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Superior sulcus tumors represent a unique subset of nonsmall cell lung malignancies that have been described as early as 1838.1 Over the past several decades, the treatment of superior sulcus tumors has evolved to become multimodal. In a highly cited trial by the Southwest Oncology Group (SWOG), patients with T3-T4N0-N1 superior sulcus tumors were treated with preoperative cisplatin and etoposide and concurrent radiation to 45 grays (Gy), followed by thoracotomy for disease that was stable or responsive to this treatment. Five-year survival rates were promising at 44% for the entire group and >50% for cases in which a complete response was achieved.2,3 As a result, many have advocated preoperative chemoradiation, even for resectable superior sulcus tumors. However, no studies have established that preoperative chemotherapy, with or without radiation treatment, is superior to surgical resection followed by postoperative treatment in cases that are resectable at diagnosis. In this context, we initiated a prospective phase 2 study of patients with resectable superior sulcus tumors treated with surgical resection followed by adjuvant chemoradiation. Radiation was delivered in twice-daily fractions to minimize long-term toxicity, which is particularly important as these tumors are often close to the brachial plexus, and to minimize tumor-cell repair and repopulation between fractions.4 We report here the long-term results of this study, focusing on survival outcomes, failure patterns, and treatment complications, with the goal of establishing if this treatment approach is safe and effective for this relatively rare but aggressive disease.

BACKGROUND We sought here to improve the toxicity of conventional concurrent chemoradiation therapy for stage III non-small cell lung cancer (NSCLC) by using proton-beam therapy to escalate the radiation dose to the tumor. We report early results of a phase II study of high-dose proton therapy and concurrent chemotherapy in terms of toxicity, failure patterns, and survival.

BACKGROUND: Lung cancer is the leading cause of cancer death for both men and women, but the disease course differs between the sexes. To the authors' knowledge, sex-based differences in outcomes among the population of nonsmall cell lung cancer (NSCLC) patients receiving radiation have not been well defined. METHODS: Data for 831 patients (319 women and 512 men) with stage I to III NSCLC and treated with ≥45 Gray of radiation between March 1985 and November 2003 were retrospectively analyzed (grading determined according to the 1997 American Joint Committee on Cancer grading system). RESULTS: Women were more likely to have earlier stage disease, to have smoked

BACKGROUND The current study was performed to assess the value of 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in predicting the pathologic response and survival of patients with esophageal carcinoma treated with preoperative chemoradiation (CRT) and tumor resection. Preliminary reports suggest that FDG-PET may be predictive of the response of esophageal carcinoma patients to preoperative CRT. METHODS Eighty-three patients with resectable esophageal carcinoma who underwent preoperative CRT and FDG-PET and tumor resection were evaluated for pathologic response to CRT, percent residual tumor, and survival. RESULTS The majority of patients in the current study were men (74 of 83 patients; 89%). Most tumors were adenocarcinomas (73 of 83 tumors; 88%) and clinical EUST3/4 (69 tumors; 83%) or N1 (46 tumors; 55%). FDG-PET after preoperative CRT identified pathologic responders but failed to rule out microscopic residual tumor in 13 of 73 cases (18%). Pathologic response was found to correlate with the post-CRT FDG-PET standardized uptake value (SUV) (P = 0.03) and a post-CRT FDG-PET SUV of ≥ 4 was found to be the only preoperative factor to correlate with decreased survival (2-year survival rate of 33% vs. 60%; P = 0.01). On univariate Cox regression analysis, only post-CRT FDG-PET was found to be correlated with post-CRT survival (P = 0.04). CONCLUSIONS Post-CRT FDG-PET was found to be predictive of pathologic response and survival in patients with esophageal carcinoma who undergo preoperative CRT. Esophagectomy should still be considered even if the post-CRT FDG-PET scan is normal because microscopic residual disease cannot be ruled out. Cancer 2004. © 2004 American Cancer Society.

