Comparison of split-course radiation therapy and continuous radiation therapy for unresectable bronchogenic carcinoma: 5 year results.

One hundred and eighty-eight patients with inoperable or unresectable bronchogenic carcinoma were stratified by cell type, TNM staging, and prior surgery and then randomized into two treatment groups: continuous radiation therapy and split-course radiation therapy. There was no difference in clinical or objective improvement in the two groups. Survival rates for cases of squamous cell carcinoma, small cell carcinoma, and adrenocarcinoma were the same after both regimens of therapy. Split-course therapy resulted in a significantly better survival rate in cases of large cell carcinoma but the number of cases was small. We doubt that the difference is clinically significant. Objective roentgenographic response was accompanied by improved survival in squamous cell carcinoma, but not in the other three cell types. Split-course radiation therapy is superior to continuous radiation therapy because it is better tolerated by the patient and because re-examination of the patient prior to the second half of split-course therapy permits the detection of new metastatic disease that has become manifest during the rest period and spares the patient the futile second half of radiation therapy.     

Prognostic factors and results after the combined surgical and radiotherapy treatment of ependymomas]

Between 1978 and 1991, 31 patients with primary (n = 28) and recurrent (n = 3) ependymoma received external radiation after initial surgery. There were 26 cases of intracranial and five cases of spinal ependymoma. Histological grading revealed low-grade in 23 and high-grade tumors in eight patients. Craniospinal irradiation was given to 13 of 28 patients, whole cranial radiation with boost to posterior fossa in three and local treatment to twelve patients. Six of 28 patients received chemotherapy. Dose to the primary, tumor localisation, grading and extend of surgery did not significantly impact on survival and relapse-free survival. Age was a marginally significant prognostic factor for survival. In patients with intracranial ependymoma (n = 24) survival and relapse-free survival at five years were 54% and 42%, respectively. Patterns of recurrence showed a local recurrence alone in eight, a CNS-relapse with local recurrence in four and local recurrence with distant metastases in one case. Spinal seeding occurred in two of 13 after craniospinal irradiation and two of twelve patients after local treatment. The main problem in the treatment of ependymoma remains local control, the use of spinal irradiation does not seem to improve treatment results.     

Experiences with sole radiation therapy of primary osteogenic sarcomas (author's transl)]

In the course of the previous six years, nine osteogenic and three juxtacortical sarcomas have been irradiated for the single purpose of local tumor sanitation and final cure of the patient. Of nine cases with osteosarcomas, six are still alive. Two are surviving without recurrences these five years, three without metastasition. The 3-year survival amounts to 3/5. Radiation effects from high-dosage treatment are remarkably small. The cure rate after radiation therapy seems not to be inferior to the results after surgery.     

Advanced head and neck cancer: low-dose, split-course radiation therapy and simultaneous infusion of 5-fluorouracil and cisplatin

Twenty-three patients with advanced untreated head and neck cancer, nine patients with recurrent cancer, and six patients with recurrent cancer who underwent surgery and had postoperative persistence of tumor were treated with three 2-week courses of irradiation (1,500 cGy in 10 fractions each) concurrently with cisplatin and a 5-day infusion of 5-fluorouracil. A fourth 2-week course of irradiation (2,000 cGy in 10 fractions) brought the final tumor dose to 6,500 cGy. Twenty patients in the untreated group and three patients in the recurrent group (33%) had a complete response. There were 10 local recurrences in the untreated group (43%), seven in the recurrent group (78%), and three in the persistent group (50%). At 17 months after the start of treatment, the survival rate for the untreated patients was 51%, for the patients in the recurrent group it was 11%, and for the patients in the persistent group it was 20% (P = .03). Most patients experienced toxicity, including nausea, vomiting, weight loss, and mucositis. Clinical trials are necessary to determine whether simultaneous chemotherapy and radiation therapy is an improved method of treatment for advanced head and neck cancer.     

