Early-stage mantle cell lymphoma: a retrospective analysis from the International Lymphoma Radiation Oncology Group (ILROG).

BACKGROUND: Mantle cell lymphoma (MCL) rarely presents as early-stage disease, but clinical observations suggest that patients who present with early-stage disease may have better outcomes than those with advanced-stage disease. PATIENTS AND METHODS: In this 13-institution study, we examined outcomes among 179 patients with early-stage (stage I or II) MCL in an attempt to identify prognostic factors that influence treatment selection and outcome. Variables examined included clinical characteristics, treatment modality, response to therapy, sites of failure, and survival. RESULTS: Patients were predominantly male (78%) with head and neck being the most common presenting sites (75%). Most failures occurred outside the original disease site (79%). Although the administration of radiation therapy, either alone or with chemotherapy, reduced the risk of local failure, it did not translate into an improved freedom from progression or overall survival (OS). The treatment outcomes were independent of treatment modality. The 10-year OS for patients treated with chemotherapy alone, chemo-radiation therapy and radiation therapy alone were 69%, 62%, and 74% (P = 0.79), and the 10-year freedom from progression were 46%, 43%, and 31% (P = 0.64), respectively. CONCLUSION: Given the excellent OS rates regardless of initial therapy in patients with early-stage MCL, de-intensified therapy to limit treatment-related toxicity is a reasonable approach.

Osseous Pseudoprogression in Vertebral Bodies Treated with Stereotactic Radiosurgery: A Secondary Analysis of Prospective Phase I/II Clinical Trials.

BACKGROUND AND PURPOSE: Osseous pseudoprogression on MR imaging can mimic true progression in lesions treated with spine stereotactic radiosurgery. Our aim was to describe the prevalence and time course of osseous pseudoprogression to assist radiologists in the assessment of patients after spine stereotactic radiosurgery. MATERIALS AND METHODS: A secondary analysis of 2 prospective trials was performed. MRIs before and after spine stereotactic radiosurgery were assessed for response. "Osseous pseudoprogression" was defined as transient growth in signal abnormality centered at the lesion with a sustained decline on follow-up MR imaging that was not attributable to chemotherapy. RESULTS: From the initial set of 223 patients, 37 lesions in 36 patients met the inclusion criteria and were selected for secondary analysis. Five of the 37 lesions (14%) demonstrated osseous pseudoprogression, and 9 demonstrated progressive disease. There was a significant association between single-fraction therapy and the development of osseous pseudoprogression (P = .01), and there was a significant difference in osseous pseudoprogression-free survival between single- and multifraction regimens (P = .005). In lesions demonstrating osseous pseudoprogression, time-to-peak size occurred between 9.7 and 24.4 weeks after spine stereotactic radiosurgery (mean, 13.9 weeks; 95% CI, 8.6-19.1 weeks). The peak lesion size was between 4 and 10 mm larger than baseline. Most lesions returned to baseline size between 23 and 52.4 weeks following spine stereotactic radiosurgery. CONCLUSIONS: Progression on MR imaging performed between 3 and 6 months following spine stereotactic radiosurgery should be treated with caution because osseous pseudoprogression may be seen in more than one-third of these lesions. Single-fraction spine stereotactic radiosurgery may be associated with osseous pseudoprogression. The possibility of osseous pseudoprogression should be incorporated into the prospective criteria for assessment of local control following spine stereotactic radiosurgery.

Nucleotide excision repair proteins and their importance for radiation-enhanced transfection.

PURPOSE: Irradiated cells transfect more efficiently than unirradiated cells because of a radiation-induced increase in plasmid integration. However, the molecular mechanism is unclear. Because of recent observations that nucleotide excision repair (NER) proteins can be involved in certain types of recombination in yeast, it was hypothesized that NER proteins might play a role in this radiation-enhanced integration. MATERIALS AND METHODS: Hamster and human cells with inactivating mutations in NER genes were irradiated at doses from 0 to 6 Gy and then immediately transfected with a linearized selectable marker plasmid. Transfection-enhancement ratios (TERs) were calculated as the ratio of the number of drug-resistant colonies in unirradiated cells to the number of transfectants in irradiated cells, corrected for cytotoxicity from radiation. RESULTS: Transfection into unirradiated rodent cells was unaffected by NER mutation status. Transfection into unirradiated human cells, however, was increased by NER mutation. The TERs were 5 and 100 for CHO and primary human fibroblasts, respectively, after exposure of the cells to 6 Gy. Mutations in ERCC1, XPA, XPB, XPC, XPF, XPG and CSB dramatically reduced TER. Mutations in ERCC1, XPC, XPF, XPG and CSB suppressed transfection so that the TER was significantly below 1. CONCLUSIONS: The mechanism of radiation-enhanced plasmid integration was distinct from that of plasmid integration in unirradiated cells, and NER gene products were critical for enhanced integration to occur.

