Intracranial ependymomas in children

Between 1970 and 1988, 51 children with intracranial ependymal tumors (33-infratentorial, 18-supratentorial received initial treatment at the University of Pennsylvania. Therapy consisted of total or near total tumor resection in 15 patients and partial resection or biopsy in 36. Postoperative irradiation alone was given to 18, chemotherapy to 4, and a combination of these two modalities to 26. Patients have been followed for a median period of 7.75 years. The 5-year actuarial survival and progression-free survival (PFS) rates are 46% and 30%, respectively. Of the 30 patients who have progressed, 29 did so locally and one died before the site of failure could be determined. Six patients also had disease outside the primary site at relapse; three of them had received craniospinal irradiation. Local control was significantly better for patients whose tumor dose exceeded 4500 cGy (32% vs. 0%, p = .01) and for Caucasian patients (34% vs. 15%, p =.05). Survival was better for patients who were over 4 years of age at diagnosis (55% vs. 30%, p = .04), for patients who received local radiation doses above 4500 cGy (51% vs. 18%, p = .01), and for Caucasian patients (43% vs. 14%, p = .01). Extent of resection, histology, location, the use of cranial or craniospinal irradiation, and the use of chemotherapy did not significantly impact on survival. We conclude that the inability to control local disease remains the single most important factor leading to treatment failure. Older age, higher local radiation dose, and Caucasian race appear to be the only favorable prognostic factors.     

Outcome for children with group III rhabdomyosarcoma treated with or without radiotherapy

PURPOSE: To analyze the sites of relapse, relapse-free survival, and overall survival in children with Group III rhabdomyosarcoma treated with or without radiotherapy (RT). METHODS AND MATERIALS: The outcomes of 48 children with Group III rhabdomyosarcoma treated between 1980 and 1997 were evaluated. The median overall survival follow-up was 7.3 years. Of the 48 patients, 65% had embryonal histology. Local treatment after induction chemotherapy included complete surgical resection (CSR) alone in 9 (19%), CSR plus RT in 13 (27%), partial resection or rebiopsy plus RT in 10 (21%), and RT alone in 15 patients (31%). One child developed distant disease before completing local therapy. RESULTS: Of the 48 patients, 12 developed relapse at local (n = 3), regional (n = 4), or distant (n = 5) sites. All 9 patients treated with CSR after induction chemotherapy had embryonal/botryoid histology. Only 1 of these 9 patients developed relapse. No statistically significant difference was found in overall survival (p = 0.95) or relapse-free survival (p = 0.67) between patients treated with or without RT. The Kaplan-Meier estimate of 5-year overall survival and relapse-free survival was 76% +/- 7% and 74% +/- 7%, respectively. Significant predictors of relapse-free survival on univariate analysis included CSR (p = 0.03), nodal positivity (p = 0.001), and embryonal histology (p = 0.0003). On multivariate analysis, embryonal histology was the most significant predictor of relapse-free (p = 0.001) and overall (p = 0.01) survival. CONCLUSION: The overall survival for children with Group III rhabdomyosarcoma in this series was favorable. Embryonal/botryoid histology was the most significant predictor of both overall and relapse-free survival. We found that for a selected subgroup of children with embryonal histology, induction chemotherapy followed by complete surgical resection alone may be adequate local therapy.     

Radiotherapeutic management of adult intraspinal ependymomas

Twenty-two adults with ependymomas of the spinal cord were treated with surgery and postoperative radiation between January 1963 and December 1983. The median age was 47 years. Nineteen patients had grade 1 lesions, two had grade 2 and one grade 3. Ten patients had the myxopapillary histologic subtype (all grade 1) and 12 had the cellular variant. There were 15 distal cord lesions originating from the conus medullaris, filum terminale and/or cauda equina. The remaining seven lesions arose more proximally. Fourteen patients had localized lesions involving one to three vertebral segments, while the remaining eight had extensive ependymomas spanning six to thirteen vertebral segments. The median time from onset of symptoms to diagnosis was 3 years. Surgical treatment consisted of biopsy only in three patients, subtotal removal in eleven patients and total removal in eight patients. Radiation was given to the spine only in all cases. Five patients received whole spine radiation; seventeen received partial spine treatment, appropriate for the length of the primary lesion. The median dose was 5000 cGy (range 3600-5700 cGy). The disease free survival at 5 and 10 years was 81 and 71%, respectively. Overall survival at 5 and 10 years was 95%. Seven of twenty-two (32%) patients failed. Factors analyzed for prognostic significance included age, sex, histology, extent of primary, location of primary within the cord, extent of surgical resection and dose. Too few grade 2 and 3 patients precluded meaningful statistical analysis of grade as a prognostic factor. Neither age, sex, histology, extent of primary, location of primary, nor extent of surgical removal significantly affected disease free or overall survival (p greater than 0.05). Four of nineteen (21%) patients with grade 1 lesions failed, while all three patients with grade 2 and 3 lesions did so. Half of the eight patients with extensive ependymomas failed compared to three of fourteen (21%) with limited ones. Six of seventeen (35%) patients failed at doses less than or equal to 5000 cGy while only one of five (20%) failed at doses greater than 5000 cGy. Patterns of failure were analyzed for the seven patients who failed. Six of the seven failures (86% of the failure group, 27% of the overall group) were local, that is, within the initial radiation field at the site of the original tumor. A single patient (grade 2) failed in the posterior fossa while remaining NED in the spinal cord (a head CT scan at initial work-up was negative).(ABSTRACT TRUNCATED AT 400 WORDS)     

