Postoperative adjuvant therapy of rectal cancer: an analysis of disease control, survival, and prognostic factors

Between 1976 and 1984, 139 patients with rectal cancer were treated with complete surgical resection and postoperative adjuvant pelvic radiation therapy with or without chemotherapy. In this group, tumor extended beyond the bowel wall or involved lymph nodes or both. Irradiation was begun between 15 and 182 days postoperatively (median delay, 42 days). The radiation was delivered with 4-, 6-, or 10-MV photons given 5 days per week at 1.8 to 2.0 Gy per fraction. Total doses ranged from 3.8 to 64.4 Gy (median, 50 Gy). The fields were AP:PA in 49 and AP:PA plus laterals in 90. Forty-four received concurrent chemotherapy: 5-fluorouracil and semustine in 37, and 5-fluorouracil alone in seven. Follow-up in survivors ranged from 2 to 10 years (median, 4.2 years). This analysis includes all failures, both initial and subsequent sites of failure. Local failure occurred in 30 (22%) of the 139 patients overall, 6 (18%) of 33 in Stage B-2, 1 of 3 in Stage B-3, 2 (10%) of 20 in Stage C-1, 20 (26%) of 76 in Stage C-2, and 1 (14%) of 7 in Stage C-3. Five-year actuarial survival was 59% overall, 82% in Stage B-2, 79% in Stages B-2 and B-3, 89% in Stage C-1, 41% in Stage C-2, and 42% in Stages C-2 C-3. The following prognostic factors were independently associated with poorer survival and increasing distant failure: lymph node involvement, tumor extension beyond the bowel wall, and high histologic grade. Use of chemotherapy was associated with a significant improvement in survival and decrease in distant failure. No single factor was significantly associated with local failure. Adequate perineal coverage after combined abdominoperineal resection yielded significantly fewer perineal failures. Overall, serious complications developed in 7%, but none was fatal. Treatment recommendations and optimal treatment techniques are discussed.     

Tumor control in definitive irradiation of localized carcinoma of the prostate

At the Mallinckrodt Institute of Radiology, Washington University, 343 patients with carcinoma of the prostate were treated with definitive radiotherapy. All patients are available for minimal 3 year follow-up; the median period of observation is 5.2 years. The incidence of pelvic recurrence with or without distant metastases was 0% in 10 patients with Stage A2, 11% in 113 patients with Stage B, 34% in 204 patients with Stage C, and 40% in 16 patients with Stage D1. There was no significant difference in pelvic tumor control when correlated with the degree of differentiation of the tumors in each stage. In Stage B, patients who exhibited complete regression 3 months after completion of therapy had a pelvic failure rate of 5%, those with 50-75% regression-8% and less than 50% regression-18%. In Stage C, patients with more than 50% tumor regression had a pelvic failure rate of 25%, in contrast to 37% when less than 50% regression was noted at 3 months after completion of irradiation. However, there was no correlation between tumor regression and NED survival. In patients with Stage B, there was no significant correlation between doses of irradiation ranging from 6000 to 7000 cGy and pelvic tumor control. In Stage C, patients receiving doses higher than 6500 cGy had a probability of failure rate in the pelvis of 25% (40/173), in comparison with 44% with doses between 6000-6500 cGy (15/32). The 10 year NED survival for Stage A2 was 100%, Stage B-70%, and Stage C-40%. In Stage B, there was no correlation between local tumor control and 5 year overall survival. However, at 10 years 88 patients without evidence of local failure or distant metastases had a survival rate of 70% in contrast to only 25% if they recurred. In Stage C, 110 patients without local recurrence or distant metastases had a 40% 10 year survival in contrast to 20% in 55 patients who had pelvic recurrence (with or without distant metastases) and 39 patients with distant metastases only. In 105 patients with Stage B tumor controlled in the pelvis, the incidence of distant metastases was 16%, in contrast to 50% in eight patients with pelvic failure. In Stage C, only 26% of 149 patients with pelvic tumor controlled developed distant disease, versus 60% in 55 patients failing in the pelvis. Ninety-five percent of the pelvic failures and 80% of the distant metastases appeared within 5 years after therapy. The administration of hormones did not significantly influence either the probability of pelvic tumor control or the appearance of distant metastases.     

