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Biomedical subjects

A H Russell

Publications and source records attributed to A H Russell.

At least 19 recordsLinked to original sources
PubMed2000

Anal sphincter conservation for patients with adenocarcinoma of the distal rectum: long-term results of radiation therapy oncology group protocol 89-02.

PURPOSE: To assess the outcome of a multi-institutional, national cooperative group study attempting functional preservation of the anorectum for patients with limited, distal rectal cancer. METHODS AND MATERIALS: Between September 21, 1989 and November 1, 1992, a Phase II trial of sphincter-sparing therapy was conducted for patients with clinically mobile rectal cancers located below the pelvic peritoneal reflection. Protocol treatment was designed for patients who were, in the judgement of their attending surgeon, unsuitable for anal sphincter conservation in the context of anterior resection, and would have required abdominoperineal resection (APR) as conventional surgical therapy. Primary cancers were estimated to be 4 cm or less in largest clinical diameter, and occupied 40% or less of the rectal circumference. Chest radiography and computerized axial tomography (CT) of the abdomen and pelvis excluded patients with overt lymphatic or hematogenous metastases. Protocol surgery was intended to remove the primary cancer by en-bloc, transmural excision of an ellipse of rectal wall by transanal, transcoccygeal, or trans-sacral technique, while conserving the anal sphincter. Based on tumor size, T classification, grade, and adequacy of surgical margins, patients were allocated to one of three treatment assignments: observation, or adjuvant treatment with 5-fluorouracil (5-FU) and one of two different dose levels of local-regional radiation. After completion of protocol therapy, patients were observed with follow-up that included periodic general physical and rectal examination, determinations of CEA, abdominopelvic CT, chest radiography, and surveillance endoscopy. Sixty-five eligible and analyzable patients were registered. RESULTS: With minimum follow-up of 5 years and median follow-up of 6.1 years, 11 patients have failed: 3 patients recurred local-regionally only, 3 patients had distant failure alone, and 5 patients manifested local-regional and distant failure. Eight patients died of intercurrent illness. Local-regional failure correlated with T-category revealed: T1 1/27 (4%), T2 4/25 (16%), and T3 3/13 (23%). Local-regional failure escalated with percentage involvement of the rectal circumference: 2/31 (6%) among patients with cancers involving 20% or less of the rectal circumference, and 6/34 (18%) among patients with cancers involving 21-40% of the circumference. Distant dissemination rose with T-category with 1/27 (4%) T1, 3/25 (12%) T2, and 4/13 (31%) T3 patients manifesting hematogenous spread. Eight patients (12%) required temporary or permanent colostomy. Five of 8 patients with local-regional recurrence achieved local-regional control with management including surgery, although 4 of these patients subsequently developed distant dissemination. Three patients (5%) had persistent, uncontrolled, local disease. Actuarial freedom from pelvic relapse at 5 years is 88% based on the entire study population, and 86% for the less favorable patients treated with adjuvant radiation and 5-FU. CONCLUSION: Conservative, sphincter-sparing therapy is a feasible alternative treatment for selected patients with limited cancer involving the middle and lower rectum. Risk of both local and distant failure appears to escalate with increasing T-category (depth of invasion). Results achieved in the multi-institutional, cooperative group setting approximate results reported from single institutions.

Adult↗
PubMed1999

Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group.