High-dose-rate endobronchial brachytherapy effectively palliates symptoms due to airway tumors: the 10-year M. D. Anderson cancer center experience.

PURPOSE: To evaluate the toxicity and efficacy of Iridium-192 high-dose-rate (HDR) endobronchial brachytherapy (EBBT) for the palliation of symptoms caused by relapsed or persistent endobronchial tumors. METHODS AND MATERIALS: We reviewed the treatment outcomes between 1988 and 1997 in 175 lung cancer patients who underwent HDR EBBT for recurrent or metastatic tumors at The University of Texas M. D. Anderson Cancer Center. One hundred sixty of these patients had previously received thoracic external-beam irradiation. This updated report includes 74 patients from a previous series. Most patients received 3,000-cGy EBBT delivered at a distance of 6 mm and divided into 2 fractions over 2 weeks. Subjective response was assessed by questionnaire at follow-up. Objective response was assessed by physical examination, bronchoscopy, and chest radiograph. RESULTS: The median actuarial survival for the entire group was 6 months from the time of the first EBBT treatment session. Of the 115 patients (66%) who showed symptomatic improvement, 32% were much improved and 34% were slightly improved. Patients showing improvement survived for significantly longer than those who showed no change or worsening symptoms (7 vs. 4 months, p = 0.0032). Repeat bronchoscopy demonstrated a 78% overall objective response rate that correlated significantly with subjective response and symptom relief. Complications occurred in 19 patients (11% crude rate) with an actuarial complication rate of 13% at 1 year from the time of the first EBBT treatment session. The actuarial hazard for fatal hemoptysis due to EBBT was 5%. CONCLUSION: HDR EBBT effectively palliates most patients' symptoms caused by endobronchial lesions. This relief correlates significantly with an overall survival benefit. Treatment complications appear to be few, even for patients who have received prior external-beam irradiation.

Agreement rates among single photon emission computed tomography using gallium-67, computed axial tomography and lymphangiography for Hodgkin disease and correlation of image findings with clinical outcome.

BACKGROUND: This study was undertaken to systematically evaluate the agreement rates among single photon emission computed tomography using gallium-67 (Ga-67 SPECT), lymphangiography (LAG), and computed axial tomography (CT) scan findings for Hodgkin disease and to correlate radiologic findings with clinical outcome. METHODS: One hundred three previously untreated patients with Hodgkin disease who had Ga-67 SPECT scan between August 1992 and December 1994 at our institution form the basis of this study. The agreement rates among Ga-67 SPECT, LAG, and CT scan findings were calculated by sites from the pretreatment evaluation throughout the courses of chemotherapy. The probabilities of recurrence or progression by sites were correlated with the radiologic findings. RESULTS: The median follow-up was 3 years. The pretreatment agreement ranged from 75% to 100% between Ga-67 SPECT and CT scans, 85-100% between CT scan and LAG, and 74-99% between Ga-67 SPECT and LAG. A greater variation in agreement was observed once chemotherapy was started, the site with the least agreement being the mediastinum. The most common site of the recurrence or progression was also the mediastinum. When the CT scan showed persistent abnormality even after Ga-67 SPECT turned negative after chemotherapy, the chances of mediastinal recurrence or progression were 3 in 34 and 3 in 18 after 1-3 cycles and 4-6 cycles, respectively. CONCLUSIONS: Although there was a relatively high correlation between Ga-67 SPECT and the other modalities, the intrinsic limitation of planar Ga-67 was still observed in Ga-67 SPECT especially in the mediastinum. There was still a moderate risk of mediastinal recurrence or progression even after residual CT scan abnormality lost gallium avidity from chemotherapy.

Locoregional irradiation for inflammatory breast cancer: effectiveness of dose escalation in decreasing recurrence.