BACKGROUND We present the results of doxorubicin-based chemotherapy with or without involved-field radiotherapy for patients with diffuse large B-cell lymphoma (DLBCL) according to the international prognostic index (IPI). METHODS From September 1988 through December 1996, 294 patients with Stage I–IV Working Formulation large B-cell or T-cell lymphomas were treated prospectively on two protocols at our center. Diagnoses were reclassified subsequently according to the new World Health Organization classification. Two-hundred and twenty-four patients had DLBCL, including 24 patients with primary mediastinal large B-cell lymphoma. Treatment consisted of a median of six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy with or without involved-field radiotherapy (median dose, 39.6 Gy). RESULTS/CONCLUSIONS. The median length of follow-up among surviving patients was 5.0 years. Patient subgroups differed from each other in terms of progression-free (P = 0.003), cause-specific (P = 0.003), and overall (P = 0.001) survival rates when analyzed by IPI. Five-year progression-free, cause-specific, and overall survival rates for 212 patients with an IPI of 0–2 were 73%, 84%, and 82%, respectively, versus only 37%, 33%, and 32% for 12 patients with an IPI of 3–4. To improve our results, we are conducting clinical trials with young DLBCL patients and with patients who are older than 60 years. The young DLBCL patients, who have more than two adverse prognostic features, are receiving high-dose chemotherapy and autologous stem cell rescue. The patients who are older than 60 years, regardless of IPI, are receiving rituximab immunotherapy and liposomal CHOP chemotherapy with or without involved-field radiotherapy. Cancer 2002;94:3083–8. © 2002 American Cancer Society. DOI 10.1002/cncr.10583

BACKGROUND Mediastinal recurrence remains the most common cause of failure in patients with mediastinal T-cell lymphoblastic lymphoma (LBL). The role of mediastinal radiation therapy in improving local disease control and overall prognosis is not well-known with modern intensive chemotherapy. The objective of this study was to investigate the role of mediastinal radiation therapy in patients who achieve a complete response (CR) to chemotherapy. METHODS The authors reviewed 47 patients with mediastinal T-cell LBL with or without bone marrow (BM) involvement who presented between 1980 and 1998. The median patient age was 25 years, and 33 patients (70%) were males. BM involvement was present in 16 patients (34%), 5 patients (11%) were in leukemic phase, lymph node involvement in was present 23 patients (49%), hepatosplenomegaly was present in 4 patients (9%), and pleural effusions were present in 22 patients (45%). The initial chemotherapy regimens were fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) in 23 patients; cyclophosphamide, vincristine, doxorubicin, and dexamethasone in 9 patients; vincristine, doxorubicin, and dexamethasone in 4 patients; cyclophosphamide, doxorubicin, vincristine, and prednisone in 4 patients; and other in 7 patients. Forty-three patients achieved a CR to chemotherapy and were the subject of this analysis. Nineteen of those patients received adjuvant mediastinal radiation therapy at a dose ranging from 26 grays (Gy) to 39 Gy. RESULTS There was no difference in patient characteristics between the 19 patients who were treated with mediastinal radiation therapy and the 24 patients who did not receive mediastinal radiation therapy. The median follow-up for all 43 patients was 43 months. The 5-year overall survival (OS) rate was 66%, and the freedom from progression (FFP) rate was 64%. None of 19 patients who received radiation therapy experienced a mediastinal recurrence compared with 8 of 24 patients who did not receive radiation therapy and experienced a mediastinal recurrence. Patients who were treated with mediastinal radiation therapy had a significantly better mediastinal FFP rate (P = 0.01), but the differences in overall FFP and OS rates were not significant (P = 0.14 and P = 0.25, respectively). The effectiveness of the hyper-CVAD regimen seemed to underscore the role of mediastinal radiation therapy; only 2 patients experienced a recurrence among 16 patients who received mediastinal radiation therapy, both outside the mediastinum. This compared with two patients who experienced a recurrence among six patients who did not receive mediastinal radiation therapy, both in the mediastinum. CONCLUSIONS Local radiation therapy significantly decreased the risk of mediastinal recurrence in adult patients with mediastinal T-cell lymphoblastic lymphoma. The benefit of adjuvant radiation therapy was particularly evident in patients treated with more intensive chemotherapy regimens. Cancer 2002;94:2738–44. © 2002 American Cancer Society. DOI 10.1002/cncr.10552

