas treated with surgery and postoperative radiation therapy (RT) at Memorial Sloan-Kettering Cancer Center. METHODS. Between 1973 and 1986, 51 patients with squamous cell carcinoma of the BOT (n = 31 patients) and TF (n = 20 patients) were treated with surgery plus RT. Indication(s) for RT included: advanced disease (Stage T3/T4, 34 patients [66%]); close or positive margins (33 patients, 64%) and multiple positive neck nodes (43 patients, 84%). RESULTS. The 7-year actuarial local control rates for BOT and TF lesions were 81% and 83%, respectively. Local control was achieved in 17 of 18 (94%) patients with T3 lesions, and 12 of 16 (75%) patients with T4 lesions. Among patients with positive or close margins who received postoperative doses of 60 Gy or more, the long-term control rate was 93%. The presence of a treatment interruption had a negative effect on the local control rates. The actuarial control among patients who required a treatment break was 64%; for those not requiring interruption of their treatment, the actuarial control was 93% (P = 0.05). At 7 years, the overall survival for all patients was 52%, and the disease-free survival was 64%. The actuarial incidence of neck failure was 21% and 18% for BOT and TF, respectively. The likelihood of having distant metastasis at 7 years for all patients was 30%. The actuarial incidence of having a second malignancy was 35% for patients with BOT disease. Second malignancy was not observed among patients with TF lesions. CONCLUSIONS. The authors conclude that surgery and postoperative RT can provide excellent long-term, disease-control rates for patients with advanced BOT and TF tumors. However, current strategies for BOT lesions have been directed at tongue preservation without surgery.     

Vulvar carcinoma

: Controversies exist regarding the use of radiation therapy in the treatment of vulvar carcinoma. A retrospective review was performed to evaluate our institution's experience with surgery and radiation for this disease.

: The medical records of 47 patients treated for squamous cell carcinoma of the vulva at out institution (1974–1992) were reviewed for TNM stage (AJCC criteria), treatment modality, and associated 5-year local control and survival based on Kaplan-Meier analysis.

: Twenty-eight patients (60%) presented with Stage I and II disease and their 5-year survival was 69%. Stage III patients accounted for 12 (25%) of the patients and their 5-year survival was 73%. Seven patients presented with Stage IV disease and five died within 13 months of diagnosis after predominantly palliative therapy. The 40 patients with Stages I, II, and III disease were treated aggressively and were further evaluated for treatment-modality-associated survival and local control. Radiation therapy was used as primary treatment in nine patients, or whom seven were treated with radiation alone and two were treated postoperatively after wide excision. Surgery alone was performed in 31 patients consisting of either radical vulvectomy (20 patients) or wide excision (11 patients). When comparing outcomes of radical vulvectomy vs. radiation therapy, we noted that the 5-year actuarial survivals were comparable (74% for either modality), despite the presence of more favorable prognostic factors in the group treated with radical vulvectomy. Patients treated with wide excision alone had a trend for a poorer 5-year actuarial survival (51%) and local control (50%).

: Radical vulvectomy offers good locoregional control and survival. This retrospective review further supports the use of radiation therapy with conservative surgery as an alternative treatment option for patients with vulvar carcinoma treated with curative intent. In contrast, the use of wide excision alone should be performed with caution due to a higher locoregional failure rate. The role of appropriately prescribed radiation therapy should be further investigated in prospective clinical trials.     

Effects of irradiation on mixed müllerian tumors of the uterus.