The effect of dose on local control of prostate cancer

Three patterns of care outcome surveys in prostate cancer totalling 1516 patients had been combined and analyzed for the effect of dose on infield recurrence. There are significant dose effects observed in the overall data (1516 patients, p = .003), Stage B cancers (725 patients, p = .004) and Stage C cancers (624 patients, p = .059). No dose effect was observed for Stage A cancers (168 patients, p = .217) within the dose range observed (5500 cGy to greater than 7000 cGy). For patients with Stage B cancer one may conclude that dose between 6000 cGy and 6999 cGy is appropriate. Patients treated to less than 6000 cGy show a highly significant increase in local failure. Patients treated to greater than 7000 cGy do not show a demonstrable improvement in local control, but do show an increase in complications. Patients with Stage C cancer appear to require dose that is equal or greater than 7000 cGy to obtain the best local control, and the potential increased morbidity of these high doses appears to be justified in this stage of the disease. Patients who have been given hormonal therapy more than 1 month prior to radiation therapy show an increase in local failure rate for all stages of cancer. This is presumed to be the selection of poor risk patients for adjuvant hormonal treatment or by referring non-responding hormone treated patients for radiation therapy. Histologic grade exerts a major influence on local failure for patients with Stage C disease (p = less than .001), identifying an important stratification point for prospective clinical trials and a sub-group for which it is important to develop strategies for improving local control. The policy of treating all stages of prostate cancer with the same dose is not supported by these data.     

Cervical carcinoma metastatic to para-aortic nodes: extended field radiation therapy with concomitant 5-fluorouracil and cisplatin chemotherapy: a gynecologic oncology group study

Purpose: A multicenter trial of chemoradiation therapy to evaluate the feasibility of extended field radiation therapy (ERT) with 5-fluorouracil (5-FU) and cisplatin, and to determine the progression-free interval (PFI), overall survival (OS), and recurrence sites in patients with biopsy-confirmed para-aortic node metastases (PAN) from cervical carcinoma.

Methods and Materials: Ninety-five patients with cervical carcinoma and PAN metastases were entered and 86 were evaluable: Stage I—14, Stage II—40, Stage III—27, Stage IVA—5. Seventy-nine percent of the patients were followed for 5 or more years or died. ERT doses were 4500 cGy (PAN), 3960 cGy to the pelvis (Stages IB/IIB), and 4860 cGy to the pelvis (Stages IIIB/IVA). Point A intracavitary (IC) doses were 4000 cGy (Stages IB/IIB), and 3000 cGy (Stages IIIB/IVA). Point B doses were raised to 6000 cGy (ERT + IC) with parametrial boost. Concomitant chemotherapy consisted of 5-FU 1000 mg/m²/day for 96 hours and cisplatin 50 mg/m² in weeks 1 and 5.

Results: Eighty-five of 86 patients completed radiation therapy and 90% of patients completed both courses of chemotherapy. Gynecologic Oncology Group (GOG) grade 3–4 acute toxicity were gastrointestinal (18.6%) and hematologic (15.1%). Late morbidity actuarial risk of 14% at 4 years primarily involved the rectum. Initial sites of recurrence were pelvis alone, 20.9%; distant metastases only, 31.4%; and pelvic plus distant metastases, 10.5%. The 3-year OS and PFI rate were 39% and 34%, respectively, for the entire group. OS was Stage I—50%, Stage II—39%, and Stage III/IVA—38%.

Conclusions: Extended field radiation therapy with 5-FU and cisplatin chemotherapy was feasible in a multicenter clinical trial. PFI of 33% at 3 years suggests that a proportion of patients achieve control of advanced pelvic disease and that not all patients with PAN metastases have systemic disease. This points to the importance of assessment and treatment of PAN metastases.     

Hyperfractionated radiation therapy and concurrent 5-fluorouracil, cisplatin and mitomycin-C in head and neck carcinoma. A pilot study.