BACKGROUND Lymphocyte-predominant Hodgkin disease (LPHD) is rare and has a natural history different from that of classic Hodgkin disease. There is little information in the literature regarding the role of chemotherapy in patients with early-stage LPHD. The objective of this study was to examine recurrence free survival (RFS), overall survival (OS), and patterns of first recurrence in patients with LPHD who were treated with radiotherapy alone or with chemotherapy followed by radiotherapy. METHODS From 1963 to 1996, 48 consecutive patients ages 16–49 years (median, 28 years) with Ann Arbor Stage I (n = 30 patients) or Stage II (n = 18 patients), very favorable (VF; n = 5 patients) or favorable (F; n = 43 patients) LPHD, according to the European Organization for Research and Treatment of Cancer and Groupe d'Etude des Lymphomes de l'Adulte (EORTC-GELA) criteria, received radiotherapy alone (n = 37 patients) or received chemotherapy followed by radiotherapy (n = 11 patients). The percentages of patients with VF disease (11% vs. 9% in the radiotherapy group vs. the chemotherapy plus radiotherapy group, respectively) or F disease (89% vs. 91%, respectively) within the two treatment groups were similar (P = 1.00). A median of three cycles of chemotherapy with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or with mitoxantrone, vincristine, vinblastine, and prednisone (NOVP) was given initially to six patients and five patients, respectively. A median total radiotherapy dose of 40 grays (Gy) given in daily fractions of 2.0 Gy was delivered to both treatment groups. RESULTS The median follow-up was 9.3 years, and 98% of patients were observed for ≥ 3.0 years. RFS was similar for patients who were treated with radiotherapy alone and patients who were treated with chemotherapy followed by radiotherapy (10-year survival rates: 77% and 68%, respectively; P = 0.89). The OS rate also was similar for the two groups (10-year survival rates: 90% and 100%, respectively; P = 0.43). MOPP or NOVP chemotherapy did not reduce the risk of recurrence outside of the radiotherapy fields. CONCLUSIONS MOPP or NOVP chemotherapy did not improve RFS or OS significantly in patients with VF or F LPHD, although the statistical power was limited. Ongoing clinical trials will help to clarify the role of a watch-and-wait strategy or systemic therapy, including anthracycline (epirubicin or doxorubicin), bleomycin, and vinblastine-based chemotherapy or antibody-based approaches, in the treatment of these patients. Cancer 2002;94:1731–8. © 2002 American Cancer Society. DOI 10.1002/cncr.10404

BACKGROUND Prognostic factors for solitary plasmacytoma of bone (SPB), whether measured before or after radiotherapy (RT), have not been established. The authors analyzed multiple factors for myeloma-free survival (MFS) and cause-specific survival (CSS) in SPB patients treated with RT alone. METHODS Between 1965 and 2000, 60 patients with carefully staged SPB were treated with RT alone at the M. D. Anderson Cancer Center. Patient ages ranged from 29–77 years (median, 54 years), and 75% of patients had a myeloma (M) protein in the blood and/or urine. No patients showed other lesions on skeletal survey or, in recent years, magnetic resonance imaging (MRI) of the spine; marrow aspirate was normal in all patients. Radiotherapy to the solitary lesion was given to a total dose of 30–70 Gy (median, 46 Gy). The authors analyzed the impact of multiple factors on MFS and CSS, including resolution v. persistence of M protein after RT, secretory v. nonsecretory disease at diagnosis, presence v. absence of an associated soft tissue mass on computed tomography or MRI scan, magnitude of serum M protein elevation at diagnosis, age, spinal v. nonspinal location, Karnofsky performance status, total RT dose, and tumor size. RESULTS Median follow-up was 7.8 years (range, 1.0–25.5 years). On multivariate analysis, persistence of M protein more than one year after RT was the only independent adverse prognostic factor for MFS (P = 0.005) and CSS (P = 0.04). Most patients with M protein that persisted for more than one year after RT were diagnosed with multiple myeloma within 2.2 years of treatment. CONCLUSIONS Patients with M protein that persists for more than one year after RT should be monitored frequently and considered for standard chemotherapy followed by intensive consolidation therapy when they either develop symptoms or show an increasing M protein level. Cancer 2002;94:1532–7. © 2002 American Cancer Society. DOI 10.1002/cncr.10366