A retrospective study of 54 patients with histologically proven malignant mixed müllerian tumors of the uterus was undertaken with main emphasis on the evaluation of the effects of irradiation on pelvic tumor control. The tumors were staged according to the FIGO classification for endometrial carcinoma and 24 were classified as Stage I, 10 as Stage II, 13 as Stage III and seven as Stage IV. Patients with Stage I and II were treated with surgery alone (9 patients, three surviving) or preoperative intracavitary irradiation (13 patients, eight surviving) or preoperative combination of intracavitary and external irradiation (12 patients, six surviving). Five patients with Stage III and IV were treated with surgery alone, two were treated with a combination of irradiation and surgery and 11 with radiation alone. None of these patients survived. In seven patients showing no residual tumor in the uterine specimen after irradiation, no pelvic failures were noted, whereas seven of 17 (41.2%) with residual tumor developed pelvic recurrences. In patients with Stage I treated with surgery alone, three out of six recurred in the pelvis whereas only three of 17 (17%) receiving preoperative irradiation developed pelvic recurrences. However, in Stage II six of eight patients treated with preoperative irradiation failed in the pelvis. Correlation with the doses of irradiation given to the uterus or the pelvic lymph nodes indicate that with doses below 5000 rads a significantly higher number of pelvic recurrences take place, whereas these are uncommon with doses over 6000 rads. The difference in pelvic recurrences between dosage levels is not, however, statistically significant. It is suggested that patients with Stage I and II malignant mixed müllerian tumors of the uterus should be treated with preoperative radiation and total hysterectomy with bilateral salpingo-oophorectomy. Patients with more advanced disease have extremely poor prognosis and should be treated with radiation therapy alone. This tumor has a high propensity to spread through lymphatics and hematogenous metastases are seen in approximately 75% of the patients. Because of this dissemination, significant improvements in survival rate will not be seen until effective cytotoxic agents are available.     

Results of multimodality therapy for squamous cell carcinoma of maxillary sinus

BACKGROUND: A wide variety of modalities, including surgery, radiation therapy, and chemotherapy, alone or in combination, have been used for the treatment of squamous cell carcinoma (SCC) of the maxillary sinus to obtain better local control and maintain functions. However, there is still much controversy with regard to the optimum treatment. METHODS: From 1987 to 1999, 33 patients with SCC of maxillary sinus were treated at the Department of Otolaryngology-Head and Neck Surgery, University of Tokyo Hospital. The treatment consisted of 30-40 grays (Gy) of preoperative radiotherapy with concomitant intraarterial infusion of 5-fluorouracil and cisplatin followed by surgery and 30-40 Gy of postoperative radiotherapy, for tumors without skull base invasion. For tumors invading the skull base, preoperative systemic chemotherapy with or without radiotherapy was performed, instead of intraarterial chemotherapy, then followed by skull base surgery. The surgical procedures varied according to the extent of tumor. Results were compared with those of the 108 patients treated in our hospital from 1976 to 1982. RESULTS: Partial maxillectomy was performed in 2 T2 patients and 12 T3 patients. Total maxillectomy was performed in 1 T2 patient, 3 T2 patients, and 7 T4 patients. Skull base surgery was performed in eight T4 patients. Orbital content and hard palate were preserved in 22 patients and 18 patients, respectively. The overall 5-year survival rates were 86% in T 3 patients and 67 % in T4 patients, respectively. CONCLUSIONS: Our multimodal treatment has provided favorable local control and survival outcome with good functional results.     

Radiation therapy in early carcinoma of the true vocal cords (stage I and II)

Seventy-four patients with Stage I and twenty patients with Stage II carcinoma of the true vocal cords received radiation therapy from 1971 to 1983. Sixteen patients had second primary cancers with the most common site being the lung. The patients were treated with 4 MeV linear accelerator X ray or 60Co machine with the average total dose of 6600 rads in 33 fractions, 5 days a week by parallel opposing ports. Local control rate by radiation therapy was 86% in Stage I and 70% in Stage II. Eight of twelve (8 of 12) failures were salvaged by surgery. The actuarial 5-year survival was 92 and 80%. Seventy-six (76%) of patients had good quality of voice after treatment.     

