Biomedical subjects

B Emami

Publications and source records attributed to B Emami.

At least 19 recordsLinked to original sources

PubMed1999

Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC)

PURPOSE: To identify a clinically relevant and available parameter upon which to identify non-small cell lung cancer (NSCLC) patients at risk for pneumonitis when treated with three-dimensional (3D) radiation therapy. METHODS AND MATERIALS: Between January 1991 and October 1995, 99 patients were treated definitively for inoperable NSCLC. Patients were selected for good performance status (96%) and absence of weight loss (82%). All patients had full 3D treatment planning (including total lung dose-volume histograms [DVHs]) prior to treatment delivery. The total lung DVH parameters were compared with the incidence and grade of pneumonitis after treatment. RESULTS: Univariate analysis revealed the percent of the total lung volume exceeding 20 Gy (V20), the effective volume (Veff) and the total lung volume mean dose, and location of the tumor primary (upper versus lower lobes) to be statistically significant relative to the development of > or = Grade 2 pneumonitis. Multivariate analysis revealed the V20 to be the single independent predictor of pneumonitis. CONCLUSIONS: The V20 from the total lung DVH is a useful parameter easily obtained from most 3D treatment planning systems. The V20 may be useful in comparing competing treatment plans to evaluate the risk of pneumonitis for our individual patient treatment and may also be a useful parameter upon which to stratify patients or prospective dose escalation trials.

Adult↗

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

Response, toxicity, failure patterns, and survival in five Radiation Therapy Oncology Group (RTOG) trials of sequential and/or concurrent chemotherapy and radiotherapy for locally advanced non-small-cell carcinoma of the lung.

PURPOSE: The purpose of this study was to assess response, toxicity, failure patterns, and survival differences in three chemotherapy (ChT)/radiation therapy (RT) sequencing strategies for locally advanced non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Five completed Radiation Therapy Oncology Group (RTOG) trials for Stage II-IIIA/B inoperable NSCLC patients employed one of the three following strategy groupings: 1) sequential ChT followed by standard RT (60 Gy in 6 weeks); 2) combined sequential and concurrent ChT and standard RT (60 Gy in 6 weeks); or 3) concurrent ChT and hyperfractionated RT (69.6 Gy in 6 weeks). All five trials required KPS > or = 70; two trials (314 patients) required <5% weight loss and three trials (147 patients) had no minimum weight loss requirement. In all five trials the ChT used cisplatin with either vinblastine or oral etoposide. Combining data for the five trials yielded an evaluable group of 461 patients. The three methods of sequencing ChT and RT were evaluated for differences in response, acute and late toxicity, patterns of failure, and survival. Acute toxicity was defined as that occurring within 90 days from the start of RT. Late toxicity was defined as that occurring after 90 days from the start of RT. Acute or late toxicity > or = grade 3 was defined as severe. Site of first failure was recorded by date. In-field failure excluded distant metastasis as a failure and included only tissue in the RT treatment field. Overall progression-free survival (PFS) was defined as survival without evidence of intra- or extrathoracic tumor or death from any cause. RESULTS: Group 1 had a lower overall response rate (63%) compared to either Group 2 (77%) or Group 3 (79%), p = 0.03 and 0.003, respectively. Overall grade 4/5 acute toxicities were nearly equal between groups. The severe nonhematologic acute toxicities were significantly different by strategy group (p < 0.0001). Group 1 and 2 were not statistically different. Group 3 had significantly more patients with severe acute nonhematologic toxicity (55%) than either Group 1 (27%) or 2 (34%) with p < 0.0001 and p = 0.0005, respectively. This was due to a severe acute esophagitis rate of 34% for Group 3 versus 1.3% for Group 1 and 6% for Group 2 (p < 0.0001 for both comparisons). Overall grade 4/5 late toxicities did not differ by group. Severe late nonhematologic toxicities were different by group (p = 0.0098). Group 1 patients had significantly fewer severe late nonhematologic toxicities (14%) compared to patients in Groups 2 (26%) or 3 (28%) (p = 0.046 and 0.038, respectively). Severe late lung toxicity was 10% for Group 1 compared to 21% and 20% for Groups 2 and 3, respectively. Severe late lung toxicities differed by group (p = 0.033), but not severe late esophagitis (p = 0.077). There were no differences between the three strategy groups for patterns of first failure. The in-field failures were higher in Group 2 (71%) compared to Groups 1 (56%) and 3 (55%), p = 0.0478. Pairwise comparisons yielded p-values of 0.068 and 0.015 for Group 2 versus 1 and Group 2 versus 3, respectively. Three-year PFS was better in Group 2 (15%) and 3 (15%) compared to Group 1 (7%), but not statistically significant (p = 0.454). Similarly, in-field PFS was better in Group 2 (17%) and 3 (20%) than Group 1 (9%), but not significant (p = 0.167). There were improvements in 3-year survival for Group 2 (17%) and Group 3 (25%) compared to Group 1 (15%), but the differences were not statistically significant (p = 0.47). The same results were present for patients with less than 5% weight loss and patients with stage IIIA tumors. CONCLUSION: Thus, concurrent ChT and hyperfractionated RT had a higher incidence of severe acute esophageal toxicity. Severe late lung toxicity with concurrent ChT/hyperfractionated RT, as well as with induction ChT followed by concurrent ChT/standard RT, may be greater compared to sequential ChT/RT. (ABSTRACT TRUNCATED)