Seventeen patients were entered into a Phase I/II trial of concurrent hyperfractionated radiation therapy (7,440 cGy total dose; 120 cGy b.i.d.) combined with constant infusion of 5-fluorouracil (5-FU) (1,000 mg/m2/24 hours for 72 hours) and cisplatin (DDP) (50 mg/m2) for a total of three cycles. Thirteen patients had Stage IV disease; three, Stage III disease; and one, Stage II hypopharyngeal disease. Thirteen of 17 patients had positive cervical lymph nodes, and the mean size of the largest lymph node was 5.5 x 5.1 cm. The patients were not treated with planned adjunctive surgery except for one patient who had a radical neck dissection for massive, rapidly growing cervical adenopathy, which recurred promptly within 1 month before the initiation of protocol therapy. After the initial six patients were entered, mitomycin-C (Mito 8 mg/m2) was added during the second cycle. All the patients completed the planned course of radiotherapy with a median dose of 7,440 cGy and a mean dose of 7,248 cGy except for two patients who died--one from toxicity and the other, suicide. The predominant toxicity was mucositis, which was grade 3/4 in 11 of 15 patients, resulting in an average interruption of radiation therapy of 12 days. Weight loss was significant and was on the average 12% of baseline weight. Hematological toxicity was mild in the 5-FU/DDP group (only one grade 3 toxicity of six) and severe in the 5-FU/DDP/Mito-treated patients (five of eight patients having grade 3/4 toxicity including one leukopenic pneumonitis death). Additional toxicity included one parapharyngeal cellulitis, which responded to antibiotics. Noncompliance with the complex regimen was only seen in three patients. One patient refused b.i.d. radiation therapy, and one patient refused further chemotherapy after the first cycle. Additionally, one patient who had a severe ethanol withdrawal reaction during the first cycle of 5-FU/DDP did not receive further chemotherapy. The complete response rate of both primary site and neck by the protocol regimen alone was 71%. However, two patients, one from each group, did undergo salvage neck dissection, and the locoregional control is currently 73%, with a mean follow-up time of 18.4 months. The feasibility of combining hyperfractionated radiation therapy with aggressive concurrent chemotherapy was demonstrated. The response and local control rate justifies the added toxicity of concurrent chemotherapy and radiation therapy.     

Final report of Intergroup Trial 0122 (ECOG PE-289, RTOG 90-12): Phase II trial of neoadjuvant chemotherapy plus concurrent chemotherapy and high-dose radiation for squamous cell carcinoma of the esophagus

PURPOSE: To determine the outcome of neoadjuvant chemotherapy followed by concurrent chemotherapy plus high-dose radiation therapy in patients with local/regional squamous cell carcinoma of the esophagus. METHODS AND MATERIALS: Forty-five patients with clinical Stage T1-4N0-1M0 squamous cell carcinoma were entered on a prospective single-arm study, of which 38 were eligible. Patients received 3 monthly cycles of 5-FU (1000 mg/m2/24 h x 5 days) and cisplatin (100 mg/m2 day 1; neoadjuvant segment) followed by 2 additional monthly cycles of 5-FU (1000 mg/m2/24 h x 5 days) and cisplatin (75 mg/m2 day 1) plus concurrent 6480 cGy (combined modality segment). The median follow-up in surviving patients was 59 months. RESULTS: For the 38 eligible patients, the primary tumor response rate was 47% complete, 8% partial, and 3% stable disease. The first site of clinical failure was 39% local/regional and 24% distant. For the total patient group, there were 6 deaths during treatment, of which 9% (4/45) were treatment related. The median survival was 20 months. Actuarial survival at 3 years was 30%, and at 5 years, 20%. CONCLUSION: This intensive neoadjuvant approach does not appear to offer a benefit compared with conventional doses and techniques of combined modality therapy. However, high dose radiation (6480 cGy) appears to be tolerable, and is being tested further in Intergroup Trial INT 0123.     

Survival and analysis of failure following hydroxyurea, 5-fluorouracil and concomitant radiation therapy in poor prognosis head and neck cancer.

Thirty-nine patients with head and neck cancer were entered into Phase I-II study of simultaneous radiation therapy with continuous infusion fluorouracil at 800 mg/m2/day and escalating doses of hydroxyurea. Twenty of these patients had recurrent disease after previous surgery and/or radiation therapy (group 1). Nineteen patients had not received prior local therapy but had advanced-stage disease (group 2). Cycles were repeated every other week until the completion of radiation therapy. The median follow-up was 32 months. Patients with recurrent disease were generally treated with palliative doses of radiation (median dose 5,000 cGy) while previously untreated patients received radiation with curative intent (median dose 7,040 cGy). The response rate for 15 evaluable patients with recurrent disease was 93% with 40% of patients achieving a complete response. For 17 evaluable patients without recurrent disease the response rate was 100%, with a complete response rate of 71%. This regimen exhibited a high activity and significant palliative benefit in group 1 patients. However the local control rate was 25% (5/20) because the majority of patients in this group eventually developed a local recurrence. The local control rate for group 2 patients was 84% (16/19). The higher local failure rate in group 1 patients appeared to be attributable to the palliative doses of radiation delivered and the fewer cycles of treatment received. We conclude that this regimen has palliative benefit in patients who have failed prior local therapy and has the potential for cure in patients with poor prognosis advanced stage disease as well.     