CT of irradiated solid tumor metastases to the brain

Summary Twenty patients with solid tumor metastases to the brain, demonstrated by CT scanning, had follow-up scans after radiation therapy of the metastatic focus. Nine patients (45%) showed no evidence of the metastasis on the initial follow-up scans. Another 10 patients (50%) showed some improvement in the size, enhancement, or surrounding edema of the lesion. Only one patient showed progression in spite of therapy. The CT scan identified those patients who achieved longer survival and/or longer time intervals before brain relapse. However, CT scans must be interpreted with caution in patients still on corticosteroid treatment. Additionally, other non-tumoral conditions may mimic tumor recurrence. Radiation therapy offered palliation in patients with brain metastases, and in some instances, sterilized patients of their metastatic brain involvement.     

Cancer of the piriform sinus: treatment by radiation therapy alone and with surgery

To ascertain the optimal treatment for carcinoma of the piriform sinus, the authors determined survival rates and local and regional tumor growth for two groups of patients: those treated by radiation therapy alone (n = 209) and those treated by radiation therapy combined with surgery (n = 154). The two groups were similar with respect to the characteristics of primary tumor stage and degree of nodal involvement. The overall 3-year and 5-year actuarial survival rates were 19.2% and 15.5%, respectively. For 5-year actuarial survival, there was no significant difference between patients with T1 and T2 tumors, but there was a significant difference between patients with T1 + T2 tumors versus those with T3 tumor. There was no significant difference in 3- and 5-year survival between patients with N0 and N1 nodal involvement and those with N1 and N2 involvement, but there was a significant difference between patients with N0 versus those with N3 involvement. The 5-year actuarial survival rate is significantly better for patients who underwent surgery followed by radiation therapy than for those who received only radiation therapy. However, for patients with early-stage (T1 and T2) tumors, radiation therapy alone controls local tumor growth as well as the combination of surgery and radiation therapy does. For each treatment group, the causes of death and patterns of failure were studied and compared with investigations to date.     

Stage I and II breast carcinoma: treatment with limited surgery and radiation therapy versus mastectomy

Between 1980 and 1986, 2,140 patients with surgical stage I or II breast carcinoma were treated including 1,179 patients with T1-2N0 disease and 961 patients with T1-2N1 disease. Among the 1,179 patients without node involvement, 215 underwent limited surgery (complete excision and axillary node dissection) and radiation therapy; 964 patients underwent modified radical mastectomy only. Of the 961 patients with node involvement, 106 were treated by means of limited surgery and radiation therapy; of these, 48 also received chemotherapy. The remaining 855 patients underwent mastectomy; of these, 381 also received chemotherapy and/or hormone therapy. The 5-year survival rates for patients with no node involvement were 96% for the group treated by means of limited surgery and radiation therapy and 88% for the group treated by means of mastectomy (P greater than .05). The 5-year survival rates for patients with node involvement were 96% for the group treated by means of limited surgery and radiation therapy with or without chemotherapy and 77% for the group treated by means of mastectomy with or without chemotherapy (P less than .01). This study demonstrates no disadvantage from treatment by means of limited surgery and radiation therapy and suggests that adjuvant radiation therapy may be important in increasing survival among patients with T1-2 breast carcinoma and positive axillary nodes.     

High-dose-rate interstitial brachytherapy for vaginal endometrial cancer recurrence after prior surgery and radiotherapy

PurposeCharacterize the clinical outcomes of endometrial cancer vaginal recurrences after previous surgery and radiation therapy treated with reirradiation including image-guided interstitial high-dose-rate (HDR) brachytherapy.Methods and materialsA single-institution retrospective study identifying women receiving reirradiation for vaginal recurrence of endometrial cancer between 2004 and 2017.ResultsTwenty-three women had vaginal recurrences of endometrial cancer, median 13.7 months (range 3.5–104.9) from initial radiation. All received reirradiation with interstitial HDR brachytherapy, and seven also received external beam radiation. Median reirradiation EQD2_10 was 48 Gy (range 24.0–68.81), and median cumulative EQD2_10 was 106.25 Gy (range 62.26–122.0). Median follow-up after reirradiation was 40.2 months (range 4.5–112.7). At 3 years, overall survival was 56%, cancer-specific survival was 61%, and disease-free survival was 46%. 14 patients experienced disease recurrence; 10 including distant sites, one at a regional node only. Three patients experienced local recurrences, two of whom did not complete the prescribed course of reirradiation. The overall crude local control rate was 87%. Three patients experienced Grade 3 vaginal toxicity. There was no bladder or rectal toxicity with Grade >2.ConclusionsReirradiation including interstitial HDR brachytherapy is a promising option for vaginal recurrences of endometrial cancer after prior radiation, with high rate of local control and acceptable toxicity. However, distant failure is common. Further studies are needed to determine cumulative radiation dose limits and the role of systemic therapy in this scenario.     