BACKGROUND In the current study, the authors analyzed prognostic factors in patients with aggressive lymphoma treated with a chemotherapy regimen comprised of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without radiotherapy. METHODS Between September 1988 and December 1996, 294 patients with newly diagnosed, clinical Ann Arbor Stage I-IV, aggressive lymphoma were enrolled on 2 protocols at The University of Texas M. D. Anderson Cancer Center. Patients on these studies had a relatively favorable prognosis; 100% had M. D. Anderson tumor scores ≤ 2 and 95%% had International Prognostic Indices (IPIs) ≤ 2. Treatment was comprised of 5 ± 1 (mean ± the standard deviation) cycles of CHOP chemotherapy with or without involved-field radiotherapy to a total dose of 40.1 ± 3.3 grays (mean ± the standard deviation). RESULTS The median length of follow-up was 61 months. Three factors were found to retain independent prognostic significance on multivariate analysis in terms of progression-free survival: > 1 extranodal site of disease (P 60 years (P = 0.001), bulky disease (P = 0.016), and an at least 10% elevation in the serum LDH level (P = 0.040) also were found to be independent prognostic factors for overall survival. CONCLUSIONS The independent prognostic factors in the current study suggest that either the M. D. Anderson tumor score system or the IPI can be used to select which aggressive lymphoma patients are at high risk for disease recurrence based on their having more than two adverse factors and who consequently are candidates for more intensive frontline therapy. Involved-field radiotherapy should be considered in those patients with bulky lymphomas. Cancer 2001;91:2440–60. © 2001 American Cancer Society.

BACKGROUND The current study was undertaken to define the natural history and patterns of failure of localized non-Hodgkin lymphoma (NHL) involving the thyroid gland. METHODS A retrospective review of 51 patients with Ann Arbor Stage I or II NHL involving the thyroid gland was performed. The median age of the patients was 59 years. There were 33 females. There were 21 patients with Stage I disease and 30 patients with Stage II disease. The International Prognostic Index (IPI) was known for 43 patients (it was 0 in 16 patients and ≥ 1 in 27 patients). Fifteen patients had mediastinal involvement. Four patients underwent thyroidectomy, 18 patients received radiation therapy, 5 patients received chemotherapy, and 24 patients received combined modality therapy (CMT) with chemotherapy and radiation therapy. Treatment modality, patient gender, IPI, disease stage, and mediastinal involvement were examined for significance with regard to overall survival (OS) and failure free survival (FFS). RESULTS The 5-year OS and FFS rates were 64% and 76%, respectively. The 5-year FFS rates by treatment regimen were 76% for radiation therapy, 50% for chemotherapy, and 91% for CMT (P = 0.15). IPI was found to be the only significant predictor of OS. The 5-year OS rates were 86% and 50%, respectively, for IPIs of 0 and ≥ 1 (P = 0.02). None of the 5 variables were found to correlate significantly with FFS, although the 5-year FFS rates were 93% and 68%, respectively, for IPIs of 0 and ≥ 1 (P = 0.08). Eleven patients failed treatment. Nine patients had a component of distant failure across the diaphragm. CONCLUSIONS The prognosis of patients with localized NHL involving the thyroid gland appears to be very good, especially when CMT is used. Distant recurrences appear to account for the majority of treatment failures. The IPI was found to be a significant prognostic factor for OS and a marginal one for FFS. Cancer 2001;91:629–35. © 2001 American Cancer Society.