CONTEXT: Carcinoma of the esophagus traditionally has been treated by surgery or radiation therapy (RT), but 5-year overall survival rates have been only 5% to 10%. We previously reported results of a study conducted from January 1986 to April 1990 of combined chemotherapy and RT vs RT alone when an interim analysis revealed significant benefit for combined therapy. OBJECTIVE: To report the long-term outcomes of a previously reported trial designed to determine if adding chemotherapy during RT improves the survival rate of patients with esophageal carcinoma. DESIGN: Randomized controlled trial conducted 1985 to 1990 with follow-up of at least 5 years, followed by a prospective cohort study conducted between May 1990 and April 1991. SETTING: Multi-institution participation, ranging from tertiary academic referral centers to general community practices. PATIENTS: Patients had squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, adequate renal and bone marrow reserve, and a Karnofsky score of at least 50. Interventions Combined modality therapy (n = 134): 50 Gy in 25 fractions over 5 weeks, plus cisplatin intravenously on the first day of weeks 1, 5, 8, and 11, and fluorouracil, 1 g/m2 per day by continuous infusion on the first 4 days of weeks 1, 5, 8, and 11. In the randomized study, combined therapy was compared with RT only (n = 62): 64 Gy in 32 fractions over 6.4 weeks. MAIN OUTCOME MEASURES: Overall survival, patterns of failure, and toxic effects. RESULTS: Combined therapy significantly increased overall survival compared with RT alone. In the randomized part of the trial, at 5 years of follow-up the overall survival for combined therapy was 26% (95% confidence interval [CI], 15%-37%) compared with 0% following RT. In the succeeding nonrandomized part, combined therapy produced a 5-year overall survival of 14% (95% CI, 6%-23%). Persistence of disease (despite therapy) was the most common mode of treatment failure; however, it was less common in the groups receiving combined therapy (34/130 [26%]) than in the group treated with RT only (23/62 [37%]). Severe acute toxic effects also were greater in the combined therapy groups. There were no significant differences in severe late toxic effects between the groups. However, chemotherapy could be administered as planned in only 89 (68%) of 130 patients (10% had life-threatening toxic effects with combined therapy vs 2% in the RT only group). CONCLUSION: Combined therapy increases the survival of patients who have squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, compared with RT alone.

Adenocarcinoma↗
PubMed1999

Overexpression of p53 protein and outcome of patients treated with chemoradiation for carcinoma of the anal canal: a report of randomized trial RTOG 87-04. Radiation Therapy Oncology Group.

BACKGROUND: Despite encouraging results with chemoradiation as the primary means of managing carcinoma of the anal canal, approximately 20% of patients will develop a local recurrence. This study examined the prognostic significance of p53 nuclear protein overexpression in the pretreatment biopsies of patients treated with chemoradiation for epidermoid carcinoma of the anal canal. METHODS: All patients were treated in a prospective, randomized Radiation Therapy Oncology Group trial (RTOG 87-04) in which radiotherapy to the pelvis was compared with concurrent 5-fluorouracil (5-FU) or 5-FU and mitomycin-C. Formalin fixed, paraffin embedded blocks or unstained slides from the pretreatment biopsies of 64 patients were obtained from referring institutions and evaluated immunohistochemically with the polyclonal p53 antibody CM-1. A multivariate analysis was conducted to analyze overexpression of p53 in terms of locoregional control, no evidence of disease (NED), and overall survival. RESULTS: p53 protein was overexpressed in 48.4% of the cases. Although not statistically significant, there was a trend for patients whose tumors overexpressed p53 to have inferior locoregional control (52% vs. 72%, P = 0.13), NED survival (52% vs. 68%, P = 0.27), and absolute survival (58% vs. 78%, P = 0.14). Of all the pretreatment factors analyzed, only International Union Against Cancer stage was predictive of outcome in multivariate analysis. Among those patients whose tumors overexpressed p53, there was a trend toward improved outcome in the arm that received 5-FU and mitomycin-C compared with the arm that received 5-FU only. CONCLUSIONS: Overexpression of the p53 protein may be associated with inferior outcome for patients managed with definitive chemoradiation for epidermoid carcinoma of the anal canal.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Addition of chemotherapy to radiation therapy alters failure patterns by cell type within non-small cell carcinoma of lung (NSCCL): analysis of radiation therapy oncology group (RTOG) trials.