Carcinoma of the major salivary glands treated by surgery or surgery plus postoperative radiotherapy

From 1975 to 1987, 87 patients with carcinomas of the major salivary glands (70 parotid and 17 submandibular) were treated at our institution by either surgery or surgery followed by postoperative radiotherapy (RT). Surgical procedures included superficial (24%) or total (56%) parotidectomies and submandibular gland resection (20%). Postoperative RT usually began 2 to 4 weeks following surgery. Using 4 MV photons or, infrequently, 60Co, the majority of patients received 6000 cGy in 6 weeks to the parotid region (ranged from 4500 to 7000 cGy). Determinant actuarial survival was 74% at 5 years and 71% at 10 years. For patients with previously untreated disease, 5 of 19 (26%) treated by surgery alone experienced local recurrence, whereas only 2 of 50 (4%) recurred locally following surgery plus postoperative RT (p = 0.01). For patients presenting with recurrent disease, 4/4 (100%) failed locally following surgery as opposed to 3/14 (21%) following surgery plus postoperative RT (p = 0.01). The determinant 5-year actuarial survival for patients receiving postoperative RT was 75% versus 59% for surgery alone. Results were analyzed by multivariate methods using determinant survival or recurrence as endpoints. Five important prognostic factors were identified. (a) Facial nerve paresis was predictive of poor outcome (p less than 0.001) with 3-year relapse free survival of 13%. (b) Undifferentiated histology was associated with decreased survival (p = 0.002). (c) Male sex was associated with poor outcome (p = 0.008). (d) Skin invasion resulted in decreased survival (p = 0.012). (e) Radiotherapy was associated with improved survival (p = 0.014). In addition, postoperative RT was effective in preventing local recurrence (p less than 0.001). The data demonstrate the efficacy of postoperative RT in improving survival and local control for patients with carcinomas of the major salivary glands.     

Failure patterns and survival in pediatric soft tissue sarcoma

We retrospectively analyzed 44 patients with localized soft tissue sarcomas who were seen and treated at the JCRT, DFCI, and TCH between 1970-1984. Patients with rhabdomyosarcoma were excluded. Primary tumors were located in the following sites: extremities 19 (43%), head and neck 9 (20%), and trunk 16 (37%). Median follow-up for survivors was 7.7 years (range 24 mo-16 years). Surgery was the initial aspect of treatment for all patients. All patients also received post-operative irradiation, 43 at presentation and one at local relapse, and 26 received adjuvant chemotherapy. Radiation was delivered to a dose of 4000 cGy (median) followed by a boost to a median dose of 5760 cGy (range 4500-7000 cGy). Actuarial 5- and 10-year disease-free survivals (DFS) were 70% and 59% while the actuarial 5- and 10-year overall survivals (OS) were both 75%. All parameters were assessed for significance by univariate analysis. OS was significantly affected by presenting stage when analyzed according to both the Intergroup Rhabdomyosarcoma Staging System (IRS) and the American Joint Committee on Cancer system (AJCC). For the IRS, OS at 10 years was 100% for Stage I, 72% for Stage II, and 54% for Stage III (p = 0.04). For the AJCC, OS at 10 years was 100% for Stage I and 65% for Stage II and III (p = 0.05). Primary site, histology, and use of adjuvant chemotherapy did not influence OS or DFS. Fourteen patients failed: 8 local, 1 distant, and 5 combined local and distant. There was no LF among the 9 pts. with primary lesions less than 5 cm compared to 11/29 (39%) whose tumor was greater than 5 cm (p = 0.04). Pts. with gross residual disease had a local DFS of 42%, but those with no residual or microscopic residual had a local DFS of 71% (p = 0.02). In conclusion, childhood STS has an excellent OS (75% at 10 years). Tumor size and residual tumor after surgery strongly predicted for local failure. Of interest, the pattern of failure is predominantly local in our series. This suggests that more aggressive local treatment is indicated in management of children with STS. Higher doses of irradiation as used for adult STS are probably indicated for patients with gross residual disease.     