BACKGROUND Total body irradiation (TBI) is commonly used with autologous bone marrow transplantation (BMT) for treatment of hematologic malignancies. Pulmonary complications of TBI can cause long-term morbidity and mortality. The authors have compared the pulmonary toxicity and efficacy of two different TBI fractionation regimens in otherwise identical autologous BMT protocols. METHODS Between 1990 and 1997 patients younger than 60 years of age with low-grade lymphoma at high risk of treatment failure were enrolled on one of two sequential protocols for autologous BMT differing only in their TBI regimens. The preoperative chemotherapy regimens were identical and consisted of intravenous etoposide (1500 mg/m2) for 1 day, intravenous cyclophosphamide (60 mg/kg) for 2 days, and mesna (10 mg/kg). The TBI used in protocol A consisted of twice-daily fractions of 1.7 grays (Gy) for 3 days to a total of 10.2 Gy through lateral fields, with no lung shielding. In protocol B, the TBI consisted of 3 Gy once daily for 4 days to a total of 12 Gy through anteroposterior fields, with lung shielding (5 half-value layers) during the third dose. Fifty-eight patients were treated on protocol A and 24 on protocol B. The groups were equivalent with regard to age, performance status (PS) and gender. Lung function was assessed objectively by pulmonary function tests (PFTs) before and at intervals after TBI. The pulmonary function parameters assessed included forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), forced expiratory flow between 25% and 75% of vital capacity (FEF25–75), diffusing capacity for carbon monoxide (DLCO), and total lung capacity (TLC). Each patient's post-TBI PFTs were normalized to the corresponding pre-TBI values and analyzed using a random effects model. Clinical pulmonary function status was scored according to Radiation Therapy Oncology Group criteria for acute and late lung toxicity. All clinical pulmonary toxicities such as pneumonitis, pneumonia, and diffuse alveolar hemorrhage, whether specifically related to TBI or not, were scored. Toxicity was classified as either acute (i.e., occurring within 90 days of TBI) or late (i.e., occurring more than 90 days after TBI). The endpoints of analysis were overall survival (OS), freedom from progression, and chronic pulmonary toxicity. Survival, progression, and complication free survival were computed using the method of Kaplan and Meier. RESULTS Three-year actuarial OS rates were 66% and 67% for protocols A and B, respectively. Patients 50 years of age or older had a hazard ratio of death 3.5 times higher than younger patients. Freedom from progression was significantly different for the 2 TBI regimens (P < 0.001; log-rank test): 31% at 3 years in the protocol A group compared with 82% in protocol B group. Patients on protocol A had a rate of progression 4.7 times higher than patients on protocol B. The TBI protocols did not differ significantly in their effects on FVC, FEV1, FEF25–75, DLCO, and TLC. Patients 45 years of age or older had lower average posttransplant values of FEV1, FVC, and DLCO than younger patients. There was no significant difference in acute or late toxicity rates between patients on the two protocols. Seven of the 57 patients in the twice-daily TBI (protocol A) group had acute pulmonary events (Grade 3 or greater), compared with 6 of the 24 patients in the once-daily (protocol B) group (P = 0.19). The 3-year freedom from late complications rate was 80% in the protocol A group and 70% in the protocol B group (P = 0.45). Patients with a PS of 1 had a hazard ratio of late complications 3.2 times greater than patients with a PS of 0 (P < 0.001). CONCLUSIONS It is possible to intensify TBI from a total dose of 10.2 Gy delivered in 6 twice-daily fractions to 12 Gy delivered in 4 once-daily fractions without significantly increasing the risk of pulmonary toxicity. The increased dose may contribute to a decrease in the recurrence rate in these patients. Cancer 2001;92:1949–58. © 2001 American Cancer Society.

BACKGROUND Although surgery is considered standard therapy for unicentric Castleman disease, favorable responses to radiotherapy also have been documented. The authors undertook this study to analyze the clinical factors, treatment approaches, and outcomes of patients with unicentric or multicentric Castleman disease, and to report the outcomes of patients with unicentric Castleman disease treated with radiotherapy. METHODS The authors reviewed the medical records of 22 patients who had received a histologic diagnosis of Castleman disease at the University of Texas M. D. Anderson Cancer Center between 1988 and 1999. One patient with a concurrent histopathologic diagnosis of nonsecretory multiple myeloma was excluded from the study. In all patients, the diagnosis of Castleman disease was based on the results of lymph node biopsies. Disease was categorized as being either unicentric or multicentric and further subdivided into hyaline vascular, plasma cell, or mixed variant histologic types. Clinical variables and outcomes were analyzed according to treatment, which consisted of surgery, chemotherapy, or radiotherapy. RESULTS Records from 21 patients were analyzed: 12 had unicentric disease, and 9 had multicentric disease. The mean follow-up time for the entire series was 51 months (median, 40 months). Four patients with unicentric disease were treated with radiotherapy alone: 2 remain alive and symptom free, 2 died of causes unrelated to Castleman disease and had no evidence of disease at last follow-up. Eight patients with unicentric disease were treated with complete or partial surgical resection, and all are alive and asymptomatic. All nine patients with multicentric disease were treated with combination chemotherapy: five are alive with no evidence of disease, and four are alive with progressive disease. CONCLUSIONS Surgery results in excellent rates of cure in patients with unicentric Castleman disease; radiotherapy can also achieve clinical response and cure in selected patients. Multicentric Castleman disease is a more aggressive clinical entity and is most effectively treated with combination chemotherapy, whereas the role of radiotherapy in its treatment remains unclear. Cancer 2001;92:670–6. © 2001 American Cancer Society.