PURPOSE: To evaluate the influence of cell type within non-small cell carcinoma of lung (NSCCL) on failure patterns when chemotherapy (CT) is combined with radiation therapy (RT). METHODS AND MATERIALS: Data from 4 RTOG studies including 1415 patients treated with RT alone, and 5 RTOG studies including 350 patients also treated with chemotherapy (RT + CT) were analyzed. Patterns of progression were evaluated for squamous cell carcinoma (SQ) (n = 946), adenocarcinoma (AD) (n = 532) and large cell carcinoma (LC) (n = 287). RESULTS: When treated with RT alone, SQ was more likely to progress at the primary site than LC (26% vs. 20%, p = 0.05). AD and LC were more likely to progress in the brain than SQ (20% and 18% vs. 11%, p = 0.0001 and 0.011, respectively). No differences were found in intrathoracic and distant metastasis by cell type. When treated with RT + CT, AD was less likely to progress at the primary than either SQ or LC (23% vs. 34% and 40%, respectively; p = 0.057 and 0.035). AD was more likely than SQ to metastasize to the brain (16% vs. 8%, p = 0.03), and other distant sites (26% vs. 14%,p = 0.019). No differences were found in intrathoracic metastasis. LC progressed at the primary site more often with RT + CT than with RT alone (40% vs. 20%, p = 0.036). Death with no clinical progression was more likely with SQ than AD or LC for RT alone and RT + CT (p < 0.01). Brain metastasis was altered little by the addition of CT, but other distant metastases were significantly decreased (p < 0.001) in all cell types by the addition of CT. CONCLUSION: CT, although effective in reducing distant metastasis in all types of NSCCL, has different effects on the primary tumor by cell type, and has no effect on brain metastasis or death with no progression. Different treatment strategies should be considered for the different cell types to advance progress with RT + CT in NSCCL.

Adenocarcinoma↗
PubMed1998

Failure patterns by prognostic group determined by recursive partitioning analysis (RPA) of 1547 patients on four radiation therapy oncology group (RTOG) studies in inoperable nonsmall-cell lung cancer (NSCLC).

PURPOSE: To identify groups of patients who might benefit from more aggressive systemic or local treatment, based on failure patterns when unresectable NSCLC was treated by radiation therapy (RT) alone. METHODS: From 4 RTOG trials, 1547 patients treated by RT alone were analyzed for patterns of first failure by RPA class defined by prognostic factors, including KPS, weight loss, nodal stage, pleural effusion, age and radiation therapy dose. All patients had NSCLC AJCC Stage II, IIIA, or IIIB, KPS > 50, with no previous RT or chemotherapy. Progressions in the primary (within irradiated fields), thorax (outside irradiated area, but within thorax), brain and distant metastasis other than brain were compared (2-sided) for each failure category by RPA. RESULTS: The RPA classes were 4 distinct subgroups that had significantly different median survivals of 12.6, 8.3, 6.3 and 3.3 months for Classes I, II, III and IV, respectively, (all groups, p = 0.0002). There were 583, 667, 249 and 48 patients in Classes I, II, III and IV, respectively. Primary failure was seen in 27%, 25%, 21% and 10% for Classes I, II, III, and IV, respectively (I vs. IV, p = 0.014; II vs. IV, p = 0.022). Distant metastasis, including brain metastasis, occurred at significantly higher rates among Classes I and II (58% and 54%) than in Classes III and IV (42% and 27%). A higher rate (58%) of death without an identifiable site of failure was found in Class IV than in Classes I, II and III (27%, 28% and 36%, respectively). CONCLUSIONS: The data suggest that physiologic compromise from the intrathoracic disease in Class IV patients is sufficient to cause death before specific sites of failure became evident. Clinical investigations using treatments directed at specific sites of failure could lead to improved outcome for Class I, II and, possibly, Class III patients. Inclusion of Class IV patients in clinical trials may obscure outcomes.

Aged↗
PubMed1998

Ten-year outcomes for pathologic node-positive patients treated in RTOG 75-06.