PURPOSE: To evaluate the effect of radiation dose escalation on locoregional control, overall survival, and long-term complication in patients with inflammatory breast cancer. PATIENTS AND METHODS: From September 1977 to December 1993, 115 patients with nonmetastatic inflammatory breast cancer were treated with curative intent at The University of Texas M. D. Anderson Cancer Center. The usual sequence of multimodal treatment consisted of induction FAC or FACVP chemotherapy, mastectomy (if the tumor was operable), further chemotherapy, and radiation therapy to the chest wall and draining lymphatics. Sixty-one patients treated from September 1977 to September 1985 received a maximal radiation dose of 60 Gy to the chest wall and 45-50 Gy to the regional lymph nodes, 22 treated once a day at 2 Gy per fraction, and 35 were treated b.i.d. (32 after mastectomy and all chemotherapy was completed, and 2 immediately after mastectomy; one patient had distant metastases discovered during b.i.d. irradiation, and treatment was stopped). Four additional patients received preoperative radiation with standard fractionation. Based on the analysis of the failure patterns of the patients, the dose was increased for the b.i.d. patients in the new series, with 51 Gy delivered to the chest wall and regional nodes, followed by a 15-Gy boost to the chest wall with electrons. From January 1986 to December 1993, 39 patients were treated b.i.d. to this higher dose after mastectomy and all the chemotherapy was completed; and 8 additional patients received preoperative irradiation with b.i.d. fractionation to 51 Gy. During this period, another 7 patients were treated using standard daily doses of 2 Gy per fraction to a total of 60 Gy, either because they had a complete response or minimal residual disease at mastectomy or because their work schedule did not permit the b.i.d. regimen. Comparison was made between the groups for locoregional control, disease-free and overall survival, and complication rates. RESULTS: The median follow-up time was 5.7 years (range, 1.8-17.6 years). For the entire patient group, the 5- and 10-year local control rates were 73.2% and 67.1%, respectively. The 5- and 10-year disease-free survival rates were 32.0% and 28.8%, respectively, and the overall survival rates for the entire group were 40.5% and 31.3%, respectively. To evaluate the effectiveness of dose escalation, a specific comparison of patients who received b.i.d. radiation after mastectomy and completion of adjuvant chemotherapy was performed. There were 32 patients treated b.i.d. to 60 Gy in the old series versus 39 patients treated b.i.d. to 66 Gy in the new series. There was an significant improvement in the rate of locoregional control for the b.i.d. patients for the old vs. new series, from 57.8% to 84.3% and from 57.8% to 77.0% (p = 0.028) at 5 and 10 years, respectively. Chemotherapy regimens did not change significantly during this time period.Long-term complications of radiation, such as arm edema more than 3 cm (7 patients), rib fracture (10 patients), severe chest wall fibrosis (4 patients), and symptomatic pneumonitis (5 patients), were comparable in the two groups, indicating that the dose escalation did not result in increased morbidity. Significant differences in the rates of locoregional control (p = 0.03) and overall survival (p = 0.03), and a trend of better disease-free survival (p = 0.06) were also observed that favored the recently treated patients receiving the higher doses of irradiation. CONCLUSION: Twice-daily postmastectomy radiation to a total of 66 Gy for patients with inflammatory breast cancer resulted in improved locoregional control, disease free survival, and overall survival, and was well tolerated.

Prognostic implications of response to preoperative infusional chemoradiation in locally advanced rectal cancer.

BACKGROUND AND PURPOSE: To evaluate the influence of response to preoperative infusional chemoradiation on outcome parameters among patients with locally advanced rectal cancer. MATERIALS AND METHODS: Preoperative chemoradiotherapy, 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-fluorouracil (300 mg/m2 per day), was given to 117 patients. As determined by pretreatment endorectal ultrasound (EUS), 96% of cases were Stage T3, and 51% had EUS evidence of perirectal adenopathy. Surgery was performed approximately 6 weeks after chemoradiation therapy. Postoperatively adjuvant systemic therapy, consisting of 400-425 mg/m2 of 5-fluorouracil plus 20 mg/m2 leucovorin for 5 days, was administered every 28 days for six cycles. Outcome parameters of local control (LC), freedom from distant metastases (DMC), disease-free survival (DFS) and cancer specific survival (CSS) were evaluated relative to primary tumor characteristics. RESULTS: The final post-treatment pathological tumor stages were complete response in 27%, Tis-2 N0 in 26%, T2 N1 in 5%, T3 N0 in 21%, T3 N1 in 15%, T4 N0 in 5% and T4 N1 in 1%. Down-staging occurred in 61% of cases. The pretreatment primary tumor size only influenced rates of local control (P < 0.03) and had no other influence on outcome parameters. Pretreatment evidence of perirectal lymph node involvement had no impact on outcome parameters. Pathologic evidence of nodal involvement did affect DMC (P < 0.002) and DFS (P < 0.003). Pathologic evidence of response did influence freedom from the development of distant metastases (P < 0.004). On pairwise analysis this relationship held only when responders were compared to non-responders. No difference was observed based on the level of downstaging at the primary tumor. Correspondingly, DFS was improved when non-responders were compared to downstaged patients (P < 0.01). Response to preoperative chemoradiation failed to affect rates of LC or CSS. For the group as a whole, adjuvant chemotherapy improved only CSS (P < 0.03). Adjuvant chemotherapy was given to 74 patients, 36 of whom had responded to preoperative chemoradiation. Improvements were only seen in DFS (P < 0.03) when down-staged patients were compared to the non-responders who received adjuvant chemotherapy. In addition, the DFS rates were lower in the non-responder group who received adjuvant chemotherapy even when they were compared to down-staged patients who did not receive adjuvant chemotherapy (P < 0.04). CONCLUSION: Consistent with other reports, disease free survival and subsequent development of distant metastases is reduced in the more than 60% of patients who respond to preoperative infusional chemoradiation. Evidence of response appears more significant than the degree of response. At present, no impact is seen on cancer specific survival rates. Consideration should be given for strategies that base selection of subsequent adjuvant chemotherapy on response to preoperative chemoradiation.

Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience.

PURPOSE: To evaluate the rates of tumor downstaging after preoperative chemoradiation for locally advanced rectal cancer. MATERIALS AND METHODS: Preoperative chemoradiotherapy (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-fluorouracil (300 mg/m2/day) was given to 117 patients. The pretreatment stage distribution, as determined by endorectal ultrasound (u), included uT2N0 in 2%, uT3N0 in 47%, uT3N1 in 49%, and uT4N0 in 2% of cases; endorectal ultrasound was not performed in 13% of cases (15 patients). Approximately 6 weeks after completion of CTX/XRT, surgery was performed. RESULTS: The pathological tumor stages were Tis-2N0 in 26%, T2N1 in 5%, T3N0 in 21%, T3N1 in 15%, T4N0 in 5%, and T4NI in 1%; a complete response (CR) to preoperative CTX/XRT was pathologically confirmed in 32 (27%) of patients. Tumor downstaging occurred in 72 (62%) cases. Only 3% of cases had pathologic evidence of progressive disease. Pretreatment tumor size (< 5 cm vs. > or = 5 cm) was the only factor predictive of tumor downstaging (p < 0.04). A decrease of > 1 T-stage level was accomplished in 45% of those downstaged. Overall, a sphincter-saving (SP) procedure was possible in 59% of patients and an abdominoperineal resection (APR) was required in 41 % of cases. Factors predictive of SP included downstaging (p < 0.03), age > 40 years (p < 0.007), pretreatment tumor distance, 3 to 6 cm from the anal verge (p < 0.00001), tumor size <6 cm (p < 0.02), mobility (p < 0.004), tumor stage 6 cm from the anal verge, SP was performed in 14 of the 15 (93%) patients with a CR and 32 of 33 (97%) of patients with residual disease (p < 0.00004). CONCLUSIONS: Significant tumor downstaging results from preoperative chemoradiation allowing sphincter sparing surgery in over 40% of patients whose tumors were located < 6 cm from the anal verge and who otherwise would have required colostomy.

Primary non-Hodgkin lymphoma of the small bowel.

PURPOSE: To clarify the natural history of primary lymphoma of the small bowel and identify preferred treatments for it. MATERIALS AND METHODS: A retrospective analysis of 61 patients with primary lymphoma of the small bowel was performed. The Ann Arbor stages were I in 20 patients, II in 28, and IV in 13. After resection or biopsy, 15 patients were treated with radiation therapy, 26 with chemotherapy, and 16 with combined-modality therapy. Four patients underwent no adjuvant treatment after resection. RESULTS: The actuarial 10-year overall survival and relapse-free survival for the patients with intermediate- and high-grade lymphoma were 47% and 53%, respectively. For the patients with low-grade lymphoma, these rates were 81% and 62%. For patients who underwent radiation therapy, combined-modality therapy, or chemotherapy, the recurrence rates inside the abdomen or pelvis were one of 12, two of 15, and five of 20, respectively, and those outside the abdomen or pelvis were four of 12, one of 15, and zero of 20, respectively. Four of the five abdominopelvic recurrences of disease in the chemotherapy group were among the nine patients who had Ann Arbor stage II disease. CONCLUSION: Chemotherapy lowered the recurrence rate outside the abdomen or pelvis. Patients with stage II disease may benefit most from radiation therapy.

Locally advanced rectal cancer: surgical complications after infusional chemotherapy and radiation therapy.