Radical radiation therapy with 5-fluorouracil infusion and mitomycin C for oesophageal squamous carcinoma

Thirty-five patients with clinically staged non-metastatic squamous carcinoma of the oesophagus were treated with radiation combined with mitomycin C, and 5-fluorouracil (5-FUra) infusion. Twenty patients were planned for a split course regimen 2250-2500 cGy in 10 fractions and chemotherapy. This dose of radiation to be repeated with another course of chemotherapy after 4 weeks rest. Fifteen patients were planned for a single course 4500-5000 cGy in 20 fractions and a single course of chemotherapy. Thirty-one patients are available for a minimum follow-up of one year, 26 patients for a minimum follow-up of 2 years. All 35 patients are included in the survival and local relapse-free analysis. Survival at one year is 47% and at 2 years 28%. The local relapse-free rate at both one and 2 years is 48%. There was an improvement in survival and local relapse-free rate for the single course regimen compared to the split course; 2 years survival 48% versus 12% (p = 0.24) local relapse-free rate 79% versus 27% (p = 0.07). All patients receiving radiation and chemotherapy were compared with historical controls treated by radiation alone. This matching procedure was done independent of knowledge of outcome (two controls were matched/case). Patients were matched for age, sex. TNM stage, and total radiation dose. There was a significant difference in survival p = 0.004 and local relapse-free rate p = 0.05 for patients receiving radiation and chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postoperative radiation therapy of rectal cancer

Beginning in December 1975, at the Massachusetts General Hospital (MGH) patients with rectal carcinomas thought to be at high risk of local recurrence after potentially curative surgical resection, were entered on a treatment protocol of high dose postoperative radiation therapy. Treatment was given with X rays of 10 MeV, generally using a four-field box technique to a dose of 4500 cGy with a boost to 5040 cGy or higher when the small bowel could be excluded from the reduced field. One-hundred sixty-five patients who began their radiation therapy between December 1975 and December 1982 were entered into the study. The median age was 65 years. The median follow-up in the survivors was 56 months, with a minimum follow-up of 17 months. All but 10 patients were followed for more than 2 years. Of the entire group, the actuarial 5-year survival was 53%, with survival of 71% in patients with Stage B-2, 39% in Stage C-2, and 17% in Stage C-3. Local failure was seen in 5/53 patients with Stage B-2 disease and 0/7 of patients with Stage B-3 disease. In patients with positive lymph nodes, local failure occurred in 2/10 (20%) of patients with Stage C-1, 16/77 (21%) of Stage C-2, and 8/15 (53%) of patients with Stage C-3 disease. Compared to previous series of surgery alone, the local failure rate has been decreased by more than one-half in all patients, except those with Stage C-3. Efforts to maximize the radiation doses in all stages should be made to minimize local failure. For Stage C-3, newer strategies such as intraoperative radiation therapy should be employed to decrease the continuing high incidence of failures.     

Results of radical radiation therapy in clinical stage I, technically operable non-small cell lung cancer

From 1970 to 1983, 1,646 lung cancer patients were referred for treatment to the Hunter Radiation Therapy Center, Yale-New Haven Hospital. Forty-three patients had clinical Stage I non-small cell lung cancer felt to be surgically resectable but were treated with radical radiation therapy either for medical reasons (37 patients) or because the patient refused surgery (six patients). This group of clinical Stage I lung cancer patients is understaged by modern criteria since the majority of patients did not have thoracic CT scans and staging was based on fairly limited clinical and radiographic studies. The histological diagnosis was squamous cell carcinoma in 53% of the Stage I patients, adenocarcinoma in 25%, and other non-small cell histologies in 22%. All patients were treated with megavoltage irradiation and the mediastinum was treated in 88% of the patients. Eleven patients were treated with a continuous course (CC) and 32 patients received split course (SC) therapy based on physician preference. The CC consisted of a median fraction size of 200 cGy to a total median dose of 5900 cGy in 6-7 weeks. The SC used a median fraction site of 275 cGy to a total median dose of 5400 cGy over a 6-week period with a 2-week rest in the middle of treatment. The actuarial survival rate of the 43 clinical Stage I patients was 36% at 3 years and 21% at 5 years. Intrathoracic failures occurred in 39% of the patients. Despite the fact that the CC group was similar to the SC group in terms of age, histology, and tumor extent, the CC patients had a lower thoracic failure rate (2/11) versus 15/32), a longer median survival (51.6 months versus 27 months), and a better actuarial 5-year survival rate (45% versus 12%) when compared to the SC patients. Using Cox regression analysis to compare survival curves, the CC group had a significantly better survival compared to the SC group (p = .04).     

Long-term results of infusional 5-FU, mitomycin-C and radiation as primary management of esophageal carcinoma.