Survival and failure analysis in stage II endometrial cancer using the revised 1988 FIGO staging system

Fifty-one patients with Stage II endometrial carcinoma diagnosed between 1974 and 1987 were restaged according to the FIGO 1988 revisions for endometrial carcinoma. Patients were divided into Stage IIA, those patients with cervical glandular involvement without stromal invasion, and Stage IIB, those patients having stromal invasion of the cervix. Tumor grade was also assessed. Patients were treated with radiation therapy alone, pre-operative radiation therapy followed by a simple hysterectomy, or a simple hysterectomy followed by postoperative radiation therapy. The 5-year actuarial survival for Stage IIA was 86% and the 5-year actuarial survival for Stage IIB was 46% (p = 0.06). The 5-year local recurrence rate in each group was 9%. Stage IIA had a distant metastases rate of 14% whereas 44% of the patients in Stage IIB developed distant disease (p = 0.06) at 5 years. The grade of the tumor did not play a role in local recurrence. However, when tumor grade was analyzed with respect to distant disease, 14% of patients with grade 1 tumors developed distant metastases, 31% of patients with grade 2 tumors developed distant metastases, and most significantly, 63% of patients with grade 3 tumors developed distant metastases (p = 0.004). There was no statistically significant relationship between stromal invasion and tumor grade. This study concludes that grade is the greatest predictor of survival, with only 37% of grade 3 patients surviving at 5 years. As a predictor of survival, stromal invasion is of less significance than grade (p = 0.06 vs. p = 0.004). Death most often occurs because of distant metastases, and local failure is rare and is not dependent on the degree of cervical involvement or grade.     

Radiotherapy with or without misonidazole for patients with stage IIIB or stage IVA squamous cell carcinoma of the uterine cervix: preliminary report of a Radiation Therapy Oncology Group randomized trial

Between August 1980 and November 1984, 119 patients with FIGO Stage IIIB or IVA squamous cell carcinoma of the uterine cervix were randomized to receive radiation therapy (4600 cGy pelvis plus 1000 cGy parametrial boost) followed by intracavitary or external boost to the primary with or without misonidazole (MISO) (400 mg/m2 daily 2 to 4 hours prior to radiation therapy). Patients in the two treatment groups were evenly distributed with respect to stratification variables including stage, Karnofsky Performance score, and positivity of para-aortic nodes. Eighty-nine percent of patients had Stage IIIB disease and 88% had a Karnofsky score of 80 or better. Seventy-five percent of patients treated with radiation therapy alone and 79% of patients treated with radiation therapy plus MISO received a boost via intracavitary application. Life threatening (Grade 4) complications occurred in 5 patients receiving radiation therapy alone and one patient receiving radiation therapy plus MISO. MISO toxicity (Grade 3) was limited to severe nausea and vomiting in two patients. With 119 evaluable patients and a median follow-up of 33 months, 64% of patients receiving radiation therapy alone are alive at 18 months compared with 54% for patients assigned to radiation therapy plus MISO. The median survival for patients treated with radiation therapy alone and radiation therapy plus MISO was 1.9 years and 1.6 respectively. At this point in the study the difference in survival is inconsistent with the hypothesis of an improvement associated with MISO. There have been 23 deaths among the 49 patients treated with radiation therapy plus MISO who have been followed for at least 18 months compared with 17 deaths in 48 patients treated with radiation therapy alone. The chance of observing this number of deaths with radiation therapy plus MISO if the addition of MISO improves survival by 10 to 20% is 0.003 and less than 0.001, respectively. The addition of MISO to radiation failed to improve survival for these patients. The results cannot be explained by an uncharacteristically high survival on the radiation therapy alone arm or by an imbalance in the distribution of prognostic factors. Local-regional control remains a problem in the management of patients with advanced cervical carcinoma. More effective and less toxic radiosensitizing agents are needed.     