Prostatic carcinoma: limited field irradiation

This is a retrospective study of 251 patients with histologically proven adenocarcinoma treated primarily with limited field radiotherapy techniques, under the principle direction of authors JMV and JPG, between 1968 and 1981 in San Francisco, California. All patients are followed for a minimum of 3 years; mean follow-up is 7.3 years. Routine clinical staging procedures included: H&P, digital prostate exam, cystoscopy, biopsy, blood studies including serum acid phosphatase, and imaging studies including chest X ray, IVP, bone survey or radionucleotide bone scan, and in recent years, pelvic CT scans. Twelve patients are Stage A1, 37-Stage A2, 50-Stage B, 140-Stage C1 and 12-Stage C2. Ninety percent of all cases and 85% of Stage C patients were treated with limited fields to the prostate and periprostatic volume only. Total doses were prescribed at midplane or isocenter and were generally 6500-7000 cGy, daily doses of 180-200 cGy, 5 days per week. Actuarial 5- and 10-year survival rates are: entire population-69% and 47%; Stage A1-74% and 50%; Stage A2-81% and 67%; Stage B-84% and 53%; Stage C1-63% and 42%; Stage C2-32% and 11%. The 5- and 10-year disease-free actuarial survivals are: entire population-71% and 50%; Stage A1-89% and 74%; Stage A2-82% and 69%; Stage B-71% and 52%; Stage C1-67% and 44%; Stage C2-0%. Sites of recurrence, alone or as a component of the failure pattern are: 37 (15%) local, 11 (4%) symptomatic regional recurrence (lower extremity edema, pelvic pain/sciatica, hydroureteronephrosis), and 87 (35%) distant metastasis. Seven (3%) had unknown sites of failure. Local-regional failure occurred in 42% of Stage C2 patients. Concomitant hormonal therapy has no survival impact on Stage C1 patients and poorly differentiated histology is associated with decreased determinate and disease-free survival rate of 5 years. Complications correlate with treatment technique, being more frequent with single field per day treatment plans. In patients treated with multiple fields per day or rotational plans, complications occur in less than 8% of patients and major complications have not occurred.     

Testicular seminoma. Results of the Yale University experience, 1964-1984

Eighty-three testicular seminoma patients were treated with radiation therapy from 1964 through 1984. Seventy-nine (95%) of the 83 patients had early disease that included 61 Stage I, 15 Stage IIA (pelvic or paraaortic lymph node involvement less than or equal to 5 cm), and 3 Stage IIB (pelvic or paraaortic lymph node involvement greater than 5 cm) patients. The 15-year actuarial survival for this group of Stage I and II patients was 95% (+/- 5%). Stage I patients were treated with a mean paraaortic/pelvic dose of 2924 cGy and only one patient developed recurrent disease. This recurrence was at the margin of the radiation field and probably represents a marginal miss. The Stage IIA patients were treated with slightly higher doses (mean, 3335 cGY) to the paraaortic/pelvic region and there were no recurrences. The three Stage IIB patients received tumor doses of 3245 cGy, 4090 cGy, and 4500 cGy, respectively, and there were no recurrences. Low dose prophylactic mediastinal and supraclavicular irradiation (mean, 2320 cGy) was used in 17 (94%) of the 18 Stage II patients and there were no mediastinal or supraclavicular recurrences. Four patients presented with advanced disease (one Stage III, three Stage IV) and the only disease-free survivor was treated with cisplatinum-based combination chemotherapy and radiation therapy. Three patients developed minor complications from the radiation therapy: one patient had persistent scrotal and leg edema and two patients treated with prophylactic mediastinal irradiation had chronic low leukocyte counts. Two of the 79 Stage I and II patients developed a second malignancy: one had bronchogenic carcinoma at the margin of a mediastinal field, and one had diffuse histiocytic lymphoma both in and out of the radiation therapy fields. The 15-year actuarial probability of developing a second malignancy was 3.3%. Radiation therapy after operation is a successful treatment option for most patients with Stage I and II seminoma.     