BACKGROUND The authors previously reported that central lymphatic irradiation (CLI) can induce molecular remission in patients with Stage I–III follicular lymphoma, as measured by polymerase chain reaction analysis for t(14;18) (q32;q21). Hematologic toxicity has been considered a major consequence of CLI. This study was undertaken to analyze the patterns of hematologic recovery after CLI. METHODS Thirty-three patients with Stage I–III follicular lymphoma were treated with CLI between January 1993 and February 1998. CLI consisted of irradiation to mantle, upper two-thirds of abdomen, and pelvic fields. Each field was treated to 30.0–30.6 grays (Gy) at 1.5–1.8 Gy per fraction, with a boost to 36.0–39.6 Gy at the same rate to the sites of macroscopic disease. A break of approximately 4 weeks was given after treatment of each field. Twenty-four patients who were followed for a minimum of 1 year from the end of CLI form the basis of this analysis. Fourteen patients were male. Three patients had Stage I disease, 6 patients had Stage II disease, and 15 patients had Stage III disease. The International Prognostic Index (IPI) for malignant lymphoma was 0 for 5 patients, 1 for 13 patients, and 2 for 6 patients. The Eastern Cooperative Oncology Group performance status was 0 for 21 patients and 1 for 3 patients. The median values for their pretreatment characteristics were as follows: age, 60 years (range, 34–73 years); height, 173 cm (range, 155–193 cm); weight, 79 kg (range, 57–107 kg); body surface area (BSA), 1.95 m2 (range, 1.61–2.31 m2); bone marrow cellularity, 27%(range, 2–75%), platelet count, 233,000/mm3 (range, 139,000–339,000/mm3), white blood cell (WBC) counts, 6400/mm3 (range, 4200–10,900/mm3); and hemoglobin, 14.5 mg/dL (range, 11.8 –16.6 mg/dL). The median duration of CLI was 159 days (range, 137–345 days). Ten patients had cardiovascular disease. The number of sites receiving a boost dose of ≥ 36.0 Gy was 0 sites in 1 patient, 1 site in 6 patients, 2 sites in 11 patients, 3 sites in 5 patients, and 4 sites in 1 patient. The platelet, hemoglobin, and WBC counts were followed every 3 months after completion of CLI. These counts were normalized to the pretreatment counts for statistical analyses. Univariate and multivariate analyses were performed to investigate the correlations between patient factors and hematologic status at 1 year posttreatment. Pearson correlation analysis was used for the continuous factors (patient age, height, weight, BSA, bone marrow cellularity, and duration of CLI), and the Mann–Whitney test was used for categoric factors (IPI, gender, performance status, stage, number of sites receiving ≥ 36.0 Gy, and presence or absence of cardiovascular disease). RESULTS There was continued recovery, essentially approaching the pretreatment levels, over 3 years for platelet, WBC, and hemoglobin counts. Factors that were associated significantly with normalized platelet counts at 1 year by univariate analyses were age (P = 0.015) and cardiovascular disease (P = 0.041). Age was the only significant factor by multivariate analyses, with older patients having lower platelet counts at 1 year posttreatment. No factors were found that were associated significantly with 1-year normalized WBC or hemoglobin levels by either univariate or multivariate analyses. CONCLUSIONS All three of the hematologic components (platelets, WBC, and hemoglobin) essentially recover after patients undergo CLI over a 3-year period. Older age was the only significant adverse factor that affected the platelet recovery, as detected by multivariate analysis. Cancer 2001;92:1074–9. © 2001 American Cancer Society.

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. Cancer 2000;89:1371–9. © 2000 American Cancer Society.

BACKGROUND Lymphoma of the nasal cavity and paranasal sinuses is a rare presentation of extranodal lymphoma with a natural history that is not well characterized in this era of combination chemotherapy. The goals of this retrospective study were 1) to define the natural history of sinonasal lymphomas; 2) to compare the results of radiation therapy (XRT) alone with those of combined modality therapy (CMT) in the treatment of patients with lymphoma of the nasal cavity and paranasal sinuses; and 3) to define prognostic factors for each treatment. METHODS Between 1947 and 1993, 70 patients with newly diagnosed lymphoma of the nasal cavity and paranasal sinuses were treated. The Ann Arbor stages were: Stage IE: 42 patients; Stage IIE: 14 patients; Stage IIIE: 2 patients; and Stage IV: 12 patients. The distribution of T classifications of the primary tumors was as follows: T1: 2 patients; T2: 16; T3: 18; and T4: 34. Greater than 90% of the patients had intermediate grade lymphoma (Working Formulation), and none had follicular lymphoma. Twenty-eight patients received XRT alone, and 42 received CMT. RESULTS The actuarial 5-year freedom from progression (FFP) and overall survival (OS) rates for the entire group were 57% and 52%, respectively. For patients with localized disease (Stages IE and IIE) receiving CMT, the actuarial 5-year FFP and OS were 83% and 67%, respectively. In multivariate analysis, treatment with CMT (P = 0.0005) and stage (IE vs. IIIE-IV) (P = 0.0001) were associated with improved FFP. In the group of patients receiving XRT, extent of disease (Stage IE, T1-3 vs. Stage IE, T4 vs. Stage IIE-IV) (P = 0.0001) was the only clinical characteristic associated with improved FFP in multivariate analysis. For patients receiving CMT, International Index (0 vs. 1-3 vs. 4, 5) (P = 0.0001) was the only significant factor predictive of improved FFP in multivariate analysis. One patient failed in the central nervous system (CNS) after initial therapy as a result of a radiation therapy marginal miss. CONCLUSIONS In a Western population, patients with localized lymphoma of the nasal cavity and paranasal sinuses have a favorable prognosis when treated with CMT. FFP is significantly improved by treatment with CMT. For patients treated with XRT, extent of disease is the strongest predictor of outcome. International Index is the most significant prognostic factor for patients receiving CMT. Failure in the CNS is rare after initial therapy and is associated with local failure. Cancer 1997; 80:477-88. © 1997 American Cancer Society.