High-dose radiation therapy in carcinoma of the pyriform sinus

In a retrospective analysis of 61 patients with carcinoma of the pyriform sinus, treated primarily with high doses of radiation therapy with surgery reserved for persistent or recurrent tumor, survival rates of 56.5% and 12.4% were found in Stages III and IV, respectively. The two patients with Stage II disease were cured. There were no Stage I patients. The local control of T4 lesions and N2-3 lesions, as well as the survival of patients with Stage IV disease, is poor with radiation alone. This points out the necessity of combining irradiation with surgery and/or chemotherapy for Stage IV disease. The results in early stages with radiation alone are acceptable.     

Preoperative radiation therapy followed by extrafascial hysterectomy in patients with stage II endometrial carcinoma

Seventy-four patients with Stage II endometrial cancer were treated by a combination of preoperative radiation therapy followed by extrafascial hysterectomy, bilateral salpingo-oophorectomy, and paraaortic lymph node sampling at the University of Kentucky Medical Center from 1967 to 1988. All patients had histologically confirmed endometrial cancer with involvement of the endocervix. The cell types and numbers of the tumors treated were as follows: adenocarcinoma, 58; adenoacanthoma, six; adenosquamous carcinoma, nine; and clear cell carcinoma, one. Preoperative radiation consisted of 4500 cGy external therapy followed by one intracavitary implant providing an additional 2000 cGy to point A. Surgery was done 4 to 6 weeks after completion of radiation therapy. Five patients (7.1%) had paraaortic lymph node metastases. Four were treated with extended-field radiation therapy and one with platinum-based combination chemotherapy. After treatment, the patients were followed at regular intervals from 2 to 22 years (mean, 5.4 years). Eleven patients (15%) had recurrent cancer, with the vagina and upper abdomen being the most common sites of spread. The estimated 5-year and 10-year disease-free survival rates of these patients are 88% and 76%, respectively. Cell type, depth of myometrial invasion, and lymph node status were the most important prognostic variables in the patients evaluated. These data confirm that the combination of preoperative radiation therapy and surgery produces excellent long-term survival in patients with Stage II endometrial cancer.     

Radiation therapy for early-stage carcinoma of the oropharynx

PURPOSE: To evaluate the outcomes of radiation therapy treatment of patients with Stage I and II squamous cell carcinoma (SCC) of the oropharynx and discover adverse prognostic factors that may help select a subgroup of patients for a different management approach. METHODS AND MATERIALS: A search of the database maintained by the Department of Radiation Oncology of The University of Texas M. D. Anderson Cancer Center for patients with Stage I or II SCC of the oropharynx was performed. This search identified 175 patients treated between 1970 and 1998 who met the inclusion criteria for this retrospective study. Distribution of primary sites was: tonsillar fossa/pillar, 60 patients; soft palate, 55 patients; base of tongue, 40 patients; and pharyngeal wall, 20 patients. Twenty-five patients were stage T1, 124 were T2, and 26 were Tx. All patients were treated with fractionated radiation to a median dose of 66 Gy. Eighty-five patients were treated with conventionally fractionated radiation, 73 were treated with the concomitant boost fractionation schedule, and the remaining 17 were treated with other altered fractionation schedules or with intraoral or interstitial boosts. RESULTS: The median follow-up for all patients was 76 months (range, 2-302 months). The actuarial 5-year local control (LC), regional control, locoregional control (LRC), and disease-free survival (DFS) rates were 85%, 93%, 81%, and 77%, respectively. Only 7 patients (5%) with LC developed nodal metastases, and 10 patients (7%) with LRC developed distant metastases. Eleven patients (32%) with locoregional recurrence were rendered without evidence of disease after a surgical salvage procedure, resulting in a 5- year ultimate LRC rate of 87%. T-stage classification was statistically significant (p = 0.03) in univariate analysis for actuarial 5-year LRC, 88% for Stage I vs. 72% for Stage II. The 5- and 10-year disease-specific survival rates were 85% and 79%, respectively, while the actuarial 5- and 10-year overall survival rates were 70% and 43%, respectively. Fifty-one patients (29%) developed second primary tumors, 86% of which were cancers of the upper aerodigestive tract (UADT). Heavy alcohol consumption was associated with both an increased risk of disease recurrence and development of a second cancer of the UADT. CONCLUSIONS: Patients with early-stage oropharynx cancer have high rates of disease control when treated with radiation. Lymphatic and hematogenous metastases are uncommon. Surgical salvage of disease recurrence is successful in approximately one-third of patients. As the majority of recurrences occur within the first 2 years from treatment, close observation during this time period is important. The development of second primary tumors of the UADT adversely impacts survival in these patients to as great a degree as the index cancer.     