Dose-response and failure pattern for bulky or barrel-shaped stage IB cervical cancer treated by combined photon irradiation and extrafascial hysterectomy

From 1975 to 1987, 80 patients with bulky or barrel-shaped Stage IB cervical cancer were treated with preoperative irradiation and Cs-137 intracavitary implant therapy, before a planned extrafascial abdominal hysterectomy, using a consistent treatment policy. Of the hysterectomy specimens obtained, 37% were positive histologically at 89 +/- 2.3 days after the start of radiotherapy and at 4 to 6 weeks after the completion of radiation therapy. Sixty-three percent were negative after a total external and internal cervix irradiation dose of 9642 cGy at point T. The average point A dose contributed by intracavitary therapy was 2104 cGy. The survival rate at 5 years was 84%: At 10 years the survival rate was 78%. The failure pattern was analyzed for patients who had positive and negative specimens. The patients with positive specimens failed pelvically or pelvically and distantly. Patients with negative specimens failed in extrapelvic or distant metastatic sites. Preoperative radiotherapy led to excellent local and pelvic control of tumor, and the failures became predominantly distant metastases. The combined radiosurgical therapy was tolerated well and allowed surgical staging of disease. This permitted earlier and selective consideration of adjunctive therapy (i.e., paraaortic irradiation, chemotherapy, or chemoradiotherapy). The dose-response data give insight into the effects of photon radiotherapy on bulky or barrel Stage IB cervical cancers and correlate histologic status with failure pattern, outcome, and long-term survival.     

Clinical patterns of failure following stereotactic interstitial irradiation for malignant gliomas

The vast majority of patients treated for malignant gliomas with surgery, conventional radiation therapy, and systemic chemotherapy recur within 2 cm of their original disease site as documented by CT scanning. We have analyzed the clinical patterns of failure in patients treated with stereotactic interstitial irradiation (brachytherapy) for malignant gliomas in order to determine if this modality has altered the recurrence pattern in this disease. Between December 1985 and December 1989, 53 patients with malignant glioma were treated with stereotactic interstitial irradiation using temporary high activity iodine-125. Thirty-three patients were treated as part of a primary treatment protocol that included 5940 cGy external beam prior to implantation. Twenty patients were treated at time of recurrence. The median dose of radiation given at implantation was 5040 cGy for the primary lesions and 5450 cGy for the recurrent lesions. Twenty-two patients have suffered relapse as documented by clinical and radiographic studies. The predominant patterns of failure in these 22 patients were in the margins of the implant volume (8) and distant sites (10) within the CNS (distant ipsilateral or contralateral hemisphere, spinal axis) or extraneural. Thus, marginal and distant recurrences accounted for 82% of the relapses in our patients. We conclude stereotactic interstitial irradiation has changed the recurrence pattern in patients with malignant glioma with true local recurrence no longer being the predominant pattern of failure as is seen with conventional therapy.     

Radiotherapy alone for medically inoperable carcinoma of the cervix: stage IA and carcinoma in situ

The objective of this study was to define the role of radiotherapy alone for medically inoperable patients with Carcinoma in Situ (CIS) and Stage IA carcinoma of the uterine cervix. At the Mallinckrodt Institute of Radiology, Radiation Oncology Center from January 1959 through December 1986 21 patients with CIS and 34 with Stage IA were treated. All patients had histologically proven disease. The average age was 56 years for CIS and 51 years for Stage IA patients. Therapy for patients with CIS consisted of a single intracavitary insertion with a uterine tandem and colpostats. The average radiation doses were 4612 cGy to point A, 9541 cGy to the surface of the cervix, and 5123 milligram-hours (mgh). Radiotherapy for Stage IA tumors was delivered with intracavitary irradiation alone in 13 (average doses were 5571 cGy to point A, 10,430 cGy vaginal surface dose, and 6488 mgh). The other 21 patients were treated with external beam and intracavitary irradiation. The average whole pelvis dose was 1443 cGy with an additional 2354 cGy boost to the parametria with a midline stepwedge shield. The average intracavitary doses were 5200 cGy to point A, 10234 cGy to the vaginal surface, and 6293 mgh. None of the patients with CIS developed recurrent disease and none had severe sequelae of therapy. Only one patient with Stage IA developed recurrent disease in the pelvis. None developed metastatic disease. The severe complication rate was 5.9% (2/34) for Stage IA and only occurred in those receiving intracavitary irradiation and external beam irradiation. We conclude that irradiation consisting of intracavitary implants alone is excellent treatment for patients with medically inoperable Stage IA and CIS of the cervix.     