Antineoplastic Combined Chemotherapy Protocols↗

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

Results of treatment of patients with maxillary sinus carcinoma.

BACKGROUND: Information regarding results of treatment and possible prognostic factors in patients with maxillary sinus carcinoma is limited. METHODS: Between 1969-1995, 48 consecutive patients presented to the study department for curative treatment of maxillary sinus carcinoma. Tumor classification according to the American Joint Committee on Cancer staging system was T1 in 1 patient, T2 in 6 patients, T3 in 17 patients, and T4 in 24 patients. The N classification was NO in 43 patients, N2a in 1 patient, N2b in 3 patients, and N2c in 1 patient. Treatment to the primary site was comprised of surgery (Sx) and radiation therapy (RT) in 37 patients and RT alone in 11 patients. RESULTS: There was a difference in disease free survival between patients who underwent Sx + RT compared with patients who received RT alone; combined therapy results were more favorable. The most common pattern of recurrence was in the primary site, which was found in 22 of 48 patients (45.8%). For patients who underwent Sx + RT, local control at 3 and 5 years was 65.2% and 59.2%, respectively; for patients who received RT alone, local control at both 3 and 5 years was 22.7%. There were 12 late complications found in 8 patients: fistula formation (5 patients), trismus (3 patients), osteonecrosis (1 patient), retinopathy (1 patient), cellulitis (1 patient), and nasal stenosis (1 patient). CONCLUSIONS: The type of treatment to the primary site is an important determinant of disease free survival and local control. Failure at the primary site is the main problem in the curative treatment of patients with maxillary sinus carcinoma; efforts to improve survival in these patients should be directed toward improvement of local control.

Adult↗

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

Superficial hyperthermia and irradiation for recurrent breast carcinoma of the chest wall: prognostic factors in 196 tumors.

PURPOSE: To correlate patient-, tumor-, and treatment-related factors with subsequent local tumor control. METHODS AND MATERIALS: From 1977 to 1990, 196 subcutaneous/superficial lesions (179 measurable, 17 microscopic) in 151 patients with recurrent breast carcinoma of the chest wall were treated with superficial 915-MHz microwave hyperthermia and irradiation. The definition of min t43 > or = 10 min is that all monitored tumor catheters had a minimum of 1 hyperthermia session with temperatures > 43 degrees C for at least 10 min. RESULTS: Factors correlating with local control on univariate analysis included length of survival (> or = 1 year vs. < 1 year) (p < 0.0001), specific absorption rate (SAR) (> or = 25% vs. < 25%) (p = 0.0001), minimum t43 > 10 min (p < 0.0001), tumor volume (p < 0.0001), tumor surface area (p < 0.0001), tumor depth (p = 0.0002), number of hyperthermia sessions (p = 0.0003), and current radiation dose (p = 0.0012). On multivariate analysis, the factors best correlated with ultimate local control were SAR (p < 0.001) and number of hyperthermia sessions (p = 0.003). CONCLUSIONS: Multivariate analysis supports the importance of adequate specific absorption rate (SAR) coverage as a better predictor of local control than tumor volume, surface area, or depth. The explanation is that SAR can be correlated with the tumor surface area and depth, depending on the hyperthermia applicator characteristics. It is recommended that future clinical trials stratify study lesions into either SAR > or = 25% or < 25% because this can be readily estimated prior to initiating treatment. It is also recommended that future clinical trials attempt to have adequate lengths of follow-up after therapy to assess the results in long-term survivors.