PURPOSE: To compare the surgical complication rate after further experience with infusional chemotherapy and radiation therapy for locally advanced rectal cancer. MATERIALS AND METHODS: Preoperative radiation therapy (45 Gy in 25 fractions over 5 weeks) and concurrent continuous infusion of 5-fluorouracil (300 mg.m-2.d-1) were given to 117 patients with rectal cancer. Approximately 6 weeks after therapy, surgery was performed. RESULTS: The histopathologic cancer stages were Tis-2N0 in 30 patients (26%), T2N1 in six (5%), T3N0 in 24 (21%), T3N1 in 18 (15%), T4N0 in six (5%), and T4N1 in one (1%); a complete response to preoperative therapy was histopathologically confirmed in 32 patients. A decrease in cancer stage allowed a sphincter-saving procedure in 68 patients (58%) and abdominoperineal resection in 49 patients (42%). Only one patient developed fistula; nine patients, perioperative wound complications; and four patients, pelvic infection. In the authors' previously reported chemotherapy and radiation therapy results (same protocol), eight (22%) of 37 patients developed fistulas and five (14%) developed pelvic abscess; in the authors' previous experience with preoperative radiation therapy only (median total dose, 45 Gy; dose range, 40.0-59.4 Gy), results were similar. CONCLUSION: Surgical complications after chemotherapy and radiation therapy are statistically significantly (P < .05) reduced with further experience.

Primary non-Hodgkin lymphoma of the large bowel.

PURPOSE: To characterize the natural history of primary non-Hodgkin lymphoma of the large bowel and identify prognostic factors. MATERIALS AND METHODS: Twenty-three patients with primary non-Hodgkin lymphoma according to strict criteria were identified. Seventeen patients underwent resection, and six patients underwent biopsy. Among 19 patients with intermediate- or high-grade lymphoma, 13 had diffuse large cell lymphoma. Ann Arbor stage was I in 15 cases, II in seven cases, and IV in one case. In 15 patients, the International Prognostic Index was available: 0, eight patients; 1, six patients; and 3, one patient. Postoperatively, six patients received combined chemotherapy and radiation therapy, eight patients received chemotherapy, and six patients received radiation therapy. Overall and relapse-free survival were calculated actuarially, and univariate analysis was performed with regard to stage, treatment, extent of surgery, and the International Prognostic Index. RESULTS: Median follow-up was 144 months. Two patients' disease recurred. Overall and relapse-free survival at 10 years were 61% and 82%, respectively. The International Prognostic Index was the only significant prognostic factor for overall survival (P = .03, log-rank test). CONCLUSION: The prognosis of primary non-Hodgkin lymphoma appears to be as good as that of low- or intermediate-grade lymphoma. The only significant prognostic factor for overall survival is the International Prognostic Index.

Impact of extensive intraductal component on recurrence and survival in patients with stage I or II breast cancer treated with breast conservation therapy.

BACKGROUND: The relationship between an extensive intraductal component (EIC) and recurrence and survival in patients with stage I or II breast cancer treated with breast conservation therapy has not been clearly defined. METHODS: 133 patients with stage I or II breast cancer who underwent breast conservation therapy between 1978 and 1990 at The University of Texas M. D. Anderson Cancer Center were retrospectively studied. All pathology slides were reviewed to determine tumor size, nuclear grade, extent of intraductal component, number of positive lymph nodes, and histologic margins. EIC was defined as ductal carcinoma in situ (DCIS) occupying 25% or more of the area encompassed by the infiltrating tumor and DCIS present in grossly normal adjacent breast tissue. RESULTS: 110 patients are alive, and 23 have died, with a median follow-up of 7 years; 85 of 133 patients had an intraductal component, but only 18 had an EIC. Locoregional control and disease-free and overall survival were not adversely affected by the presence of an EIC. Five of 133 patients had a locoregional recurrence, but only one had an EIC. CONCLUSIONS: EIC, if negative margins can be achieved, does not adversely affect disease-free or overall survival or local control rates.

Endobronchial brachytherapy with high-dose-rate remote afterloading for recurrent endobronchial lesions.