PURPOSE: This study was conducted to see what fraction of prostate cancer patients with biopsy-proven nodes are free of cancer 10 years after radiation treatment. METHODS AND MATERIALS: RTOG protocol #75-06 included 90 patients with biopsy-proven pelvic nodal involvement treated with radiation. They have been continuously follow-up since treatment. When feasible, current prostate-specific antigen (PSA) levels have been solicited from patients clinically cancer-free (no evidence of disease, NED) at 10 years, to confirm cure. RESULTS: The 10-year survival was 29%, the 10-year clinical NED survival 7%. PSA levels were obtained in 2 of 5 10-year clinical NED patients, they were both less than 0.8 ng/ml. The 2 proven cures were both clinical stage T-3, Gleason Score 6 and 8, and had 2 and 1 positive nodes, respectively. Multivariate analysis showed Gleason sum was significantly associated with clinical survival without disease. CONCLUSION: A small fraction of node-positive patients are cured at 10-year follow-up by radiation therapy (2 of 90 with PSA +3 of 90 by clinical endpoints). Innovative treatment programs should be directed at node-positive patients in an effort to improve the fraction cured.

Disease-Free Survival↗
PubMed1998

Trends in the use of radiation and chemotherapy in the initial management of patients with carcinoma of the uterine cervix.

PURPOSE: The Commission on Cancer of the American College of Surgeons conducts Patient Care Evaluation studies to describe practice patterns and trends in disease management. This report surveys changing strategies in the initial treatment of patients with invasive cancer of the uterine cervix. METHODS AND MATERIALS: Using a standard data collection form designed by a multidisciplinary committee of specialists, cancer registrars at 703 hospitals submitted anonymous data on 11,721 total cervical cancer patients diagnosed in 1984 and 1990. RESULTS: Between the two study years, the use of radiation as all, or a component, of the initial course of therapy declined from 70 to 60.3%, coincident with a 32.3% increase in the use of hysterectomy alone and a 33.7% reduction in the use of radiation alone. The percentage of all patients receiving combined hysterectomy and radiation (preoperative or postoperative) remained virtually unchanged--10.2% in 1984, and 9.3% in 1990. However, women who were treated by hysterectomy in 1990 were less likely to receive radiation as part of their treatment than patients treated by hysterectomy in 1984. Among patients treated by radiation without hysterectomy, the use of intracavitary brachytherapy techniques substantially exceeded interstitial brachytherapy techniques in both study years. Among patients treated by local radiation without hysterectomy, the frequency of adjunctive chemotherapy use increased from 6.9% in 1984 to 24.8% in 1990, with chemotherapy and radiation increasingly administered concurrently rather than sequentially. Although differences based on age, histology, race/ethnicity, and insurance status were observed, these general management trends were seen in all groups. CONCLUSIONS: Changes in the utilization of radiation and surgery may reflect the increasing surgical involvement of gynecologic oncologists in the management of early stage cervical cancer, rather than significant alterations in the demographics of the disease. Although brachytherapy is recognized as an important component of radiation treatment, some patients may not receive the potential benefit of this modality. Despite controversy concerning its efficacy, the use of adjuvant systemic chemotherapy to supplement local treatment modalities appears to be increasing rapidly.

Adult↗
PubMed1997

Androgen suppression plus radiation versus radiation alone for patients with D1 (pN+) adenocarcinoma of the prostate (results based on a national prospective randomized trial, RTOG 85-31). Radiation Therapy Oncology Group.