Adult↗

PubMed1997

A randomized phase III study of accelerated hyperfractionation versus standard in patients with unresected brain metastases: a report of the Radiation Therapy Oncology Group (RTOG) 9104.

PURPOSE: To compare 1-year survival and acute toxicity rates between an accelerated hyperfractionated (AH) radiotherapy (1.6 Gy b.i.d.) to a total dose of 54.4 Gy vs. an accelerated fractionation (AF) of 30 Gy in 10 daily fractions in patients with unresected brain metastasis. METHODS AND MATERIALS: The Radiation Therapy Oncology Group (RTOG) accrued 445 patients to a Phase III comparison of accelerated hyperfractionation vs. standard fractionation from 1991 through 1995. All patients had histologic proof of malignancy at the primary site. Brain metastasis were measurable by CT or MRI scan and all patients had a Karnofsky performance score (KPS) of at least 70 and a neurologic function classification of 1 or 2. For AH, 32 Gy in 20 fractions over 10 treatment days (1.6 Gy twice daily) was delivered to the whole brain. A boost of 22.4 Gy in 14 fractions was delivered to each lesion with a 2-cm margin. RESULTS: The average age in both groups was 60 years; nearly two-thirds of all patients had lung primaries. Of the 429 eligible and analyzable patients, the median survival time was 4.5 months in both arms. The 1-year survival rate was 19% in the AF arm vs. 16% in the AH arm. No difference in median or 1-year survival was observed among patients with solitary metastasis between treatment arms. Recursive partitioning analysis (RPA) classes have previously been identified and patients with a KPS of 70 or more, a controlled primary tumor, less than 65 years of age, and brain metastases only (RPA class I), had a 1-year survival of 35% in the AF arm vs. 25% in the AH arm (p = 0.95). In a multivariate model, only age, KPS, extent of metastatic disease (intracranial metastases only vs. intra- and extracranial metastases), and status of primary (controlled vs. uncontrolled) were statistically significant (at p < 0.05). Treatment assignment was not statistically significant. Overall Grade III or IV toxicity was equivalent in both arms, and one fatal toxicity at 44 days secondary to cerebral edema was seen in the AH arm. CONCLUSION: Although a previous RTOG Phase I/II report had suggested a potential benefit in patients with limited metastatic disease, a good Karnofsky performance status, or neurologic function when treated with an AH regimen, this randomized comparison could not demonstrate any improvement in survival when compared to a conventional regimen of 30 Gy in 10 fractions. Therefore, this accelerated hyperfractionated regimen to 54.4 Gy cannot be recommended for patients with intracranial metastatic disease.

Adult↗

PubMed1997

Induction cisplatin/vinblastine and irradiation vs. irradiation in unresectable squamous cell lung cancer: failure patterns by cell type in RTOG 88-08/ECOG 4588. Radiation Therapy Oncology Group. Eastern Cooperative Oncology Group.