BACKGROUND A survival difference between white and black females has been reported after diagnosis and treatment for breast carcinoma. Although multivariate analyses demonstrate that the survival difference is less or nonexistent when additional prognostic factors are considered, study results have been inconsistent. The objective of this study was to examine further the role of ethnicity as an independent prognostic factor for breast carcinoma survival among white and black females treated over a 30-year period. METHODS Among 3382 eligible white and black females who registered at M. D. Anderson Cancer Center (MDACC) from 1958 to 1987, ethnicity, age, socioeconomic status (SES), stage of disease, and treatment were examined. Data were obtained from the hospital tumor registry and survival was compared using actuarial life tables and multivariate Cox regression analyses. RESULTS Univariate analyses demonstrated that the survival difference between white and black females was significant, with black females having a 1.63 times higher risk of mortality at 5 years compared with white females (confidence interval (CI), 1.47-1.82), with ethnicity a significant predictor of survival (P < 0.001). After controlling for SES, stage, and treatment, the relative risk was 1.12 (CI, 1.00-1.25) and ethnicity was no longer a strong predictor of survival (P = 0.048). CONCLUSIONS In this hospital population, the white and black female survival difference, which was highly significant when only univariate analyses were considered, became marginally significant after controlling for other prognostic factors. Cancer 1996;78:1241-7.

Background. Follicular lymphoma is a clearly defined type of malignant lymphoma. The many treatment approaches reported in the literature attest to the lack of agreement on its best management. The treatment experiences of patients with Stage I or II follicular lymphoma who were at risk for at least 5 years were reviewed to assess their survival, disease free survival, and patterns of failure. Methods. Between 1974 and 1988, 144 patients with Stage I or II follicular lymphoma were treated at The University of Texas M. D. Anderson Cancer Center. Initial staging studies included lymphangiography in 87% of the patients, computerized tomography of the abdomen and pelvis in 60%, bone marrow biopsy in 98%, and diagnostic or staging laparotomy in 33%. Forty-five patients were treated with regional radiotherapy, 84 patients with combined chemotherapy and radiotherapy, and 15 patients were treated with chemotherapy alone. Results. With a median follow-up of 8.7 years (range, 48-182 months) the actuarial survival rates at 5, 10, and 15 years were 81, 69, and 63%, respectively. The freedom from relapse (FFR) rates were 66, 56, and 46%, respectively. The FFR rate was better for patients treated with chemotherapy-radiotherapy than for patients treated with radiotherapy alone (63 vs. 35% at 15 years). In addition, there were no relapses after 7.5 years in patients treated with chemotherapy-radiotherapy, but relapses continued even beyond 15 years in patients treated with radiotherapy alone. Univariate analysis for each of the treatment groups revealed age to be the only significant prognostic factor. There was no significant difference in survival or disease free survival rates for the three histologic subtypes of follicular lymphoma. Conclusion. The addition of chemotherapy to radiotherapy may have increased the probability of cure for patients with Stages I or II follicular lymphoma. Cancer 1995 ;75 :2361-7.