PURPOSE: To evaluate the effect of immediate androgen suppression in conjunction with standard external beam irradiation vs. radiation alone on a group of pathologically staged lymph node-positive patients with adenocarcinoma of the prostate. METHODS AND MATERIALS: A national prospective randomized trial (RTOG 85-31) of standard external beam irradiation plus immediate androgen suppression vs. external beam irradiation alone was initiated in 1985 for patients with locally advanced adenocarcinoma of the prostate. One hundred seventy-three of the patients in this trial had biopsy-proven pathologically involved lymph nodes. Ninety-eight of these patients received radiation plus the immediate androgen suppression (LHRH agonist), while 75 received radiation alone with hormonal manipulation instituted at the time of relapse. RESULTS: With a median followup of 4.9 years, estimated progression-free survival with PSA < 1.5 ng/ml at 5 years was 55% for the patients who received radiation plus immediate LHRH agonist vs. 11% of the patients who received radiation alone with hormonal manipulation at relapse (p = 0.0001). Because all of these patients had locally advanced disease (i.e., pathologically positive lymph nodes), stage does not explain this difference in outcome, and Gleason grade was not statistically different between the two groups. Estimated absolute survival at 5 years for the radiation and LHRH group was 73 vs. 65% for the radiation alone group who received androgen suppression at relapse. Estimated disease-specific survival at 5 years was 82% for the radiation and immediate LHRH agonist group and 77% for the radiation-alone group. CONCLUSION: Patients with adenocarcinoma of the prostate and pathologically involved pelvic lymph nodes (pN+ or clinical stage D1) should be seriously considered for external beam irradiation plus immediate hormonal manipulation over radiation alone with hormonal manipulation at the time of relapse.

Adenocarcinoma↗
PubMed1997

Prophylactic chemoradiation of inguinofemoral lymph nodes in patients with locally extensive vulvar cancer.

OBJECTIVE: Primary surgical resection of locally advanced squamous cancer of the vulva may compromise the integrity of important midline structures such as the anus, clitoris, urethra, and vagina. Chemoradiation (synchronous radiation and cytotoxic chemotherapy) has been used as alternative initial treatment which may serve as definitive management for some patients, or may reduce the scope and functional sequelae of subsequent surgery in others. Inguinofemoral node dissection is associated with substantial risk of both acute and late morbidity, prompting consideration of elective inclusion of groin nodes within the irradiated volume and deletion of subsequent groin surgery. Concern that disease relapse in the groins is potentially fatal suggested the prudence of formal outcome assessment of our recent experience with prophylactic treatment of clinically uninvolved groin nodes in the context of concurrent chemoradiation for locally advanced primary vulvar cancer. METHODS: A review was conducted of 23 previously untreated patients with locally advanced squamous cancer of the vulva (2 T2, 20 T3, 1 T4) and clinically uninvolved groin nodes (1969 FIGO stages 14 N0, 4 N1, and 5 N2 with negative node biopsies) who were treated since 1987 with chemoradiation administered to a volume electively including bilateral inguinofemoral nodes. These patients did not undergo subsequent groin surgery. RESULTS: With follow-up from 6 to 98 months (mean, 45.3 months; median, 42 months), no patient has failed in the prophylactically irradiated inguinofemoral nodes. No patient has developed lymphedema, vascular insufficiency, or neurological injury in a lower extremity, and no patient has experienced aseptic necrosis of a femur. CONCLUSIONS: Elective irradiation of the groin nodes in the context of initial chemoradiation for locally advanced vulvar cancer is an effective therapy associated with acceptable acute toxicity and minimal late sequelae. It constitutes a sensible alternative to groin dissection in this patient population.

Adolescent↗
PubMed1996

Diagnostic assessments in patients with invasive cancer of the cervix: a national patterns of care study of the American College of Surgeons.

Using a standard collection form designed by a multidisciplinary committee of specialists, cancer registrars at 703 hospitals submitted anonymous data on 11,721 patients with cervical cancer diagnosed during 2 study years, 1984 and 1990. Information concerning the initial use of diagnostic assessments was analyzed with respect to the potential influences of clinical stage, patient age, race/ethnicity, insurance status, and modalities of therapy employed. Estimates of the yield of diagnostic information for each test were correlated with clinical stage and patient age. Judged by the number of procedures performed, the intensity of pretreatment assessment declined between 1984 and 1990. Substantially increased use of the newer body imaging modalities (computerized axial tomography and magnetic resonance imaging) with high probabilities of revealing abnormalities attributed to cancer, balanced major declines in utilization of procedures historically important in staging and assessment (cystoscopy, proctoscopy, barium enema, excretory urography (intravenous pyelogram), bone scintography, and lymphangiography). Race/ethnicity and insurance status had no discernible independent impact on the intensity of diagnostic evaluation. Patients with more advanced clinical stages underwent more extensive testing, as did patients treated initially with radiation compared to surgery. Periodic review of assessment strategies would seem prudent to avoid widening discrepancies between sanctioned staging formalisms with endorsed and authorized appraisals and actual clinical practice.