PURPOSE: To analyze disease failure patterns by pretreatment characteristics and treatment groups in a prospective randomized trial. METHODS AND MATERIALS: Patients with medically inoperable Stage II, unresectable IIIA and IIIB nonsmall cell lung cancer with KPS > or =70 and weight loss < or =5% were randomized to one of three treatment groups: standard radiation therapy with 60 Gy at 2.0 Gy per day (STD RT), induction chemotherapy with cisplatin 100 mg/m2 days 1 and 29 with vinblastine 5 mg/m2 weekly for 5 weeks followed by 60 Gy at 2.0 Gy per day (CT + RT), or hyperfractionated radiation therapy with 69.6 Gy at 1.2 Gy b.i.d. (HFX RT). Of 490 patients enrolled, 458 were evaluable. Minimum and median periods of observation for this analysis were 4 years and 6 years, respectively. RESULTS: Pretreatment characteristics were equally distributed. Toxicities were previously reported. Median survival rates were 11.4, 13.6, and 12.3 months for STD RT, CT + RT, and HFX RT, respectively (log rank p = 0.05, Wilcoxon p = 0.04). Survivals were 20, 31, and 24% at 2 years, and 4, 11, and 9% at 4 years in the STD RT, CT + RT, and HFX RT groups, respectively. There were no differences in local tumor control rates among the treatments. Patterns of first failure showed less distant metastasis (DM) (other than brain) for CT + RT compared to the RT alone arms (p = 0.04). Within squamous cell carcinoma (SCC), DM (other than brain) rates were 43%, 16%, and 38% in SCC for STD RT, CT + RT, and HFX RT, respectively (p = 0.0015). Patients with peripheral/chest wall lesions were significantly more likely to fail first in the thorax when treated on STD RT compared to CT + RT and HFX RT (p = 0.009). Survival rates were similar among the treatment arms for patients with squamous cell carcinoma. Among patients with nonsquamous cell carcinoma, failure patterns did not differ by treatment group, but survival was significantly better in those who were treated by induction chemotherapy (p = 0.04). CONCLUSION: Patients with squamous cell carcinoma treated on the CT + RT arm had a significant reduction of first DM other than brain, but there was difference in survival. Survival favored CT + RT in nonsquamous carcinoma despite similar failure patterns. Reasons for improved survival with CT + RT in NSCLC are not yet available.

Adenocarcinoma↗

PubMed1997

Clinical-severity staging system for oropharyngeal cancer: five-year survival rates.

OBJECTIVE: To improve the classification and survival estimates for patients with oropharyngeal cancer by combining cancer symptom severity and comorbidity with the current TNM cancer staging system. DESIGN: Retrospective medical record review using explicit coding criteria. SETTING: University medical center. PATIENTS AND METHODS: Two hundred ninety-six patients receiving initial treatment from January 1, 1980, to December 31, 1989. Multivariate analysis identified patient factors that had a significant impact on 5-year survival. These patient factors, symptom severity and comorbidity, were combined with cancer stage to create a composite clinical-severity staging system. MAIN OUTCOME MEASURE: Five-year survival. RESULTS: The overall 5-year survival rate was 38% (111/ 296). Survival by TNM cancer stage was 67% (18/27) for stage I, 46% (24/52) for stage II, 31% (26/85) for stage III, and 32% (43/132) for stage IV (chi2=10.84; P=.001). When patients were grouped according to the clinical-severity staging system, survival rates were 70% (16 of 23) for stage A, 47% (71 of 152) for stage B, 27% (18 of 67) for stage C, and 11% (6 of 54) for stage D (chi2=34.49; P=.001). CONCLUSIONS: Survival estimates can be improved by adding carefully studied and suitably defined patient variables to the TNM cancer stage. The current TNM cancer staging system for oropharyngeal cancer is based solely on the morphologic description of the tumor and disregards the clinical condition of the patient. Cancer symptom severity and comorbidity have a significant impact on survival. Continued exclusion of patient factors leads to imprecision in prognostic estimates and hinders interpretation of clinical studies.

Disease-Free Survival↗

PubMed1997

Radiation therapy for intrathoracic recurrence of non-small cell lung cancer.

Fifty-two of 2,315 patients (2.4%) with non-small cell lung cancer (NSLC) treated with radiation therapy at the Mallinckrodt Institute of Radiology and St. Luke's Hospital between 1975 and 1988 presented with local recurrence after definitive surgery. No patient received radiation therapy after surgery as part of initial treatment and none had evidence of distant metastases at the time of local recurrence. The median time to first recurrence was 14 months. At recurrence, patients presented with disease in the bronchial stump (eight patients), ipsilateral lung parenchyma (10), chest wall (six), regional lymph nodes (five), or some combination thereof (23). Sixty-five percent of patients had histologic evidence of recurrence. Radiation therapy consisted of > 5,000 cGy in conventional fractionation to areas of gross disease in 35 of 52 patients. Of 15 patients receiving > 6,000 cGy, 13 had a favorable--complete (CR) or partial (PR) response--tumor response to radiation therapy. Among these patients, local control was achieved in 70% of patients with marginal recurrences (i.e., stump, parenchyma, or chest wall) and in 50% with nodal recurrences. The median survival after radiation therapy for all patients was 8.5 months. The best indicators for long-term survival were the interval from initial surgery to first recurrence and tumor response to radiation therapy.