An analysis of the results of 90 patients with esophageal cancer treated prospectively with combined chemotherapy and radiation without surgery and with a median follow-up of 45 months is presented. Fifty-seven patients with Stage I or II disease received definitive treatment consisting of 6,000 cGy in 6 to 7 weeks and 5-FU (1,000 mg/m2/24 hr) as a continuous intravenous (IV) infusion for 96 hours, starting on days 2 and 29. Mitomycin C (10 mg/m2) was administered as a bolus injection on day 2. Thirty-three patients received palliative treatment (5,000 cGy plus above chemotherapy) for Stage III, IV, or otherwise advanced disease (extraesophageal spread, distant metastases, multiple primary tumors). Follow-up ranged from 1 month to 96 months. Overall median survival of Stage I and II patients was 18 months with 3- and 5-year actuarial survival of 29% and 18%, respectively, while the median disease specific survival was 20 months with an actuarial disease specific survival of 41% and 30% at 3 and 5 years, respectively. A multivariate analysis of sex, histology, tumor location, and tumor size on survival revealed that the effect of stage was highly significant (Stage I versus II, 73% versus 33% at 3 years, p = .01), whereas the effect of sex approached significance (females versus males, 57% versus 34% at 3 years, p = less than .1). The actuarially determined local relapse-free rate for Stage I and II patients at both 3 and 5 years was 70%. Multivariate analysis again indicated stage to be highly significant (Stage I versus II, 100% versus 60% at 3 years, p = less than .01), whereas sex approached significance (female versus male, 75% versus 66% at 3 years, p = .07). The pattern of failure may be altered with this treatment regimen from local to one dominated by distant metastases. Of 29 patients who have failed, 14 (48%) had any component of local failure, whereas 21 (72%) had a distant failure as a component of failure. The median survival of patients with Stage III or IV disease was 9 months and 7 months, respectively. Palliation in this group of patients with advanced disease was good as 77% were rendered free of dysphagia post-treatment, and 60% were without dysphagia until death with a median dysphagia-free duration of 5 months. Severe toxicities were uncommon and nearly all were transient. Eleven of 90 patients (12.2%) had severe acute toxicities, whereas only 3 patients (3.3%) developed significant late treatment-related complications requiring hospitalization for management.     

Phase I/II trial of pre-operative radiation therapy and coloanal anastomosis in distal invasive resectable rectal cancer.

A total of 22 patients with the diagnosis of invasive, resectable, primary adenocarcinoma of the rectum limited to the pelvis were enrolled on a Phase I/II trial of pre-operative radiation therapy+low anterior resection/coloanal anastomosis. By pre-operative assessment, all patients had invasive tumors involving the distal half of the rectum and required an abdominoperineal resection. The median tumor size was 4 cm (1.5-6 cm) and the median distance from the anal verge was 4 cm (3-7 cm). The whole pelvis received 4680 cGy followed by a 360 cGy boost to the primary tumor bed. The median follow-up was 29 months (10-60 months). Of the 21 patients who underwent resection, 10% had a complete pathologic response and 90% were able to successfully undergo a low anterior resection/coloanal anastomosis. The incidence of local failure as a component of failure was crude: 23% and 4-year actuarial: 32%. The 4-year actuarial survival was 61%. No patients experienced Grade 3 or 4 toxicity while receiving radiation therapy, and 6% developed a partial disruption of the anastomosis. Of the patients who underwent a low anterior resection/coloanal anastomosis, 89% had a good or excellent functional result. This technique may be an alternative to an abdominoperineal resection in selected patients. Further follow-up is needed in order to determine if this approach ultimately has similar local control and survival rates as an abdominoperineal resection.     

Impact of tumor control on survival in carcinoma of the lung treated with irradiation