Adult↗
PubMed1996

Integration of diagnostic imaging in the clinical management of cervical cancer.

Diagnostic imaging plays multiple roles during the initial assessment, treatment, and surveillance follow-up of patients with cervical cancer. Clarification of pretreatment disease extent aids in understanding prognosis, may influence selection of treatment modalities, and permits outcome comparison between different therapeutic interventions employed in similar groups of patients. Recently, use of historically important imaging assessments has declined precipitously, coincident with the increased use of contemporary imaging modalities not yet acknowledged by the International Federation of Gynecology and Obstetrics staging. In the United States, approximately 50% of the patients with invasive cancer will receive all, or a portion, of their initial treatment with radiation therapy. Clarification of the target volumes for radiotherapy, including both teletherapy and brachytherapy components, enables delivery of radiation therapy, with maximal confidence that all identifiable cancer is within the treatment field and normal tissues are excluded to the greatest extent possible. Imaging assessments can help select patients most likely to benefit from aggressive salvage therapies. Identification of sites of recurrence provides guidance for refinements in existing therapies and is an important element in the prospective evaluation of new treatments. As postmortem examination of patients who have died of cancer becomes a rare event, antemortem imaging can serve as an alternative to the traditional autopsy in determining cause of death and ultimate patterns of failure. Future challenges for diagnostic imaging include addressing the need for disciplined, prospective evaluation of emerging imaging technologies and, when sensible, rational integration of widely available, standardized imaging modalities into algorithms for initial staging and subsequent monitoring of patients treated for invasive cervical cancer.

Diagnostic Imaging↗
PubMed1996

Radiation palliation of cervical cancer.

Radiation is a useful modality for palliation of local-regional disease in patients with cervical cancer who require palliation because of distant metastases, extensive local-regional disease, medical consideration, or patient concerns. Two radiation schedules have been reported on for the treatment of advanced pelvic disease including cervical cancer. The large single-dose schedule consisted of 10-Gy fractions repeated at monthly intervals to a maximum of 30 Gy. This schedule has produced good palliative results with symptomatic improvement in approximately 50% of patients and objective response in 35%-80%. However, severe late toxicity was shown to be as high as 42% (actuarial). The second schedule tested by the Radiation Therapy Oncology Group consisted of 3.7-Gy fractions given twice a day for 2 days (14.8 Gy) repeated after 2-4 weeks for a maximum of 44.4 Gy. There were 284 patients accrued, and the subgroup of 61 cervical cancer patients is analyzed in this article. The subjective response (50%-100% complete response) and objective response (53%) were similar to those observed with the large single-fraction schedule. The late toxicity was significantly lower (7%-actuarial). For patients who may survive 6 months or longer, this second schedule is preferable.

Female↗
PubMed1995

Is there really a difference in survival of women with squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma of the cervix?