Advanced head and neck cancer: response to and toxicity of multimodality therapy

This pilot study for resectable stage III and stage IV squamous cell carcinoma of the head and neck used a cytoreduction phase of preoperative radiation with cisplatin, followed by an eradicative treatment phase with radical surgery (group 1) or radical dose radiation and cisplatin (group 2), followed by adjuvant chemotherapy with 5-fluorouracil infusion and cisplatin delivered at 4-week intervals for six cycles following initial radiation therapy to the primary site. A total of 43 patients were treated between January 1984 and January 1987; 14 were classified with stage III carcinoma, 28 with stage IV, and one patient was not staged. Out of 43 patients, two did not complete therapy. Forty-one patients completed the eradicative phase of treatment. Complete tumor clearance at the end of the eradicative treatment phase was 88% (36 of 41 patients), 95% (18 of 19) in group 1 and 82% (18 of 22) in group 2. Actuarial recurrence-free survival was 61% at 3 years. Among 36 patients with complete tumor clearance after the eradicative treatment phase, there was no statistically significant difference for overall and recurrence-free survival between group 1 and group 2. In general, toxicity was not excessive, although mucositis, weight loss, and hematologic and neurologic toxicity were observed in varying degrees in these patients.     

Resectable esophageal carcinoma: local control with neoadjuvant chemotherapy and radiation therapy.

PURPOSE: To evaluate the usefulness of neoadjuvant chemotherapy and radiation therapy before esophagectomy for invasive cancer of the esophagus or gastroesophageal junction (GEJ). MATERIALS AND METHODS: The authors conducted a retrospective analysis of 154 patients who underwent esophagectomy for invasive cancer between September 1, 1991, and December 31, 1995. The end points evaluated were overall, disease-free, local-regional relapse-free, and systemic relapse-free survival. RESULTS: Seventy of the 154 patients received neoadjuvant combined-modality therapy (CMT) consisting of concurrent cisplatin and fluorouracil administration and accelerated, hyperfractionated radiation therapy. The remaining 84 patients underwent immediate esophagectomy. With a median follow-up of 34.7 months, the 3-year overall, disease-free, and distant metastatic relapse-free survival rates were 38.0%, 41.9%, and 56.0%, respectively. Although neoadjuvant therapy did not appear to prevent distant metastases, there was a dramatic effect on local control. After CMT, the 5-year local control rate was 90% compared to 64% after surgery (P < .001). Tumors in the GEJ recurred more frequently (P = .01); however, multivariate analysis showed CMT was the only independent predictor of local control. Postoperative mortality was 15.7% after CMT versus 5.9% without CMT (P = .05). CONCLUSION: Local control of esophageal cancer is excellent following neoadjuvant chemotherapy and radiation therapy. However, the effects of CMT on overall and disease-free survival are less clear due to significant differences between the treatment groups.     

Sarcoma after radiation therapy: retrospective multiinstitutional study of 80 histologically confirmed cases. Radiation Therapist and Pathologist Groups of the Fédération Nationale des Centres de Lutte Contre le Cancer

PURPOSE: To evaluate the best strategy for treatment of sarcoma that occurs after radiation therapy. MATERIALS AND METHODS: Records were retrospectively reviewed for 80 patients with a confirmed histologic diagnosis of sarcoma that occurred after radiation therapy performed during 1975-1995. The patients were treated for breast cancer (n = 33, 42%), non-Hodgkin lymphoma (n = 9, 11%), cervical cancer (n = 9, 11%), benign lesions (n = 4, 5%), or other tumors (n = 25, 31%). Sarcoma occurred after a mean latency of 12 years (range, 3-64 years), with most (70%) developing in the soft tissue. Treatment included surgery (28 patients), surgery and chemotherapy (18 patients), chemotherapy only (15 patients), and radiation therapy (14 patients). RESULTS: By the end of the study, 51 patients were dead, including 46 due to sarcoma. Median survival was 23 months. Overall survival rates at 2 and 5 years, respectively, were 69% and 39% for patients treated with surgery, 10% and 0% for those treated with chemotherapy, and 52% and 35% for those treated with surgery and chemotherapy (P =.001). The 2- and 5-year rates for survival without recurrence were 54% and 32%, respectively. CONCLUSION: The results confirm the beneficial effect of surgery. Further study is needed to explore the roles of combined treatments.     