Primary radiation therapy for locally advanced breast cancer

The optimal local-regional treatment for patients with Stage III breast cancer has not been determined. To evaluate the effectiveness of radiation therapy as local treatment for such patients, the results of 192 patients (five with bilateral disease) treated with radiation therapy without mastectomy between July 1, 1968 and December 31, 1981 were reviewed. Excisional biopsy (gross tumor removal) was performed in only 54 of the 197 breasts. Patients typically received 4500 to 5000 cGy in 5 weeks to the breast and draining lymph nodes; a local boost to areas of gross disease was delivered to 157 patients. Multi-agent chemotherapy was given to 53 patients. The median follow-up was 65 months. The actuarial probability of survival for the entire group was 41% at 5 years and 23% at 10 years. The probability of relapse-free survival (RFS) was 30% at 5 years and 19% at 10 years. The addition of multi-agent chemotherapy was associated with a significantly improved 5-year RFS (40% versus 26%, P = 0.02). The 5-year survival rate was 51% for patients who received adjuvant multi-agent chemotherapy and 38% for patients who did not (P = 0.16). The actuarial rate of local-regional tumor control (not censored for distant failure) for all patients was 73% at 5 years and 68% at ten years, and the crude incidence of local-regional control was 78%. Local-regional tumor control was principally influenced by radiation dose. Patients who received 6000 cGy or greater to the primary site had a better 5-year rate of control in the breast than did patients who received less than 6000 cGy (83% versus 70%, P = 0.06). Significant complications were seen in 15 patients (8%); these included moderate or severe arm edema in six patients and brachial plexopathy in four patients. Cosmetic results at last evaluation were excellent or good in 56% of evaluable patients, fair in 25%, and poor in 19%. It is concluded that high-dose radiation therapy without mastectomy is an effective means of controlling local-regional tumor in patients with locally advanced breast cancer.     

Feasibility study of Californium-252 for the therapy of stage IV cervical cancer

Twenty patients with Stage IVA and IVB cervic cancers were treated with Californium-252 (Cf) neutron brachytherapy (NT) in a feasibility trial between 1976 and 1986. Eleven patients had Stage IVA disease; nine patients had Stage IVB disease. Patient compliance with therapy was poor in four of nine patients with Stage IVB disease, and the 50% survival time was 6 months. In Stage IVA disease there were 18% 3-year survivals. For those that failed, the 50% survival time was 7.5 months. Because of the frequency of disseminated metastases, effective adjuvant therapy needs to be developed to use after the tumor debulking therapy, especially for Stage IVB disease. A single early Cf-NT implant followed by 6000 cGy of whole-pelvis fractionated radiation would accomplish this adequately for local tumor control and palliation.     