BACKGROUND: The authors' aim was to assess whether there is a difference in biologic behavior and survival in comparing adenocarcinoma (AdCA), squamous cell carcinoma (SCC), and adenosquamous carcinoma (Ad/SC) of the cervix. METHODS: Cancer registrars at 703 hospitals submitted anonymous data on 11,157 patients with cervical cancer diagnosed and/or treated in 1984 and 1990 for a Patient Care Evaluation Study of the American College of Surgeons. Among these patients, 9351 (83.8%) had SCC; 1405 (12.6%), AdCA; and 401 (3.6%), Ad/SC cancers. There were no significant changes in percentages of the different histologic types between the study years 1984 and 1990, nor was the patient distribution different regarding age, race/ethnicity, and socioeconomic background for each histologic group. Furthermore, the distribution of patients who had had a hysterectomy did not change between 1984 and 1990. RESULTS: A larger percent of patients with SCC (63.8%) than those with Ad/SC (59.8%) or AdCA (50.2%) had tumors larger than 3 cm at greatest dimension. Early stage patients (IA, IB, IIA) often were treated by hysterectomy alone (45.5%) or combined with radiation (21.1%). The remaining patients (21.9%) received radiation alone. Of the patients with clinical stage I disease, 7.6% of Ad/CA patients, 15.5% of Ad/SC patients and 12.6% of SCC patients had positive nodes. Although patients with SCC had higher survival rates for all four clinical stages (I-IV), the differences were only significant for Stage II patients. Patients with clinical stage IB SCC and AdCA treated by surgery alone were found to have significantly better survival rates (93.1% and 94.6% at 5 years, respectively) than women treated by either radiation alone or a combination of surgery and radiation (P < 0.001, both histologic comparisons). For women with Ad/SC tumors, however, the 5-year survival rate was 87.3% for those receiving combined treatment compared with those receiving surgery alone (69.2%) or radiation alone (79.2%). However, these survival curves were not significantly different (P = 0.496). One hundred six patients with positive nodes were available for analysis. The 5-year survival rate of patients with SCC and positive nodes was 76.1%. Surprisingly, patients with Ad/SC and positive nodes had the highest 5-year survival rate (85.7%), whereas, women with AdCA and positive nodes had a sharply reduced 5-year survival rate (33.3%). The curves were significantly different (P < 0.01). For patients with clinical stage I, the risk factors for age, tumor size, nodal status, histologic features, and treatment were analyzed with Cox's multivariate regression. In this analysis, subset IB, greater tumor size, age 80 or older, and positive nodal status were each independently significant for poorer survival. Patients who were treated by surgery alone had a significantly better survival than patients who had other types of treatment or no treatment. Histologic characteristics had no significant effect on survival. In the analysis of patients with pathologic stage I disease, those with SCC had significantly poorer survival and those with Ad/SC had significantly better survival than patients with Ad/CA. Positive nodes had no significant independent effect on survival. In another analysis, tissue type was not found to be an important factor in recurrence time. CONCLUSIONS: 1. Ad/CA and Ad/SC tumors were found to represent 12.6% and 3.6%, respectively, of a large series (N = 11,157) of cervical cancers diagnosed in 1984 and 1990 and reported to the Commission on Cancer of the American College of Surgeons. 2. Two thirds of women with early clinical stage disease (IA, IB, IIA) had hysterectomy as all or part of their primary therapy. 3. No significant differences were found in 5-year survival among the three tissue types in any clinical stage except American Joint Committee on Cancer stage II.

Adenocarcinoma↗
PubMed1993

Interruptions of high-dose radiation therapy decrease long-term survival of favorable patients with unresectable non-small cell carcinoma of the lung: analysis of 1244 cases from 3 Radiation Therapy Oncology Group (RTOG) trials.