The long-term results in tumor response, intrathoracic tumor control and survival are reported in patients with medically inoperable or unresectable non-oat cell and small cell carcinoma of the lung. In 376 patients with stages T1-3, NO-2 carcinoma of the lung tumors, accessioned to a Radiation Therapy Oncology Group (RTOG) randomized study to evaluate different doses of irradiation, a higher complete response rate (24%), intrathoracic tumor control (67%) and three year survival (15%) was observed with 6000 cGy, compared with lower doses of irradiation (4000 or 5000 cGy). Increased survival was noted in patients with complete tumor response. Three year survival in complete responders was 23%, in partial responders, 10%, and in patients with stable disease, 5%. Patients treated with 6000 cGy had an overall intrathoracic failure rate of 33% at 3 years, compared with 42% for those treated with 5000 cGy, 44% for patients receiving 4000 cGy with split course, and 52% for those treated with 4000 cGy continuous course (p = 0.02). Patients surviving 6 or 12 months exhibited a statistically significant increased survival when the intrathoracic tumor was controlled. Patients treated with 5000-6000 cGy, showing tumor control, had a three year survival of 22%, versus 10%, if they had intrathoracic failure (p = 0.05). In patients treated with 4000 cGy (split or continuous), the respective survival was 20% and 10%, if the intrathoracic tumor was controlled (p = 0.001). In patients surviving 12 months after treatment with 5000-6000 cGy, on whom the intrathoracic tumor was controlled, the median survival was 29 months, in contrast to 18 months, if they developed intrathoracic failure (p = 0.05). In patients treated with 4000 cGy, the median survival was 23 months with control and 18 months without control of the intrathoracic tumor [corrected] (p = 0.008). In another RTOG study for patients with more advanced tumors (T4 or N3), those with local tumor control at 12 months had a three year survival rate of 25%, compared with 5% for those with thoracic failures. These differences are statistically significant (p = 0.006). Higher doses of irradiation yield a greater proportion of complete response, higher intrathoracic tumor control and better survival in non-oat cell medically inoperable or unresectable carcinoma of the lung.(ABSTRACT TRUNCATED AT 400 WORDS)     

Isolated local-regional recurrence of breast cancer following mastectomy: radiotherapeutic management

Two hundred twenty-four patients with their first, isolated local-regional recurrence of breast cancer were irradiated with curative intent. Patients who had previous chest wall or regional lymphatic irradiation were not included in the study. With a median follow-up of 46 months (range 24 to 241 months), the 5- and 10-year survival for the entire group were 43% and 26%, respectively. Overall, 57% of the patients were projected to be loco-regionally controlled at 5 years. The 5-year local-regional tumor control was best for patients with isolated chest wall recurrences (63%), intermediate for nodal recurrences (45%), and poor for concomitant chest wall and nodal recurrences (27%). In patients with solitary chest wall recurrences, large field radiotherapy encompassing the entire chest wall resulted in a 5- and 10-year freedom from chest wall re-recurrence of 75% and 63% in contrast to 36% and 18% with small field irradiation (p = 0.0001). For the group with recurrences completely excised, tumor control was adequate at all doses ranging from 4500 to 7000 cGy. For the recurrences less than 3 cm, 100% were controlled at doses greater than or equal to 6000 cGy versus 76% at lower doses. No dose response could be demonstrated for the larger lesions. The supraclavicular failure rate was 16% without elective radiotherapy versus 6% with elective radiotherapy (p = 0.0489). Prophylactic irradiation of the uninvolved chest wall decreased the subsequent re-recurrence rate (17% versus 27%), but the difference is not statistically significant (p = .32). The incidence of chest wall re-recurrence was 12% with doses greater than or equal to 5000 cGy compared to 27% with no elective radiotherapy, but again was not statistically significant (p = .20). Axillary and internal mammary failures were infrequent, regardless of prophylactic treatment. Although the majority of patients with local and/or regional recurrence of breast cancer will eventually develop distant metastases and succumb to their disease, a significant percentage will live 5 years. Therefore, aggressive radiotherapy should be used to provide optimal local-regional control.(ABSTRACT TRUNCATED AT 400 WORDS)     

Vaginal recurrences of endometrial carcinoma: the prognostic value of staging by a primary vaginal carcinoma system

Fifty-five of 1716 women with endometrial carcinoma seen consecutively at three institutions prior to 1986 were found to have an isolated post-hysterectomy vaginal recurrence. Their therapy included external radiation therapy (RT) and brachytherapy for 26 women, external RT alone for 17, brachytherapy only for 4, and no RT for 8. Combined external RT/brachytherapy doses ranged from 2000 to 10,000 cGy with a median of 6000 cGy. The 3- and 5-year actuarial survival rates are 48% and 31% for the entire group, and the 3- and 5-year pelvic control rates are 52% and 42%. The 5-year survival and pelvic control rates for those who received greater than or equal to 6000 cGy in total RT dose are 47% and 68%, compared with 12% and 10% for those receiving less than 6000 cGy (p = 0.002 and p = 0.004). For patients receiving their second RT course, the 5-year survival rate is 16%, compared with 48% for those not previously irradiated. The Perez modification of the International Federation of Gynecology and Obstetrics (FIGO) staging system for primary vaginal carcinoma was applied to each recurrence. There were 15 Stage I cases (vaginal mucosa), 32 Stage II cases divided between 15 Stage IIA (subvaginal infiltration) and 17 in Stage IIB (parametrial infiltration), and 8 Stage III cases (pelvic wall involvement). The 3-year actuarial survival and pelvic control rates using this staging system are: Stage I: 85%/100%; Stage II: 41%/43%, Stage IIA: 59%/53%, Stage IIB: 26%/35%; Stage III: 13%/0%. These outcome endpoints are significantly better for Stage I than Stage II patients (p = 0.01 & 0.0004) and for Stages I and IIA compared to Stages IIB and III (p = 0.0005 & 0.002). The pre-treatment variables of age, interval since hysterectomy, initial stage, and location did not predict for survival, but a higher rate of pelvic control was observed for apical than for suburethral recurrences (56% vs. 20%). Grade III histology was highly correlated with poor survival (p = 0.0006). This vaginal carcinoma staging system appears to have value in predicting treatment outcome for patients with post-hysterectomy vaginal recurrences.     