Non-small cell lung cancer: prognostic factors in patients treated with surgery and postoperative radiation therapy

PURPOSE: To determine survival outcomes, to identify adverse prognostic factors for relapse, and to compare American Joint Commission on Cancer (AJCC) staging systems in patients with non-small cell lung cancer (NSCLC) treated with surgery and postoperative radiation therapy. MATERIALS AND METHODS: Between 1980 and 1995, 211 patients with NSCLC underwent surgery and postoperative radiation therapy. Surgery consisted of wedge resection (12.5%), lobectomy (67.8%), or pneumonectomy (19.7%). Pathologic stages (1992 AJCC) included I (n = 22), II (n = 70), IIIA (n = 104), and IIIB (n = 12). Indications for radiation therapy included compromised margins (n = 81) and/or positive mediastinal nodes (n = 55). Prognostic factors were identified by using univariate and multivariate models. RESULTS: Overall 3-year survival for patients with stage I, II, and IIIA cancer was 58.9%, 44.1%, and 43.2%, respectively. Older age (P = .008), male sex (P = .021), large primary tumor (P = .004), and multiple positive mediastinal nodes (P = .046) were associated with worse rates of survival. Actuarial risk of local-regional relapse (36 patients) was 21.4% at 3 years. In a multivariate model, use of wedge resection (P = .001), positive margins (P = .010), and larger pathologic tumor (P = .059) were risk factors for local-regional recurrence. Actuarial rate of distant failure was 55.2% at 3 years. CONCLUSION: Local-regional control can be achieved with surgery and radiation therapy in approximately 80% of patients; however, the rate of distant metastasis remains unacceptably high. Other variables, such as multiple positive nodes, may serve to identify patients at higher risk for relapse and poorer survival. Methods for improving treatment outcomes in these patients should be pursued.     

Giant cell tumors of bone: treatment with radiation therapy

Records of 15 patients with giant cell tumor of bone treated with radiation therapy over a 35-year period were reviewed; ten patients for whom follow-up information was available constituted the study group. One patient was treated by means of orthovoltage equipment only, a second, by both orthovoltage and megavoltage equipment (cobalt 60). The remaining eight were all treated with megavoltage to doses of 40-52 Gy in 24-30 fractions. Seven patients are alive without disease, with an average survival of 192 months (range, 48-360 months). Three patients died of uncontrolled local and distant disease (average survival, 52 months; range, 23-99 months): one with metastasis in the lungs at time of treatment and two after treatment. Although incidence of lung metastasis appears high, it may be due to patient selection because chemotherapy had failed in all three. Complications from irradiation in one surviving patient required surgical closure of a dural fistula 19 years after treatment. No radiation-induced sarcomatous transformations of controlled tumors were noted. These data suggest that giant cell tumor of bone can be well controlled by radiation therapy. Megavoltage irradiation should be considered in treating local disease not easily controlled by surgery in the axial skeleton. Complications are minimal, and normal function can be preserved in the treated areas.     

Paraocular lymphoid tumors

Forty-two patients with paraocular lymphoid tumors were treated with radiation. Histologically, 20 tumors were classified as benign lymphoid hyperplasia (BLH), ten as indeterminate histology (IH), and 12 as malignant lymphoma (ML). Of the patients with an initial diagnosis of BLH or IH, disseminated ML developed in 23%. Cytologic and histologic studies were not helpful in predicting the malignant potential in some of these tumors. The possibility that BLH represents a premalignant condition with subsequent transformation into ML is discussed. A total of 45 eyes were irradiated in these 42 patients. Initial local control rate was 93%, with ultimate control rate of 100% after retreatment with radiation or surgery. Radiation therapy is the treatment of choice for these tumors; local control rates are high, and morbidity is minimal with proper radiation treatment planning.     