Patterns and sites of failure in cervix cancer treated in the U.S.A. in 1978

Patterns of Care Study (PCS) conducted the second survey of carcinoma of the cervix in 1978. The data of this survey are derived from 565 patient questionnaires completed from 120 randomly selected facilities. Through these surveys PCS has set out to establish a profile of the practice of radiation therapy in the United States as well as determine the survival, local control rates, patterns of recurrence, complications, and relationship of these events with dose. This study deals with the patterns and sites of failure and relationship with dose to the paracentral and lateral points previously defined. The breakdown of patients according to the stage was as follows: Stage I = 203, Stage II = 243, Stage III = 115, undertermined = 4. Twenty-three percent of the patients failed within the field of irradiation, whereas 9% failed outside of the irradiated field. The infield failure rate increased as a function of stage from 9% in Stage I to 23% in Stage II and 48% in Stage III. Distant metastasis was the first site of failure in 4% of patients with Stage I, 7% for Stage II, 9% for Stage III, and 6% for the entire group. The cervix and vagina were the first site of recurrence in 20% of the patients. The cervical/vaginal recurrence rate increased as a function of stage from 7% in Stage I to 21% in Stage II, and 37% in Stage III. An analysis of the cervical/vaginal recurrences as a function of the average total dose to the paracentral points showed a decreased recurrence rate as a function of dose within the range of less than 6500 to 7999 cGy. The recurrence rate at 4 years decreased from 34% with a dose of less than 6500 cGy to 14% with a dose of 7500-7999 cGy. Above this dose level, this correlation of dose with recurrence was not observed. This correlation was also absent when the patients were studied according to the stage of the disease. The relationship of parametrial/sidewall failure and average dose to the lateral point was studied also, but no correlation was found except for patients with Stage III disease. The disease-free survival was studied for the entire group of patients and for the different stages as a function of average paracentral dose: less than 7500 cGy, 7500 to 8500 cGy, and greater than 8500 cGy. The disease-free survival was lower for the patients in the less than 7500 cGy group.(ABSTRACT TRUNCATED AT 400 WORDS)     

Preoperative radiation therapy in regionally localized stage III non-small cell lung carcinoma: long-term results and patterns of failure

Seventy-four patients from January 1975 through December 1982, with clinical Stage III Mo non-small cell carcinoma of the lung were treated at our Medical Center with a course of pre-operative radiation therapy to be followed by surgical resection. Radiation therapy consisted of delivering a total dose of 40 Gy with 200 cGy per fraction over a period of 4 weeks to the primary tumor in the lung and the regional lymph nodal areas. Surgical resection was attempted 4 weeks later. Fifty-eight percent of the patients had squamous cell carcinoma whereas the remaining had other histologies like adenocarcinoma, large cell carcinoma, or a combination thereof. All the patients except two were followed up to a minimum of 5 years or until death. Sixty-four patients (82%) had T3 tumors whereas mediastinal nodal involvement was found in 41 patients (55%). Fifteen patients (20%) did not have the operation because of tumor progression, patient's refusal or death. All but two surgically treated patients had tumor resection. Of these 19% had histologically negative specimens, 9 patients (16%) had microscopic disease only, and 37 patients had gross residual disease at the time of surgery. The actuarial 5-year survival and recurrence-free survival rates for the entire group were 20% and 24%, respectively. Patients with a pathologic response had an actuarial recurrence-free survival rate of 53% at 5 years whereas only 17% of those with gross residual disease at surgery had remained recurrence-free at 5 years. One-half of the patients with clinically uninvolved nodes were living recurrence-free at 5 years whereas only 20% of the patients with N2 disease did so. The patterns of failure according to the histology and stage of the disease will be presented.     

Phase I/II study of Fluosol-DA and 100% oxygen as an adjuvant to radiation in the treatment of advanced squamous cell tumors of the head and neck

Fluosol-DA 20% (Fluosol) is an emulsion of perfluorodecalin and perfluorotripropylamine, which has the ability to carry oxygen and has been shown to enhance the ability of radiation to control tumors in animal studies. Since November 1984, patients with unresectable squamous cell carcinomas of the head and neck have been enrolled in a study to evaluate the safety and potential efficacy of this adjuvant therapy. Forty-six patients were entered of which 37 completed radiation and are evaluable. Patients were infused weekly with Fluosol and then breathed 100% oxygen for a minimum of 30 minutes prior to and during radiation. Eleven patients received 5 infusions of 8 mL/Kg, four patients 6 infusions of 8 mL/Kg, five patients 5 infusions of 9 mL/Kg, seven patients 7 infusions of 7 mL/Kg and eight patients 8 infusions of 7 mL/Kg. Nine patients had Stage III disease, 20 patients Stage IV disease and 8 patients had failed previous therapy with chemotherapy and/or surgery. The radiation doses delivered ranged from 6600 cGy to 7500 cGy. The overall complete response rate for this group was 76%. All 9 Stage III patients were complete responders, 13 of 20 Stage IV responded and 6 of 8 with previous therapy were complete responders. The survival rate at 1 year was 67% for absolute and 78% as determinant. Of those patients achieving a complete response, 75% continued free of disease 1 year after therapy. Out of 254 total test doses, 11 patients experienced a reaction to the test dose of Fluosol. Of 235 total infusions 6 patients experienced a reaction during the Fluosol infusion with 7 patients experiencing post infusion reactions. These were readily controlled with diphenhydramine or acetominophen. Elevated liver enzymes were observed in some patients with a mean time to normalization of 102 days for alkaline phosphatase, 39 days for SGOT, and 46 days for SGPT.     