The role of postoperative radiation therapy in carcinoma ex pleomorphic adenoma of the parotid gland

PURPOSE: To evaluate the impact of postoperative radiation therapy on the clinical course of patients with carcinoma ex pleomorphic adenoma of the parotid gland. METHODS AND MATERIALS: Between 1960 and 2004, 63 patients were treated with definitive surgery for carcinoma ex pleomorphic adenoma of the parotid gland. Forty patients (63%) received postoperative radiation therapy to a median dose of 60 Gy (range, 45-71 Gy). Adenocarcinoma (29 patients), salivary duct carcinoma (16 patients), and adenoid cystic carcinoma (9 patients) were the most common malignant subtypes. Pathologic T -stage was: 16% T1, 33% T2, 32% T3, and 19% T4. Twenty-one patients (33%) had microscopically positive margins and 39 (62%) had perineural invasion. Median follow-up was 50 months (range, 2-96 months). RESULTS: The use of postoperative therapy significantly improved 5-year local control from 49% to 75% (p = 0.005) and was associated with an improvement in survival among patients without evidence of cervical lymph node metastasis (p = 0.01). A Cox proportional hazard model identified pathologic involvement of cervical lymph nodes as an independent predictor of overall survival. Overall survival was 16% for patients with pathologic N-positive disease compared with 67% for those whose lymph node status was negative or unknown (p = 0.001). CONCLUSION: Surgery followed by postoperative radiation should be considered the standard of care for patients with carcinoma ex pleomorphic adenoma.     

Treatment of childhood germ cell tumors. Review of the St. Jude experience from 1979 to 1988.

BACKGROUND. The outlook for patients with germ cell tumors was poor before the advent of effective chemotherapy. The authors assessed the outcome of treatment with multiagent chemotherapy (with or without radiation therapy) in children treated for germ cell tumors at St. Jude Children's Research Hospital (SJCRH). METHODS. Sixty children with germ cell tumors were treated between January 1979 and June 1988. Postsurgical treatment was based on tumor site, stage, and histology. Most patients received chemotherapy with vincristine, actinomycin-D, and cyclophosphamide (VAC), or a modified Einhorn regimen (cisplatin, bleomycin, and vinblastine [PVB]); in the absence of response to initial therapy, patients received alternating courses of VAC and PVB (VAC/PVB regimen). Exceptions were patients with Stage I testicular tumors (observation only) and ovarian germinomas (Stage I tumors measuring less than 10 cm, observation only; tumors larger than 10 cm or Stage II-III disease, radiation only; and Stage IV disease, VAC plus radiation). RESULTS. The estimated 5-year survival is 100% for patients with Stage I disease (n = 18), 87% for patients with Stage II (n = 8), 72% for Stage III (n = 25), and 56% for Stage IV (n = 9). Patients with testicular tumors of any stage or with Stage I-II ovarian tumors had 100% 5-year survival. Extragonadal tumors responded poorly to VAC alone with recurrent or progressive disease in eight of nine patients. Treatment for those tumors was changed to alternating courses of VAC and PVB, which failed in only one of seven patients. Nine of 19 patients with advanced ovarian tumors had disease recurrence with VAC; these patients then received PVB, which was effective in four cases. CONCLUSIONS. For patients with advanced germ cell cancers, intensification of therapy or the development of new approaches is necessary. In contrast, future trials in children with limited stage should focus on reducing acute and long-term toxicities.     