The prognostic significance of late local recurrence after breast-conserving therapy

Of 178 local recurrences occurring in 1593 patients with clinical Stages I-II breast cancer treated by conservative surgery and megavoltage radiotherapy, 71 were diagnosed after the 5th year. Compared with recurrences occurring prior to 60 months, late recurrences were less frequently inoperable (1/71, 1.4%, versus 18/107, 17%, p less than 0.001), were more often located at a distance from the initial primary tumor (23/71, 32%, versus 15/106, 14%, p less than 0.005), and had a more favorable prognosis (5-year survival 84% versus 61% for late and early operable recurrences, respectively, p = 0.05). Five-year metastasis-free survival after late failure depended mainly on the anatomic extent of the recurrence (87% for recurrences apparently confined to the breast versus 34% for relapses involving the axilla, p less than 0.002). Prognosis of late recurrence appeared to be unaffected both by location of the recurrence within the breast and by the type of salvage operation used (mastectomy versus wide excision). Local-regional control after salvage surgery was satisfactory (89% at 5 years). Whereas recurrence in the breast prior to 5 years profoundly affected survival after initial diagnosis, patients with late failure had identical 15-year survival as other 5-year survivors who never failed locally. Late recurrences were more frequent in patients younger than 40 at initial treatment, and in patients who had inadequate radiotherapy. We conclude that late local recurrences after breast conservation do not represent a serious management problem.     

Conformal Radiation Therapy as Definitive Treatment of Stage I Non—Small-Cell Lung Cancer: University of California San Diego Experience

PurposeSurgical resection remains the treatment of choice for patients with stage I non—small-cell lung cancer (NSCLC). However, there is high likelihood of medical comorbidity in this patient population, requiring management by nonsurgical approaches. We report our experience using conventional and hypofractionated radiation therapy schedules with conformal approach.Patients and MethodsBetween 1991 and 2006, 108 patients with medically or otherwise inoperable stage T1/T2 N0 NSCLC were treated with curative radiation therapy alone at our institution. Patient characteristics were as follows: median age, 73 years (range, 37–86 years); male, 88/108 (81.5%); stage T2, 46/108 (42.6%), and histology/cytology, 91/108 (84.3%). Patients received a median total dose of 6500 cGy using median daily dose fractions of 250 cGy. The majority of patients were treated using hypofractionated schedules: daily dose fractions > 200 cGy, 79/108 (73.1%). The following outcomes were analyzed: local failure-free survival (LFFS; time to local failure or death from any cause), time to local or distal failure as first event, and overall survival (OS). Local failure was defined as an increase in size on imaging studies. Toxicities were evaluated using Common Terminology Criteria for Adverse Events v3.0.ResultsMedian follow-up was 19.9 months (range, 4–138.9 months). Median LFFS was 20.8 months (95% CI, 15.1–24.3 months), and median OS was 20.9 months (95% CI, 17.1–27.2 months). Analysis of competing risks showed that, at 5 years, the probability of local failure as the first detected event was 17.1% (95% CI, 10.3–25.3%), the probability of distal failure as the first detected event was 17.9% (95% CI, 11–26.1%), and the probability of death without recording a failure was 50.7% (95% CI, 40.1–60.3%). Patients aged ≥ 70 years had higher probability of death without recording a failure within 5 years (55.5%; 95% CI, 41.7% −67.3%) than patients aged < 70 years (42.6%; 95% CI, 36.4%–58%) but similar probability of local failure as first detected event (age ≥ 70 years, 14.9%; 95% CI, 7.1%–25.1%; age < 70 years, 19.9%, 95% CI 8.9% −33.9%). There was no significant difference in LFFS when comparing tertiles of dose per fractionation or presence or absence of histology/cytology at diagnosis. No patients experienced grade ≥ 4 toxicity, and only 4 patients had grade 3 toxicity.ConclusionConformal radiation therapy is an effective and safe alternative to surgery for patients with stage I NSCLC. The results are limited because this is a single-institution observational study. Nevertheless, a large majority of patients remained free of local recurrence and without significant clinical toxicity.     