PURPOSE: To evaluate toxicity and efficacy of endobronchial brachytherapy with high-dose-rate (HDR) after-loading of iridium-192 for recurrent endobronchial lesions. MATERIALS AND METHODS: From 1988 to 1993, 81 patients with lung cancer previously treated with external beam radiation therapy were treated with palliative HDR endobronchial brachytherapy for symptoms due to relapse or persistent tumor of endobronchial bronchogenic origin. For most patients, Ir-192 was delivered in a dose of 3,000 cGy at 6 mm in two fractions over 2 weeks. RESULTS: Sixty-eight patients (84%) achieved some response: Twenty-six (32%) had excellent, 25 (31%) had moderate, and 17 (21%) had minimal symptomatic improvement with HDR endobronchial brachytherapy. Eleven patients had no change, and two became worse. The median duration of responses was 4.5 months. Those patients with an excellent response had a significantly better survival (13.3 months) compared with that of the other patients (5.4 months) (P = .01). There were two fatal complications, which were due to fistula and tracheal malacia. CONCLUSION: HDR endobronchial brachytherapy is an effective method to relieve airway obstruction promptly for patients with recurrent endobronchial lesions and may be considered as a boost for obstructive lesions before chemotherapy and external beam radiation therapy.

Apoptosis and mitosis as prognostic factors in pathologically staged N1 nonsmall cell lung cancer.

PURPOSE: This study aimed to established whether spontaneous apoptosis or mitosis has prognostic value among patients with pathologically staged N1 nonsmall cell lung carcinoma (NSCLC) treated with surgical resection with or without adjuvant therapy. METHODS AND MATERIALS: Material from 173 patients who had resections between 1970 and 1988 was analyzed for apoptosis and mitosis. There were 128 men and 45 women, with a median age of 61 years. There were 86 squamous cell carcinomas (SQ), 73 adenocarcinomas (AC), 3 large-cell carcinomas (LC), 6 SQ-AC, and 5 unclassified. Patients were observed from 2 to 209 months (median 27). Actuarial methods were used to assess survival and freedom from distant metastasis. RESULTS: In NSCLC, apoptosis was found to range from 0.2% to 2.8% (median 1.0%) and mitosis from 0 to 1.8% (median 0.4%). Tumors having higher levels of apoptosis also had higher levels of mitosis (p = 0.001). The values of neither apoptosis nor mitosis depended on size, location, differentiation of tumors, age, performance status, or weight loss of patients. However, the values of apoptosis depended on tumor histology in that high values (greater than or equal to the median) were more frequent in SQ (49%) than in AC/LC (29%) (p = 0.01). The overall survival for NSCLC patients, which was 33% at 5 years, did not depend on the level of either apoptosis or mitosis. The 5-year survival of patients having SQ was higher (43%) than that of patients having AC/LC (21%) (p = 0.03). Patients with high apoptosis showed significantly better 5-year overall (p = 0.008) and DMF (p = 0.0012) survivals in the SQ group compared to the AC/LC group. High mitosis compared to low mitosis was a significantly better predictor for 5-year survival (62% vs. 29%, respectively) (p = 0.035) in the SQ. However, high mitosis was a significantly worse 5-year DMF survival predictor compared to low mitosis: 13% vs. 56%, respectively (p = 0.05) in AC/LC. In the multivariate models for AC/LC, mitosis remained a significant predictor of 5-year distant metastasis (p = 0.025) controlling for treatment groups (p = 0.042), whereas apoptosis was an independently significant predictor of 5-year distant metastasis (p = 0.010). CONCLUSION: Squamous cell histology predicted significantly better 5-year overall and DMF survivals compared to AC/LC. Apoptosis was correlated with mitosis. Although apoptosis or mitosis did not predict survival or DM, high apoptosis or mitosis predicted significantly better survival in SQ and significantly worse survival in AC/LC with regard to overall and DMF survivals. In the multivariate models for AC/LC, apoptosis alone or mitosis with variable treatment was a significant predictor of 5-year distant metastasis. Thus, pretreatment levels of apoptosis or mitosis might be useful for predicting treatment outcome of SQ and AC/LC subsets of NSCLC when analyzed separately and for predicting metastatic incidence of AC/LC.

Limited-stage small-cell lung cancer: patient survival after combined chemotherapy and radiation therapy with and without treatment protocols.

PURPOSE: To compare survival of patients who undergo treatment in protocols versus survival of patients not in protocols. MATERIALS AND METHODS: Records of 81 adult patients with small-cell lung cancer who underwent chemotherapy and radiation therapy in 1987-1992 were reviewed retrospectively. Forty-one patients were in a protocol; 40 patients were not. Patient demographics and prognostic factors were not statistically significantly different. RESULTS: Median overall survival was 16.7 months in the nonprotocol group versus 29.0 months in the protocol group (P = .0023). Median disease-specific survival was 18.3 months in the nonprotocol group versus 27.1 months in the protocol group (P = .0176). Survival was not statistically significantly influenced by Karnofsky performance status, weight loss, or thoracic radiation dose. CONCLUSION: There was a highly statistically significant difference in survival outcome in the nonprotocol group versus the protocol group (P = .0023). Differences in chemotherapy-radiation therapy timing and other treatment-related factors may have contributed substantially to the improved survival in the protocol group.