PURPOSE: To determine if prolonged treatment time adversely affects survival for patients with inoperable non-small cell carcinoma of the lung. METHODS AND MATERIALS: Patients enrolled on three randomized studies (RTOG 8311, 8321, 8403) between 1983-1989 formed the database. Previous analyses found that the addition of thymosin (8321) or prophylactic cranial irradiation (8403) failed to prolong survival: both studies used thoracic irradiation with standard fractionation to 55-60 Gy in 30 fractions. In 8311, patients were treated by hyperfractionated radiation therapy to randomly assigned total doses of 60.0 Gy, 64.8 Gy, 69.6 Gy, 74.4 Gy or 79.2 Gy, 1.2 Gy twice daily, 5 days per week. Patients analyzed received +/- 4% of the assigned total dose and lived > 90 days (to ensure that all patients would have completed treatment). Completion < 5 days beyond protocol specifications was classified as "per protocol." Elapsed treatment time exceeding specifications by 5-9 days was a minor deviation, 10-13 days was a major deviation-acceptable, and > or = 14 days was a major deviation-unacceptable. Absolute survival was the endpoint to evaluate the effect of delays. The log rank statistic was used to test for survival differences in the univariate setting, the Cox regression model was used in the multivariate setting. RESULTS: Of 293 patients treated with standard fractionation, eight (2.7%) had deviations from the specified treatment time (six minor, two major-acceptable). With hyperfractionation, 90 (15%) patients had deviations (40 minor, 21 major-acceptable, 29 major-unacceptable). As the assigned dose increased, the deviation rate increased (9.7% for 60.0 Gy vs. 20.8% for 79.2 Gy). Survivals for hyperfractionation patients with any deviations in treatment time were significantly shorter than those treated "per protocol" (p = 0.16): estimated 2- and 5-years rates were 24% and 10% versus 13% and 3%, respectively. Multivariate analyses showed the delay effect to be entirely in patients treated with 69.6 Gy or higher; there was also dependence upon the patients' prognosis. In patients with favorable prognosis (KPS 90-100, weight loss < or = 5%, no N3), the difference in survival was pronounced (33% and 15% vs. 14% and 0% at 2- and 5-years, respectively). Such differences were not found in patients with unfavorable prognostic factors. CONCLUSIONS: Interruptions delaying completion of planned radiation therapy were more frequent with higher total doses (> or = 69.6 Gy). Favorable patients (high KPS, little weight loss, < N3 nodal metastasis) had markedly adverse effects on long-term survival associated with delays to completion of the planned total dose.

Adult↗
PubMed1993

Accelerated hyperfractionated hepatic irradiation in the management of patients with liver metastases: results of the RTOG dose escalating protocol.

PURPOSE: This study was prepared to address two objectives: (a) to determine whether progressively higher total doses of hepatic irradiation can prolong survival in a selected population of patients with liver metastases; (b) to refine existing concepts of liver tolerance for fractionated external radiation employing a fraction size which might be appropriate in clinical protocols evaluating elective or adjuvant radiation of the liver. METHODS AND MATERIALS: One hundred seventy-three analyzable patients with computed tomography measurable liver metastases from primary cancers of the gastrointestinal tract were entered on a dose escalating protocol of twice daily hepatic irradiation employing fractions of 1.5 Gy separated by 4 hr or longer. Sequential groups of patients received 27 Gy, 30 Gy, and 33 Gy to the entire liver and were monitored for acute and late toxicities, survival, and cause of death. Dose escalation was implemented following survival of 10 patients at each dose level for a period of 6 months or longer without clinical or biochemical evidence of radiation hepatitis. RESULTS: The use of progressively larger total doses of radiation did not prolong median survival or decrease the frequency with which liver metastases were the cause of death. None of 122 patients entered at the 27 Gy and 30 Gy dose levels revealed clinical or biochemical evidence of radiation induced liver injury. Five of 51 patients entered at the 33 Gy level revealed clinical or biochemical evidence of late liver injury with an actuarial risk of severe (Grade 3) radiation hepatitis of 10.0% (+/- 7.3% S.E.) at 6 months, resulting in closure of the study to patient entry. CONCLUSION: The study design could not credibly establish a safe dose for hepatic irradiation, however, it did succeed in determining that 33 Gy in fractions of 1.5 Gy is unsafe, carrying a substantial risk of delayed radiation injury. The absence of apparent late liver injury at the 27 Gy and 30 Gy dose levels suggests that a prior clinical trial of adjuvant hepatic irradiation in patients with resected colon cancer may have employed an insufficient radiation dose (21 Gy) to fully test the question.

Clinical Protocols↗