Combined modality therapy of extrahepatic biliary system cancer

From January 1985 to December 1988, 10 patients with local/regional extrahepatic biliary system cancer (gallbladder: 2, Klatskin: 4, common bile duct: 4) underwent combined modality therapy. Laparotomy and biopsy or subtotal resection were performed in six patients and endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiogram, and biliary drainage in four patients. Patients initially received 5000 cGy to the tumor bed and primary nodal area. Eight received an additional 1500 cGy boost to the tumor bed. Chemotherapy (5-FU/mitomycin-C) was delivered at the beginning of each radiation treatment course. Four patients received an additional 1-4 cycles of maintenance chemotherapy and six received a boost with brachytherapy. The mean survival was 32 months and the median survival was 16 months. Five patients are currently NED at 16, 17, 17, 48, and 52 months. The overall 3-year actuarial survival was 50%. The cumulative incidence of failure as a component of failure was local/regional: 50%, abdominal: 40%, and distant: 10%. Of the five patients who developed failure, all developed a component of local/regional failure. Our data show that this approach is feasible and offers similar results to those reported in the literature. However, further follow-up will be needed to determine if this combined modality approach offers improved local control and survival rates compared with surgery or biliary bypass/drainage alone.     

Treatment of penile carcinoma: To cut or not to cut?

PURPOSE: The aim of this study was to assess the outcome in patients with penile cancer. METHODS AND MATERIALS: A total of 60 patients with penile carcinoma were included. Of the patients, 45 (n = 27) underwent surgery, and 51 underwent definitive (n = 29) or postoperative (n = 22) radiotherapy (RT). Median follow-up was 62 months. RESULTS: Median time to locoregional relapse was 14 months. Local failure was observed in 3 of 23 patients (13%) treated with surgery with or without postoperative RT vs. in 19 of 33 patients (56%) given organ-sparing treatment (p = 0.0008). Of 22 local failures, 16 (73%) were salvaged with surgery. Of the 33 patients treated with definitive RT (n = 29) and the 4 patients refusing RT after excisional biopsy, local control was obtained with organ preservation in 13 (39%). In the remaining 20, 4 patients with local failure underwent salvage conservatively, resulting in an ultimate penis preservation rate of 17 of 33 (52%) patients treated with definitive RT. The 5-year and 10-year probability of surviving with an intact penis was 43% and 26%, respectively. There was no survival difference between the patients treated with definitive RT and primary surgery (56% vs. 53%; p = 0.16). In multivariate analysis, independent factors influencing survival were N-classification and pathologic grade. Surgery was the only independent predictor for better local control. CONCLUSION: Based on our study findings, in patients with penile cancer, local control is superior with surgery. However, there is no difference in survival between patients treated with surgery and those treated with definitive RT, with 52% organ preservation.     

Dynamic pion irradiation of unresectable soft tissue sarcomas

Since November 1981, when pion irradiation was introduced for deep seated tumors at the Swiss Institute for Nuclear Research (SIN, now Paul Scherrer Institute, PSI) a dynamic, 3-dimensional spot scan treatment technique has been in use. To exploit this technique a special optimization treatment planning system has been designed. Of a total of 331 patients treated with pions from November 1981-December 1987, 35 were irradiated for unresectable soft tissue sarcomas. In 32/35 patients, tumor sites were retroperitoneal, pelvic or in the groin or thigh. Twenty-nine tumors had a maximum diameter of greater than 10 cm, 18 tumors of greater than 15 cm; 30 tumors had grade 2/3 and 32 Stage III B/IV A/IV B. Eight of 35 patients received a low pion total dose, 7-27 Gy. Twenty-seven patients received a total dose of 30-36 Gy, fraction size 150-170 cGy (90%-isodose), 20 fractions, 4 times per week. Of these 27 patients, severe late reactions appeared in five: 2/8 patients with extremity/groin sarcomas (1/2 caused by biopsy) and 3/19 patients with retroperitoneal/pelvic sarcomas (one a skin reaction after Actinomycin-D, one a small bowel reaction after 36 Gy, a dose no longer used). Seven of 27 patients had metastases at the beginning of irradiation. Three of 27 were treated with excisional biopsy, 9 with incisional biopsy or partial resection and in 15 patients biopsies were performed for histology only. The median follow-up of these 27 patients was 17 months (5-66). There was no progression in eight extremity/groin tumors but in 4 of 19 retroperitoneal/pelvic tumors. Three of these were marginal progressions. The actuarial 5-year rate of local tumor control is 64%; the actuarial 5-year survival rate of patients without metastases at the beginning of treatment is 58%. Dynamic spot scan pion irradiation proves to be a successful treatment technique for unresectable sarcomas with a high rate of tumor control and a very low rate of severe late reactions.     