ASTRO Research Fellowship: apoptosis as a predictor of tumor response to radiation in stage IB cervical carcinoma. American Society for Therapeutic Radiology and Oncology.

PURPOSE: Levels of apoptosis predict for tumor responsiveness to radiation in various animal systems. To investigate the potential role of apoptosis as a predictor of response in human tumors, a retrospective review was undertaken of patients with adenocarcinoma of the cervix whose primary lesion at presentation measured at least 4 cm and who underwent definitive radiation therapy. A previous report had indicated that roughly half this group of patients should have a long-term relapse free survival. METHODS AND MATERIALS: Pretreatment biopsy specimens of 44 patients with Stage IB adenocarcinoma of the cervix, whose primary lesion at presentation measured at least 4 cm in greatest dimension, were scored for apoptosis by two independent investigators without knowledge of the treatment outcome, and the results were averaged. Actuarial methods were used to assess overall survival, disease-free survival, determinate survival, and local control as a function of the baseline level of apoptosis. Patients ranged in age from 21 to 87 years and were treated with definitive radiotherapy between 1964 and 1989. Follow-up for the surviving patients ranged from 1 to 278 months, with a mean of 101 months. RESULTS: Patients whose tumors had a baseline level of apoptosis above the median value (2%) had a better overall survival than those with lower levels of apoptosis (p = 0.056). A similar trend for disease-free survival (p = 0.32) and determinate survival (p = 0.27) did not reach statistical significance, perhaps because of the small number of patients. Because only 6 of the 44 patients (13%) had a local tumor failure, it was not possible to establish a correlation between the pretreatment level of apoptosis and the local tumor control by radiation. CONCLUSION: The baseline level of apoptosis predicted for survival in patients with Stage IB cervical adenocarcinoma. Further investigation of the measurement of apoptosis as a potential predictive assay is warranted in other human tumor systems.

Significance of tumor size and radiation dose to local control in stage I-III diffuse large cell lymphoma treated with CHOP-Bleo and radiation.

PURPOSE: The purpose of this study was to evaluate the possible effect of adjunctive involved field (IF) radiotherapy on long-term local control for patients with Ann Arbor Stage I-III diffuse large cell lymphoma (DLCL) who achieved a complete remission on a combined modality program which included cyclophosphamide, doxorubicin, vincristine, prednisone, and Bleomycin (CHOP-Bleo). METHODS AND MATERIALS: One hundred and ninety patients with Ann Arbor Stage I-III DLCL were treated with CHOP-Bleo and radiotherapy. Analyses were undertaken to determine (a) response to treatment according to stage, extent of maximum local disease, and irradiation dose either < 40 Gy or > or = 40 Gy and (b) relapse patterns. RESULTS: A complete remission (CR) was achieved in 162 patients. Among patients who achieved a CR, local control was better for those who received tumor doses of > or = 40 Gy (97%) than for those who received < 40 Gy (83%) (p = 0.002.) Among those with extensive local disease, the corresponding control rates were 88% and 71%, respectively. A study of distant relapse patterns following a CR showed that the first relapse usually involved an extranodal site. CONCLUSION: Radiotherapy was an effective adjunctive treatment to CHOP-Bleo for patients with stage I-III DLCL who achieved a CR. Patterns of relapse suggested that total nodal irradiation (TNI) possibly could have benefited a small subset of patients.

Intermediate-grade lymphomas treated with cyclophosphamide-doxorubicin- vincristine-prednisone-bleomycin alternated with cyclophosphamide-methotrexate-etoposide-dexamethasone. Application of prognostic models to data analysis.