Radiotherapy of malignant gliomas: results from conventional treatment methods and the prospects of advanced techniques

PURPOSE: The results of post-operative radiation therapy of malignant gliomas are disappointing, with mean survival time (MST) of 16-70 weeks and 2-year survival rates ranging from 8.5% to 25% in the literature. A slightly more favourable prognosis is found in the following cases: in anaplastic astrocytomas with respect to glioblastoma multiforme; in younger patients with respect to the more elderly; the longer the duration of symptoms before diagnosis; and in the event in which surgery has been macroscopically radical. An improvement in treatment outcome is foreseeable with the use of advanced volume definition techniques for radiation therapy. MATERIALS AND METHODS AND RESULTS: Our experience with conventional radiation treatment shows therapeutic results in agreement with other institutions. In the overall 134 cases MST was 50 weeks and the 2-year survival rate was 10%. In patients affected by anaplastic astrocytoma MST was 58% and 2-year survival rate was 17%, whereas the figures for glioblastoma multiforme were 47 weeks and 8% (p>0.05, not statistically significant, probably due to the small number of cases). Patients of sixty years of age or less showed a more statistically favourable prognosis: MST was 59 weeks and 2-year survival rate was 16%, compared with 44 weeks and 4% in patients above 60 years of age (p<0.05). The duration of symptoms of 6 months or less had a less favourable prognosis with respect to symptom onset of greater than 6 months: in the former MST was 49 weeks and 2-year survival was 7%, and in the latter the figures were 68 weeks and 40% (P<0.05). Lastly, the presence of residual neoplastic tissue after surgery is an unfavourable element: in this case MST was 41 weeks and 2-year survival was 7%, compared with 68 weeks and 13% (P<0.05) after macroscopically radical surgery. DISCUSSION AND CONCLUSIONS: Computed tomography (CT) is still today an indispensable technique for radiation therapy planning. Magnetic Resonance (MR) imaging, nonetheless, provides greater definition of the neoplastic extension. The possibility of combining CT and MR neuroimaging data together with stereotactic radiotherapy techniques enables the optimal development of the three-dimensional treatment plane. This translates into high dose delivery to the neoplastic volumes without affecting the regions of the brain with no tumour involvement. Furthermore, a real improvement in the prognosis of malignant gliomas must also consider the results from research in the fields of tumour biology and functional neuroimaging.     

Treatment options in high-grade brain tumors: brain brachytherapy.

The extremely poor prognosis of high-grade brain tumors (glioblastoma multiforme and anaplastic astrocytomas) has been well documented in the literature. Almost 90% of patients die within 18 months after therapy, most commonly because of local persistence of the tumor, which may be controlled if a sufficient amount of irradiation can be delivered. Currently, postoperative radiation therapy offers the best median survival rate. However, the response to external-beam radiation therapy has reached a plateau because of the intolerance of healthy brain tissue to excessive irradiation. To treat these tumors, brachytherapy (interstitial implantation of radioactive sources) can be used with debulking surgery. This therapy is becoming an effective alternative to conventional external-beam radiation therapy, since it allows a higher dose to be delivered to the tumor bed without damaging the surrounding healthy brain tissue. With continual refinements of the technique, brachytherapy, performed by a skilled brachytherapy team, offers an opportunity to improve patient survival.     

Ovarian carcinoma: results of radiation therapy and chemotherapy in 83 patients

Eighty-three patients with ovarian cancer who had undergone radiation therapy, chemotherapy, or both were evaluated. Eight patients had FIGO stage I, 12 had stage II, 61 had stage III, and two had stage IV disease. In 60 patients, radiation was delivered with open abdominopelvic field (30 Gy over 4 weeks), with or without a pelvic boost dose. Fifty-five patients received a combination of chemotherapeutic agents, and 30 received a single agent as initial therapy. The patients were divided into three groups. The 26 patients in group 1 received primary radiation therapy with or without adjuvant single-agent chemotherapy. The 34 patients in group 2 underwent radiation therapy after chemotherapy failed. The 23 patients in group 3 received combination chemotherapy. Nineteen patients (23%) achieved complete remission--eight from group 1, two from group 2, and nine from group 3. The 5-year actuarial survival for group 1 was 41% but was only 16% for both groups 2 and 3 combined (P = .026). Primary radiation therapy, with or without adjuvant single-agent chemotherapy, was superior to combination chemotherapy in patients with ovarian cancer.     