Carcinoma, Non-Small-Cell Lung↗

PubMed1997

Impact of adding concurrent chemotherapy to hyperfractionated radiotherapy for locally advanced non-small cell lung cancer (NSCLC): comparison of RTOG 83-11 and RTOG 91-06.

A hyperfractionated radiation therapy (HFX RT) trial (1.2 Gy twice daily, b.i.d.) (HFX) for non-small cell lung cancer (NSCLC) showed that 69.6 Gy resulted in better survival than did lower total doses (Radiation Therapy Oncology Group, RTOG 83-11) and that cisplatin concurrent with irradiation improved local control and survival over RT alone (Radiation Therapy Oncology Group, RTOG 91-06). Concurrent combination chemotherapy and HFX could improve both local and systemic control. In a phase II trial (RTOG 91-06) for inoperable NSCLC, two cycles of PE were used [cisplatin 50 mg/m2 intravenously (i.v.) days 1 and 8, etoposide 50 mg orally (p.o.) b.i.d., 75 mg/day if body surface area (BSA) < 1.7 m2, days 1-14] starting on day 1 of HFX (69.6 Gy) and repeated on day 29. HFX/PE was compared with HFX (69.6 Gy) from an earlier phase II trial (RTOG 83-11). Seventy-six patients treated with HFX/PE and 203 patients who received HFX alone were compared for toxicity, response, survival, and patterns of failure. The rates of grade 4 nonhematologic toxicity were similar (3.0% for HFX/PE, 3.0% for HFX), but grade 4 hematologic toxicity occurred only with HFX/PE 56.6%. Three (3.9%) HFX/PE patients had fatal toxicity (2 pulmonary, 1 renal); 1 HFX patient had fatal esophageal toxicity. Response and metastasis rates were similar for the two treatments, but infield (p = 0.054) and overall (p = 0.04) progression-free survival rates were better with HFX/PE. Median survivals were 18.9 months with HFX/PE and 10.6 months with HFX. Two-year survival rates were 36% for HFX/PE and 22% for HFX (p = 0.014). The differences in survival between HFX/PE and HFX remained borderline statistically significant (p = 0.0593) in the multivariate model, which included weight loss, Karnofsky performance status (KPS), sex, and stage. HFX/PE is an effective regimen in patients with inoperable NSCLC, although it is considerably more toxic, and is undergoing a comparison in a three-arm randomized phase III study against induction cisplatin/vinblastine plus standard once-daily RT and against cisplatin/vinblastine concurrent with standard RT.

Administration, Oral↗

PubMed1997

Postoperative radiation therapy in non-small cell lung cancer.

One hundred seventy-three patients with the diagnosis of non-small cell lung cancer (NSCLC) were treated with surgery and postoperative radiation therapy (RT) at the Radiation Oncology Center, Washington University, St. Louis. All patients had been retrospectively reviewed and restaged according to the new American Joint Committee (AJC) staging classification. Seventeen patients were stage I, 69 were stage II, 74 were stage IIIA, and 2 patients were stage IIIB. In 11 patients, accurate staging could not be determined. Indications for postoperative RT were positive surgical margins (32 patients), metastatic hilar nodes (78 patients), and metastatic mediastinal nodes (62 patients). Locoregional control for stages I, II, and IIIA was 85, 75, and 85%, respectively. Five-year actuarial survival was 35% for stage I and 20% for stages II and IIIA. Patients with N0 disease (positive margins) had 5-year survival of 25%, whereas patients with N1 and N2 disease had a 5-year survival of 20%.

Adenocarcinoma↗

PubMed1997

Progress report of combined chemoradiotherapy versus radiotherapy alone in patients with esophageal cancer: an intergroup study.