Penile brachytherapy: results for 49 patients

PURPOSE: To report results for 49 men with squamous cell carcinoma (SCC) of the penis treated with primary penile interstitial brachytherapy at one of two institutions: the Ottawa Regional Cancer Center, Ottawa, and the Princess Margaret Hospital, Toronto, Ontario, Canada. METHODS AND MATERIALS: From September 1989 to September 2003, 49 men (mean age, 58 years; range, 22-93 years) had brachytherapy for penile SCC. Fifty-one percent of tumors were T1, 33% T2, and 8% T3; 4% were in situ and 4% Tx. Grade was well differentiated in 31%, moderate in 45%, and poor in 2%; grade was unspecified for 20%. One tumor was verrucous. All tumors in Toronto had pulsed dose rate (PDR) brachytherapy (n = 23), whereas those in Ottawa had either Iridium wire (n = 22) or seeds (n = 4). Four patients had a single plane implant with a plastic tube technique, and all others had a volume implant with predrilled acrylic templates and two or three parallel planes of needles (median, six needles). Mean needle spacing was 13.5 mm (range, 10-18 mm), mean dose rate was 65 cGy/h (range, 33-160 cGy/h), and mean duration was 98.8 h (range, 36-188 h). Dose rates for PDR brachytherapy were 50-61.2 cGy/h, with no correction in total dose, which was 60 Gy in all cases. RESULTS: Median follow-up was 33.4 months (range, 4-140 months). At 5 years, actuarial overall survival was 78.3% and cause-specific survival 90.0%. Four men died of penile cancer, and 6 died of other causes with no evidence of recurrence. The cumulative incidence rate for never having experienced any type of failure at 5 years was 64.4% and for local failure was 85.3%. All 5 patients with local failure were successfully salvaged by surgery; 2 other men required penectomy for necrosis. The soft tissue necrosis rate was 16% and the urethral stenosis rate 12%. Of 8 men with regional failure, 5 were salvaged by lymph node dissection with or without external radiation. All 4 men with distant failure died of disease. Of 49 men, 42 had an intact and tumor-free penis at last follow-up or death. The actuarial penile preservation rate at 5 years was 86.5%. CONCLUSIONS: Brachytherapy is an effective treatment for T1, T2, and selected T3 SCC of the penis. Close follow-up is mandatory because local failures and many regional failures can be salvaged by surgery.     

The significance of radiotherapy treatment duration in intracranial ependymoma

PURPOSE: To determine if radiation therapy treatment duration has an impact on the outcome of intracranial ependymoma. METHODS AND MATERIALS: From 1965 to 1997, 34 patients with intracranial ependymoma were seen and treated with postoperative radiotherapy (RT). There were 26 male and 8 female patients with a median age of 14 years (range, 18 months to 60 years). Tumor location was infratentorial in 23 (67.6%) and supratentorial in 11 (32.4%). Pathology was low-grade in 25 (73.5%) and high-grade in 9 (26.5%). Two (5.9%) patients had M+ disease at initial diagnosis. Gross total resection was achieved in 12 (35.3%), subtotal resection in 19 (55. 9%), and biopsy alone in 3 (8.8%). Median RT dose to the primary site was 5400 cGy (range, 4500 cGy to 6600 cGy). The entire neuraxis was treated in 14 (41.2%), whole brain in 9 (26.5%), and the primary site alone in 11 (32.4%). Median radiotherapy treatment duration was 43 days (range, 26 to 122 days). Patients treated with craniospinal RT were more likely to have treatment duration of > or =50 days. Median follow-up was 108 months (range, 24 to 252 months). RESULTS: The 5-, 10-, and 15-year overall survival rates were 71.5%, 63.3%, and 55.4%. Local control rates at 5, 10, and 15 years were 61.8%, 57.7%, and 57.7%. For patients with RT treatment duration <50 days, the 5-, 10-, and 15-year overall survivals were 85.5%, 78.9%, and 65.7% whereas for those with treatment duration > or = 50 days, the corresponding rates were 45.5%, 36.4%, and 36.4% (p = 0.01, log-rank test). Local control rate at 5, 10, and 15 years was 70.6% for patients with RT treatment duration <50 days and 45.5%, 36.4%, and 36.4% for patients with RT treatment duration > or =50 days (p = 0.05, log-rank test). Age, gender, tumor location, tumor grade, degree of surgical resection, RT volume, and RT dose (4500-5399 cGy vs. 5400-6600 cGy) were not found to have a statistically significant impact on overall survival, disease-free survival, or local control. The most common site of failure was local, found in 13 (38.2%) patients. Three patients also had spinal failure in addition to a primary site failure. There were no isolated nonprimary site brain or spine failures. CONCLUSIONS: Radiation therapy treatment duration is an important prognostic factor for survival and local control with patients having treatment duration <50 days having a better outcome than those with treatment duration > or =50 days. Because the overwhelming site of failure was local, we recommend local field irradiation in patients with M0 disease.