Showing papers by "Barbara Fisher published in 1997"

Supratentorial low-grade glioma in adults: an analysis of prognostic factors and timing of radiation.

Abstract: PURPOSETo review the outcomes of patients with low-grade glioma diagnosed by modern imaging and treated at a center where postponing radiotherapy was common practice.METHODSWe reviewed the records of patients (age > or = 18 years) with pathologically confirmed supratentorial low-grade fibrillary astrocytoma, oligodendroglioma, and mixed glioma treated at a regional cancer center in Canada between 1979 and 1995.RESULTSMedian survival for the entire group (N = 167; mean age 40.6 years) was 10.5 years with 5- and 10-year survival rates of 72% and 50%, respectively. Median progression-free survival was 4.9 years with 5- and 10-year progression-free rates of 50% and 12%, respectively. Overall and progression-free survivals were longer for patients with an oligodendroglioma or mixed glioma than with astrocytoma (median 13 v 7.5 years, P = .003; progression-free 5.6 v 4.4 years, p = .054). Age at diagnosis < or = 40 years, seizures at presentation, minimal residual tumor after surgery, Karnofsky performance stat...

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

Abstract: 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 ≥ 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 ≥ 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. Also, concurrent ChT/hyperfractionated RT, and induction ChT followed by concurrent ChT/standard RT, appear to have a benefit in terms of increased tumor response compared to sequential ChT/RT, but not in failure pattern. The latter may reflect the presence of pretherapy micrometastases that are delayed from progression by the combined therapy, but not prevented.

Extracapsular axillary node extension in patients receiving adjuvant systemic therapy: an indication for radiotherapy?

Abstract: Purpose This is a retrospective review into the patterns of failure of 82 patients with Stage II or III breast cancer who had extracapsular extension (ECE) of axillary nodal metastases and who received systemic chemotherapy or hormonal therapy without loco-regional radiation. Methods and materials The clinical records of patients with axillary node positive (T1-T3, N1, 2) Stage II or III breast cancer seen at the London Regional Cancer Centre between 1980-1989 were reviewed. Patients were identified who underwent segmental mastectomy with axillary node dissection or modified radical mastectomy and received adjuvant chemotherapy or tamoxifen but did not undergo loco-regional radiation. Eighty-two patients within this group had pathologic evidence of extracapsular axillary node extension (ECE). For 45 of these patients the extension was extensive, and for the remaining 37 it was microscopic. This ECE-positive group was compared to a subgroup of 172 patients who did not have pathologic evidence of extracapsular axillary node extension but had metastatic carcinoma confined within the nodal capsule. Results Median age of the 82 ECE-positive patients was 56 years. Twenty-five patients had had a segmental mastectomy, the remainder a modified radical mastectomy. Median actuarial survival was 60 months, with a median disease-free and loco-regional failure-free survival of 38 months. Seventy-eight percent of these patients developed a recurrence, which was loco-regional in 60% (21% local, 21% regional, 2% local and regional, and 16% loco-regional and metastatic). There was a 36% recurrence rate in intact breast, 14% the chest wall following modified radical mastectomy, 7% relapsed in the axilla, 12% in supraclavicular nodes, and 1% in the internal mammary nodes. A comparison of the 82 ECE-positive patients with a group of 172 ECE-negative patients determined that there was a statistically significant difference between the two groups in terms of survival (overall and disease-free) and loco-regional recurrence. Univariate analysis of the entire 254 node-positive patient group revealed extracapsular nodal extension (ECE) to be a prognostically significant factor for actuarial and disease-free survival as well as for loco-regional failure, but ECE did not remain an independently prognostic factor after multivariate analysis. Segmental mastectomy, positive resection margins, and ER negative status increased the risk of loco-regional recurrence within the ECE-positive group. Conclusions Extracapsular axillary node extension is a prognostically significant factor for actuarial survival, disease-free survival, and loco-regional failure but not independent of other adverse prognostic factors. It is a marker for increased loco-regional recurrence associated with doubling of breast, chest wall, and supraclavicular recurrence rates. The risk of axillary relapse in patients who have had an adequate level I and II axillary dissection but demonstrate extracapsular extension is low (7%). We recommend breast/chest wall and supraclavicular radiation for all patients with pathologic evidence of such extranodal extension who have had a level I and II axillary dissection regardless of the number of positive axillary nodes. Axillary irradiation should be considered for patients who have had only an axillary sampling or level I axillary dissection.