PURPOSE: The present intergroup phase III randomized study compared combined chemotherapy (CT) plus radiotherapy (RT) treatment versus RT only in patients with locally advanced esophageal cancer. MATERIALS AND METHODS: Two courses of chemotherapy during 50 Gy RT followed by additional two courses of the same CT, versus 64 Gy RT alone were investigated. CT consisted of cisplatin 75 mg/m2 on day 1 [corrected] and fluorouracil (5FU) 1,000 mg/m2/d on days 1 to 4 every 4 weeks with RT and every 3 weeks post-RT. The main objective of the study was to compare overall survival between the two randomized treatment groups. Patients were stratified by tumor size, histology, and degree of weight loss. RESULTS: Sixty-two assessable patients were randomized to receive RT alone, and 61 to the combined arm. Patients characteristics were as follows: squamous cell cancer, 90% versus 85%; weight loss greater than 10 lb, 61% versus 69%; and tumor size, > or = 5 cm, 82% versus 80% on the RT and CT-RT arms, respectively. Systemic side effects, which consisted of nausea, vomiting, and renal and myelosuppression, occurred more frequently on the combined arm, while local side effects were similar in both groups. With a minimum follow-up time of 5 years for all patients, the median survival duration was 14.1 months and the 5-year survival rate was 27% in the combined treatment group, while the median survival duration was 9.3 months with no patients alive at 5 years in the RT-alone group (P < .0001). Additional patients (69) were treated with the same combined therapy and were analyzed. The results of the last group confirmed all of the results obtained with combined CT-RT in the randomized trial, with a median survival duration of 17.2 months and 3-year survival rate of 30%. CONCLUSION: We conclude that cisplatin and 5FU infusion given during and post-RT of 50 Gy is statistically superior to standard 64-Gy RT alone in patients with locally advanced esophageal cancer.

Adult↗

PubMed1996

Results of a trial with topotecan dose escalation and concurrent thoracic radiation therapy for locally advanced, inoperable nonsmall cell lung cancer.

PURPOSE: To conduct a dose escalation clinical study with topotecan and concurrent standard dose thoracic irradiation to assess its feasibility and toxicity in the treatment of patients with locally advanced, inoperable nonsmall cell lung cancer (NSCLCA). METHODS AND MATERIALS: Between April 1993 and August 1994, 12 patients with inoperable, loco-regionally advanced NSCLCA were entered in a prospective dose escalation trial and assigned to receive concurrent thoracic radiotherapy and topotecan. Patients received thoracic irradiation to a total tumor dose of 60 Gy in 30 fractions. Initial fields were to encompass the gross disease plus the mediastinum. Topotecan was delivered by bolus injection days 1 through 5, and days 22 through 26, beginning on the same day as the radiation therapy. The initial dose level was 0.5 mg/m2. Two additional dose levels of 0.75 mg/m2 and 1.0 mg/m2 were tested. RESULTS: Six patients were accessioned to the 0.5 mg/m2 dose level, three patients to the 0.75 mg/m2 dose level, and three patients to the 1.0 mg/m2 dose level. At the 0.5 mg/m2 dose level, zero of six patients had > or = Grade 4 hematologic toxicity. One of the six had Grade 3 esophagitis. At the 0.75 mg/m2 dose level, two of three patients had > or = Grade 3 nonhematologic toxicity including anorexia, fatigue, nausea, vomiting, and weakness; zero patients experienced > or = Grade 4 hematologic toxicity. At the 1.0 mg/m2 dose level one of three patients had > or = Grade 3 esophagitis, and two of three patients experienced Grade 4 neutropenia. With a follow-up of 12 to 24 months, two patients are alive and free of disease, three patients are alive with disease (two with distant metastasis, one with local disease and distant metastasis), and the remaining seven patients are dead of disease. CONCLUSIONS: The combination of topotecan and thoracic radiotherapy for nonsmall lung cancer, in the manner given by this protocol, could be safely given at a dose level of only 0.5 mg/m2 days 1 to 5 and 22 to 26 with 60 Gy of external beam radiotherapy. Higher doses of topotecan were associated with high hematologic and gastrointestinal toxicity. Distant metastasis was the primary pattern of failure.

Aged↗

PubMed1996

The impact of surgical margin status and use of an interstitial implant on T1, T2 oral tongue cancers after surgery.