High-dose-rate remote afterloading intracavitary radiation therapy for cancer of the uterine cervix. A 20-year experience.

Retrospective analysis was performed on 1022 patients with squamous cell carcinoma of the uterine cervix who were treated with high-dose-rate remote afterloading intracavitary irradiation at the National Institute of Radiological Sciences, Angawa, Chiba-shi, Japan, from 1968 to 1982 in comparison with low-dose-rate intracavitary radiation therapy. The patient population consisted of 147 patients with Stage I disease, 256 patients with Stage II disease, 515 patients with Stage III disease, and 104 patients with Stage IV disease. Absolute 5-year survival rates for Stages Ib, IIa, IIb, IIIb, IVa, and IVb disease were 88.1%, 76.9%, 67.0%, 52.2%, 24.1%, and 13.3%, respectively. The rates of severe complication of Grades 3 and 4 were 4.1% for the rectosigmoid colon, 1.2% for the bladder, and 1.1% for the small intestine. In the case of Stage I to II disease, the optimal dose from intracavitary sources was suggested to be 2900 cGy +/- 200 cGy at point A, with 4 to 5 fractions of 600 to 700 cGy delivered over 4 to 5 weeks. These results suggested that high-dose-rate intracavitary radiation therapy provided clinical results comparable to those of a low-dose-rate technique.     

Radiation therapy for unresectable rectal cancer

The standard approach to patients with unresectable rectal cancer is pre-op radiation therapy followed by surgery. To determine the impact of RT on local failure and survival, we present an analysis of our preliminary results of this approach in patients with unresectable rectal cancer. A total of 22 patients were analyzed (9 primary, 13 recurrent). The median follow-up was 22 months. There were two groups of patients. Group 1 included 12 patients with unresectable tumors in whom surgery was planned following pre-operative radiation therapy. Group 2 included 10 patients in whom no surgery was planned following radiation therapy due to extensive pelvic bone destruction. The whole pelvis received 4680 cGy followed by a boost of 360-1440 cGy. Six underwent brachytherapy. For the total patient group, the 3-year actuarial survival was 52% (Group 1: 91% vs Group 2: 30%). Patterns of failure as a component of failure were: local failure (or local progression): 50%, abdominal: 23%, and distant: 9%. The dose of pelvic radiation had no significant impact on the local failure rate (5040 cGy: 55% vs greater than 5700 cGy:45%). None of the seven patients with negative margins developed local failure compared with 73% of those with positive margins. The complete resection rate in Group 1 patients was 58%, and all are alive without local failure. Further follow-up will be needed to determine the ultimate local failure and survival rates.     

Intraoperative electron beam radiation therapy for retroperitoneal soft tissue sarcoma

From December 1981 to December 1989, 20 patients with primary or recurrent retroperitoneal sarcoma received 4000 to 5000 cGy of external beam radiation therapy (EBRT) in conjunction with surgical resection and intraoperative radiation therapy (IORT). Seventeen of 20 patients underwent complete (14 patients) or partial (3 patients) resection. Three patients had shown evidence of metastases after EBRT by the time of surgery. The 4-year actuarial local control and disease-free survival rates of the 17 patients undergoing resection were 81% and 64%, respectively. Twelve patients received IORT at the time of resection for microscopic disease (10 patients) or gross residual sarcoma (2 patients). Of the ten patients receiving IORT for microscopic tumor, one patient has died of local failure and peritoneal sarcomatosis and two patients have died of distant metastases only. The remaining seven patients are disease-free. One patient treated for gross residual sarcoma has experienced a local failure 1 year after IORT and is without disease 7 years after salvage chemotherapy. The other patient treated for gross residual sarcoma has died of local failure. Five patients did not receive IORT at the time of resection because of the extensive size of the tumor bed. Three of these patients are disease-free with one patient alive with lung metastases and one patient dying of hepatic metastases. Aggressive radiation and surgical procedures appear to provide satisfactory resectability and local control with acceptable tolerance.