Strong correlation between imaging response and survival among patients with primary central nervous system lymphoma: a secondary analysis of RTOG studies 83-15 and 88-06

Abstract: Purpose: Primary central nervous system lymphoma (PCNSL) is the brain tumor with the most rapidly increasing incidence, yet little is known about its radiographic response to cranial irradiation. If traditionally used doses of radiotherapy (∼60 Gy) are associated with low rates of complete response and poor survival, then an argument can be made to consider dose escalation of radiotherapy. Alternatively, if poor survival rates are associated with high rates of complete response, there would be no reason to subject patients to higher radiation doses with increased risks of treatment-related morbidity. The purpose of this analysis is to provide a detailed review of response following cranial irradiation. Based on these findings, recommendations are offered for future protocol design. Methods and Materials: Patients were treated on either RTOG 83-15 (whole brain irradiation to 40 Gy followed by a 20 Gy boost to the tumor plus 2-cm margin) or RTOG 88-06 (induction cyclophosphamide, doxorubicin, vincristine, dexamethasone [CHOD] followed by whole brain irradiation to 41.4 Gy and an 18 Gy tumor boost). Imaging surveillance (CT, MR) was required following surgery, prior to the initiation of RT and following completion of RT. Complete response referred to the absence of enhancement on follow-up scans in comparison to the pretherapy study. A tumor size reduction of at least 50% in the product of the largest cross-sectional diameter and its largest perpendicular diameter was scored as a partial response. Results: Seventy-nine patients had scans available for central review. Complete response was achieved in 83% and 85% of patients treated on RTOG 83-15 and 88-06, respectively. The rates of partial response (14%, 11%) and radiographic progression (3%, 4%) also were comparable between the studies. For survival analyses, data were aggregated from the two studies. The 4-year survival rates were 24% for complete responders versus 11% for other patients ( p = 0.0006). In multivariate analysis, only complete radiographic response ( p p Conclusion: A high rate of complete radiographic response was observed following moderate doses of cranial irradiation (alone or in combination with CHOD chemotherapy). Although complete responders had a statistically significant survival advantage at 4 years when compared with partial responders and nonresponders, the majority of patients who achieved complete response were dead of disease by 4 years following treatment. Based on this analysis of the RTOG database, there is no rationale for radiation dose escalation as a therapeutic strategy to combat PCNSL. Consequently, the radiotherapy component of the current RTOG Phase II trial (RTOG 93-10) now includes relatively low total doses of hyperfractionated irradiation for patients without residual disease (36 Gy/1.2 Gy, twice a day) as well as a more aggressive chemotherapy regimen.

A Phase I pilot study of pelvic radiation and alpha-2a interferon in patients with locally advanced or recurrent rectal cancer

Abstract: Purpose : The purpose of this pilot study was to determine the maximum tolerated dose at alpha-2a interferon given by subcutaneous injection and combined with high dose pelvic radiation for locally advanced or recurrent rectal cancer. Methods and Materials : In this Phase I pilot study, patients with local advancd, unresectable, or recurrent rectal cancer with or without distant metastases received external beam pelvic radiotherapy over 5 to 6 weeks combined with escalating doses of alpha-2a interferon. Interferon was escalated in increments of 3 million units for each patient cohort, starting at 3 million units subcutaneously 3 days weekly during pelvic radiation. Radiotherapy consisted of 4 Gy (2 Gy fractions) to the pelvic followed by a boost of 6 Gy or 16 Gy to gross pelvic tumor, depending on the presence or absence of small bowel in the boost field, respectively. Between 1991 and 1993, 10 patients were treated on this study, five with locally advanced and five with locally recurrent rectal cancer. Results: At 6 million units of interferon, Grade 3 (WHO criteria) toxicities were as follows: diarrhea (one), leukopenia (one), and neutropenia (one). One patient died of a massive GI bleed at this dose level. Death was not felt to be treatment related. The maximum tolerated dose of interferon was 3 million units three times weekly with radiation. Three patients had unusual complications at 4, 6, and 6 months possibly related to treatment. The first had a right distal ureteric stricture with a right urinoma. The second had a sudden left foot drop that has remaind stable. The third had sudden onset of bilateral lower extremity paraplegia with spontaneous resolution. Conclusions : The maximally tolerated dose of interferon alpha-2a given three times weekly during pelvic radiation was 3 million units based on acute side effects. Nevertheless, even at this dose level there were three unusual subacute complications possibly related to treatment. Caution is advised when combining interferon alpha-2a with high dose pelvic radiation, especially in patients with predisposing conditions (such as diabetes) for radiotherapy complications.