Postoperative radiotherapy in the treatment of breast tumors. Evaluation of a 5-year case series

Between January 1981 and December 1985, 364 female patients underwent surgical treatment for breast cancer in Mestre General Hospital. The pathological stage of the disease was stage I in 60 patients, stage II in 215 patients, stage III A in 30 patients, stage III B in 44 patients and stage IV in 15 patients. The patients with T1-T2 N0 lesions located in the outer quadrants received no additional treatment after surgery, while the others received adjuvant therapy. The patients with stage-IV disease (M+) were treated with chemo and/or hormonotherapy. All patients were followed for an average of 33 months up to December 1986 (range 1-71 months). Local-regional relapses developed in 17 patients, 15 on the chest wall and 2 in the drainage lymph nodes (only 7 within the previously-treated area). A 5-year actuarial survival rate was observed of about 78%, and 66% of relapse-free survival, in the whole group of patients (100% and 92% in stage I; 92.5% and 76% in stage II; 51% and 33% in stage III A; 32% and 19% in stage III B; 31% in stage IV, respectively). As far as our series of patients is concerned, the massive involvement of axillary lymph nodes seems to be the most adverse prognostic factor in survival rates. Even though the short follow-up does not allow definitive conclusions to be drawn, the authors believe such loco-regional treatments as surgery and radiation therapy to be extremely important in the local control of breast cancers, as well as in the patients' survival in the long run.     

Postoperative radiation therapy in the management of lung cancer

Postoperative radiation therapy for lung cancer is still controversial. In a 9-year period, 69 patients with non-oat-cell carcinoma of the lung (16% stage I, 26% stage II, and 58% stage III) received such therapy. The radiation dose was less than 5,000 cGy in 42 patients, 5,000-5,900 cGy in 16, and 6,000 cGy or more in 11; follow-up ranged from 24 to 64 months. Actuarial survival at 2 and 4 years was 50% and 16%, respectively, for squamous cell carcinoma, and 40% and 26% for adenocarcinoma. The 5-year survival for stages I, II, and III cancer was 29%, 17%, and 19%, respectively. Histologic findings and type of surgery did not affect survival, but the radiation dose apparently did. The 3-year survival for patients who received less than 6,000 cGy was 35%, compared with 73% for patients who received higher doses. In eight patients, treatment failed within the irradiated volume: all had received doses of less than 6,000 cGy, and the volume in three was judged to be inadequate.     

Postoperative radiation therapy for carcinoma of the uterine cervix

Postoperative radiation therapy (PORT) for cervical cancer has been empirically performed for patients with pathologic risk factors for recurrence after surgery. The efficacy of PORT is mainly supported by retrospective studies. Despite convincing evidence demonstrating a reduction in pelvic recurrence rates when PORT is employed, there is no evidence that it eventually improves patient survival. Local recurrence, such as vaginal stump recurrence, is not always fatal if diagnosed earlier. Some patients, unfortunately, may develop distant metastases even after PORT. The positive effects of PORT also may be counterbalanced by increased toxicities that result from combining local therapies. These factors obscure the efficacy of PORT for cervical cancer patients. There has been no consensus on the predictive value of risk factors for recurrence, which renders indication of PORT for early-stage cervical cancer quite variable among institutions. Today, efforts have been made to divide patients into three risk groups based on the combination of risk factors present after radical hysterectomy. In Europe/USA and Japan, however, a fundamental difference exists in the indications for radical surgery, highlighting differences in the concept of PORT; “adjuvant pelvic irradiation after stage IB-IIA patients after complete resection” in Europe/USA and “pelvic irradiation after surgery irrespective of initial clinical stage and surgical margin status” in Japan. Thus, it is questionable whether scientific evidence established in Europe/USA is applicable to Japanese clinical practice. The purpose of this article is to review the role of PORT by interpreting the results of clinical studies. The contents of the current article were presented as an educational lecture on the 64^th JRS meeting (April 2005) in Yokohama.