Thoracic irradiation with or without levamisole (NSC #177023) in unresectable non-small cell carcinoma of the lung: a phase III randomized trial of the RTOG

A total of 285 patients with medically inoperable (RTOG Stage T1-2, N0-1) or unresectable (RTOG Stage T3, N0-1) non-small cell carcinoma of the lung were randomized by the Radiation Therapy Oncology Group (RTOG) to receive radiation therapy (6000 cGy total dose/6 weeks) plus levamisole (2.5 mg/kg twice weekly for 2 years or until tumor progression) or a placebo. One hundred twenty-nine evaluable patients were assigned to placebo and 131 to levamisole. This report is based on 260 (91%) eligible patients who started treatment and have adequate follow-up. Fifty percent of the patients in both treatment groups had Karnofsky scores of 90-100; 72% had squamous cell carcinoma, 12% adenocarcinoma, and 16% large cell undifferentiated carcinoma; 60% had RTOG Stage I or II primary tumors and 40% had Stage III (T3, N0-1) tumors. Complete regression of tumor was reported in 20% of the patients treated with levamisole and 36% of those receiving placebo. An additional 33% and 19%, respectively, had a partial response (trend test p = 0.08). Median survival was 9 months for patients treated with levamisole and 12 months for those on placebo (two-sided p less than 0.01); at 2 years, patients treated with levamisole had a 15% survival rate as compared to 24% in those receiving placebo. The cumulative proportion failing within the irradiated field with or without other sites of progression at 2 years was 30% in the levamisole group and 34% in the placebo patients. Median progression-free survival was 6 months for patients on levamisole and 7 months for those on placebo (overall two-sided p = 0.014); the estimated proportions progression-free at 2 years were 11% and 18%, respectively. The study showed no significant prolongation of survival, progression-free survival, or differences in patterns of failure in irradiated patients treated with levamisole compared with a placebo. Toxicity related to this immunoadjuvant was, in general, of moderate clinical importance. This study confirms a report by the Southeastern Cancer Study Group concluding that levamisole combined with definitive irradiation has no benefit in the treatment of unresectable non-small cell carcinoma of the lung.     

The use of radiation therapy in the management of minor salivary gland tumors

Between 1964 and 1985, 52 patients were treated with curative intent by radiation therapy alone or in combination with surgery for malignant tumors of minor salivary gland origin. All patients had a minimum follow-up of 2 years, and 80% had a minimum follow-up of 5 years. Twenty-six (50%) were adenoid cystic carcinomas; the remaining histologies included adenocarcinoma, mucoepidermoid carcinoma, and malignant mixed tumors. The most common sites of origin were in the oral cavity/oropharynx (49%) and the nasal cavity or paranasal sinuses (40%). Twenty-seven patients (52%) presented with an advanced or unresectable stage (AJCC Stage III or IV, extensive bone or nerve invasion, or tumor greater than 5 cm). Treatment was highly individualized; 50% of the patients received radiation therapy alone, and 50% received combined treatment with either postoperative or preoperative radiation therapy. Early-stage minor salivary gland tumors were controlled equally well with radiation therapy alone or with a combined approach. For the advanced tumors, a combined approach yielded significantly superior absolute local control rates as compared with radiation therapy alone (10/13 vs. 2/13). For adenoid cystic carcinoma, the local control rate at 10 years was 45% (actuarial); the tumor was not controlled locally in any patients with advanced/unresectable stage who were treated with radiation therapy alone. The absolute local control rate was 75% for 4 early-stage tumors treated with radiation therapy alone and 60% for 5 advanced tumors treated with a combined approach. The average time to local recurrence was 67 months for adenoid cystic carcinoma. Severe complications of radiation therapy occurred in 11 (27%) of 40 evaluable patients, with unilateral blindness being the most common. Seven of 9 patients who became blind had unresectable disease with close proximity to or invasion of the orbit. A time-dose analysis is also presented.