BACKGROUND: Numerous treatment strategies have been tried with the aim of improving results for patients with intermediate-grade lymphomas (IGL) over those achieved with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo), and numerous prognostic models have been developed to identify and separate risk groups. This study reports on a new protocol for Ann Arbor Stages II-IV IGL that consists of CHOP-Bleo alternated with a new regimen of cyclophosphamide, methotrexate, etoposide, and dexamethasone (CMED) and radiation therapy and demonstrates the usefulness of prognostic models for identifying risk groups and comparing treatment programs. METHODS: One hundred seventy patients with Ann Arbor Stages II-IV IGL were treated with alternating cycles of CHOP-Bleo and CMED for a total of 12 cycles. Involved field radiation therapy was interspersed with courses of chemotherapy for patients with Stage II and Stage III disease. Results were analyzed and compared with those of the authors' previous study of CHOP-Bleo and radiation therapy using the Ann Arbor staging system, their earlier prognostic model, and the recently published International Index. RESULTS: A complete remission occurred in 78% of the patients. The overall 5-year survival rate was 67%. Survival was better for patients with Ann Arbor Stage II disease (80%) than for those with Stage III or Stage IV (67% and 58%, respectively). High tumor burden, above-normal levels of serum lactic dehydrogenase, serum beta 2-microglobulin, and Ann Arbor Stage IV disease were adverse factors. The International Index and the authors' earlier prognostic model separated four prognostic groups. CHOP-Bleo/CMED was generally well tolerated. Neutropenic fever was the major complication that occurred in 25 patients during treatment. Six of these patients died of sepsis. CONCLUSIONS: This study demonstrated that CHOP-Bleo/CMED is a well-tolerated regimen that produced better results than those reported for a former study that used CHOP-Bleo alone. Further, results for CHOP-Bleo/CMED compared favorably with those of other second- and third-generation regimens. The study also validated the usefulness of prognostic models and, in particular, the new International Index for identifying risk groups.

Hodgkin's disease with a mediastinal mass greater than 10 cm: results of four different treatment approaches.

BACKGROUND: Management of Hodgkin's disease (HD) and large mediastinal adenopathy (LMA) usually includes intensive chemotherapy (CT) with or without radiation therapy (XT) regardless of stage. PATIENTS AND METHODS: One hundred and eighteen evaluable patients received one of four treatment regimens: (1) 6 cycles of MOPP or similar CT and XT; (2) 2 of MOPP followed by XT; (3) 6 of CVPP/ABDIC (cyclophosphamide, vincristine, procarbazine, prednisone/doxorubicin, bleomycin, decarbazine, prednisone, lomustine) followed by XT; or (4) 3 of NOVP (mitoxantrone, vincristine, vinblastine, procarbazine) and XT. XT doses included 30-40 Gy to areas of nodal involvement noted prior to therapy. RESULTS: Complete remission (CR) rates for groups 1, 2, 3, and 4 were 100%, 85%, 87%, and 96%. Respective 3-year freedom from progression (FFP) results were 88%, 66%, 82%, and 88%, and 3-year freedom from tumor mortality (FTM) results were 100%, 84%, 84%, and 100%. The presence of B symptoms and stage IV disease was correlated with lower CR and 3-year FFP rates but similar 3-year survival. CONCLUSIONS: Results of this study suggest that patients with stage I-III Hodgkin's disease and LMA greater than 10 cm treated with 3 NOVP and XT have results similar to those obtained for a similar group of patients treated with 2 to 6 MOPP or 6 CVPP/ABDIC and XT. NOVP has also been reported to produce limited toxicity in this trial and should be considered as an alternative to MOPP or doxorubicin-containing regimens in treatment of patients with early-staged disease and LMA greater than 10 cm.

Lymphography for staging lymphomas: is it still a useful procedure?

OBJECTIVE: The purpose of this study was to determine the current value of lymphography in a series of previously untreated patients with Hodgkin's and non-Hodgkin's lymphoma seen at the M. D. Anderson Cancer Center over a 1-year period. MATERIALS AND METHODS: From September 1989 through August 1990, 313 previously untreated patients with lymphoma were seen at our institution. In 221 of these, lymphography and CT were performed for abdominal staging. These studies were reviewed to determine if the examinations were complementary, or if the results of one or the other changed the staging in a significant number of patients. Staging was based on clinical findings, as laparotomies are rarely performed at this time. RESULTS: Lymphograms were abnormal and CT scans were normal in two patients with Hodgkin's disease and in two with non-Hodgkin's lymphomas. Biopsy proof of nodal disease was not available for any of these, but the nodes did not change after therapy in three patients. The other patient was seropositive for HIV, and HIV disease itself can cause nodal abnormalities. In one patient with Hodgkin's disease and 12 with non-Hodgkin's lymphoma, lymphograms were normal and CT scans were abnormal, showing enlarged nodes and/or abnormal architecture. CT scans obtained after therapy showed regression of nodal and extranodal masses. CONCLUSION: It was concluded that lymphographic findings did not significantly contribute to staging in these patients. This departure from previous experience may be due to improved state-of-the-art CT. In addition, the use of a combination of chemotherapy and radiation therapy to treat the lymphomas has increased, diminishing the need for detection of subtle nodal changes.