PURPOSE: In patients with T1,T2 oral tongue carcinoma treated with surgical resection, postoperative radiation therapy (RT) is required especially when surgical margins contain tumors. Irradiation techniques include external beam, interstitial implants, or a combination of the two modalities. We investigated whether positive surgical margin remains a poor prognostic factor after radiation therapy, and the contribution of interstitial implants to disease control. METHODS AND MATERIALS: Between 1972 and 1989, 55 patients were treated postoperatively at the Mallinckrodt Institute of Radiology for T1,T2 squamous cell carcinomas of the oral tongue. Surgeries included 26 wide excisions or excisional biopsies and 29 composite resections or hemiglossectomies. Thirty-nine patients received external radiation therapy alone and 16 patients had an interstitial implant (ISI) as part of the treatment. The minimum follow-up is 4 years. RESULTS: At 2 and 5 years, the overall survivals for all patients were 82 and 68%. The disease-free survivals (DFS) were 82 and 70%, respectively. There was no significant difference in the pattern of failure and DFS when stratified by the status of surgical margins and the type of the surgical procedure. Local control was achieved in 15 of 18 patients when surgical margins were involved by tumor and in 29 of 37 patients without tumor involving margins (p > 0.05). Ten of 18 (56%) patients with tumor involving resection margins were treated with ISI, whereas only 3 of 33 (9%) of those with negative margins received ISI. Local control was achieved in 32 of 39 patients treated with external beam RT alone, and 13 of 16 patients who received interstitial implant (p > 0.05). Four patients treated with ISI developed persistent soft tissue ulceration and mandibular bone exposures. CONCLUSIONS: Postoperative radiation therapy converted the ominous outcome of patients with tumor involving surgical margins. Patients with positive surgical margins were often selected to be treated with interstitial implants. We found that the local control was as good as in those with a more favorable pathology (negative margins) and treated with external RT alone. Further investigation is needed to optimize the implant treatment to minimize the complications.

Adult↗

PubMed1996

Prognostic significance of clinical factors and p53 expression in patients with glottic carcinoma treated with radiation therapy.

BACKGROUND: Numerous clinical parameters have been suggested as predictors of outcome for patients with head and neck carcinoma treated with radiation therapy, but their applicability remains controversial. Inactivation of the p53 tumor suppressor results in radioresistance in experimental systems and might predict treatment failure in human patients. We have tested this hypothesis by comparing the predictive power of nuclear accumulation of p53 protein with that of clinical and histopathologic markers in patients with glottic carcinoma treated with primary radiotherapy. METHODS: Clinical charts were reviewed for 165 patients with glottic squamous cell carcinoma treated with radiation therapy. One hundred and twenty-one patients with T1 or T2 classified tumors were determined to have received adequate treatment and to have adequate follow-up data for further study. Archival pretreatment tumor biopsies from a subpopulation of patients were examined for p53 protein by immunohistochemistry. The influence of clinical and histopathologic variables and p53 nuclear protein on tumor recurrence was studied by bivariate and multivariate analysis. RESULTS: The recurrence rate was lowest for patients with moderately to poorly differentiated tumors (P < 0.05). This was the only significant predictor of outcome in this patient population. The presence of immunohistochemically detectable p53 antigen was not predictive of tumor recurrence in 70 patients for whom there was both p53 and sufficient follow-up data. CONCLUSIONS: Histologic differentiation was prognostic for tumor recurrence in this population of patients with glottic carcinoma treated with radiation therapy. In contrast, nuclear accumulation of p53 protein was not predictive of tumor response or recurrence in this population.

Aged↗

PubMed1996

Recursive partitioning analysis of 2105 patients treated in Radiation Therapy Oncology Group studies of head and neck cancer.

BACKGROUND: The Radiation Therapy Oncology Group conducts large-scale prospective, randomized trials to test new concepts in cancer patient care and provide information about pretreatment and treatment factors that may influence outcome. METHODS: Recursive partitioning analysis (RPA) was used to examine the data derived from 2105 patients. RPA grouped patients according to the influence of tumor, of host, and of treatment variables on outcome. RESULTS: For survival, the most important factor was T classification. For lesions less than T3, the primary tumor was the next most important factor, whereas for T3 and T4 lesions the Karnofsky score was the next most predictive factor. Six distinct groups were formed by RPA, with median survivals ranging from 6.8 to 151.8 months. For local-regional control, the N classification was the most important factor. For patients with no adenopathy, T classification was the next most important factor, whereas for patients with adenopathy, the number of treatment fractions was the next most important factor. Such analysis created 5 distinct groups. In the most favorable, the median time to local-regional relapse has not yet been reached. In the least favorable group, fewer than 50% of the patients experienced complete response at any time following treatment. CONCLUSIONS: RPA clarifies the relative importance and potential interactions of pretreatment and treatment variables and should permit more accurate stratification of patients in future trials.

Carcinoma, Squamous Cell↗