Background. Primary lymphomas of the uterus or cervix are so rare that treatment series of single institutions consist of very small numbers of patients, making standard treatment difficult to define. The outcome of patients treated with a combination of chemotherapy and radiation therapy was analyzed for all but patients with the most advanced disease. Methods. From 1976 to 1992, 16 patients received definitive treatment. Thirteen patients had intact uteri (group 1) and 3 presented with paracolpal lymphomas after previous hysterectomies (group 2). Twelve of the patients received chemotherapy and external irradiation. The remaining four underwent only chemotherapy. The overall survival and freedom from disease progression were analyzed according to Kaplan-Meier methods. Prognoses were related to the International Index, Ann Arbor stage, and International Federation of Gynecology and Obstetrics stage. Results. Five-year survival and freedom from disease progression were 77 and 67%, respectively, for group 1, and all patients in group 2 were cured. A statistically signinificant correlation of survival with scores of the International Index was found in group 1. For patients with scores in the low or low-intermediate range (n = 10), 5-year survival was 90%. All patients who scored in the high-intermediate or high range (n = 3) died by 66 months after their diagnosis (P = 0.0153). The Ann Arbor stage had less predictive value, with 5-year survival of 89% for Stage I and II patients (n = 9), compared with 50% survival for the four Stage III and IV patients (P = 0.0701). International Federation of Gynecology and Obstetrics staging did not predict outcome. Conclusions. The combination of chemotherapy and irradiation is the most effective treatment regimen for all uterine and cervical lymphomas. The International Index is most predictive of outcome. Cancer 1995 ;75 : 2392-9.

Background. The authors retrospectively analyzed 87 patients with malignant thymoma treated at M. D. Anderson Cancer Center between 1951 and 1990. The analysis examined the clinical stages, histologic types, and treatment modalities and attempted to determine if chemotherapy had an impact on survival. Methods. The patients were divided into three groups by their year of treatment and treatment modality. Patients treated between 1951 and 1975 were in Group I; patients treated between 1976 and 1980 were in Group II; and patients treated between 1981 and 1990 were in Group III. Most of the patients (18 [72%] in Group I; 16 [62%] in Group II; and 18 [50%] in Group III) had surgical resection alone or with radiotherapy. Patients with advanced-stage disease in Group I received single-agent chemotherapy, whereas patients with advanced-stage disease in Group II received a different, combination chemotherapy regimen, and those in Group III were treated primarily with cisplatin- and doxorubicin-based combination chemotherapy, e.g., the cyclophosphamide doxorubicin, and cisplatin with or without prednisone. The 17 patients treated with cisplatin with or without prednisone were separately evaluated for survival according to their response. Results. Twenty-eight patients (5 [20%] in Group I; 6 [23%] in Group II; and 17 [47%] in Group III) received chemotherapy alone or after surgery or radiotherapy. The cisplatin with or without prednisone regimen was used in 17 Group III patients for initial treatment or for relapse. The overall response rate among the patients receiving the cisplatin with or without prednisone regimen was 64%; 6 (35%) had a complete response, and 5 (29%) had a partial response. Thirty-one (36%) of the 87 total patients had 45 recurrent tumors; the lung (29%), pleura (22%), and mediastinum (18%) were the most common sites of recurrence, whereas bone was the most common distant metastatic site. The 5-year survival rate was 70% in patients with Stage I disease, 71% in patients with Stage II or III disease, and 46% in patients with Stage IV disease. The 10-year survival rate was 70% in patients with Stage I disease, 47% in patients with Stage II or III disease, and 21% in patients with Stage IV disease. Statistical analysis indicated a significant difference among the survival rates of patients with noninvasive Stage I, invasive Stage II plus III (P = 0.033), and Stage II plus III and IV tumors (P = 0.056), but not between patients with Stage II or III tumors. Patients with a major response to the cisplatin with or without prednisone regimen had a significant survival improvement compared to those with no response (P = 0.002, log-rank test). Conclusions. Because thymoma is a chemosensitive tumor and frequently recurs in patients with Stage II or greater disease, chemotherapy carries a potential survival benefit and should be incorporated into the multimodality approach to prolong disease-free survival.

The optimal treatment for locally advanced superior sulcus tumors is not clear. The authors report long-term results of a trial examining the safety and efficacy of surgery followed by concurrent chemoradiation therapy for this disease.Thirty-two patients with resectable or marginally resectable superior sulcus tumors at The University of Texas MD Anderson Cancer Center from 1994 to 2010 were enrolled in a prospective trial. Surgery involved segmentectomy or lobectomy with en bloc resection of the involved chest wall and complete nodal staging; radiation therapy (RT) began 14 to 42 days later to a dose of 60 grays (Gy) in 50 1.2-Gy fractions if surgical margins were negative or 64.8 Gy in 54 1.2-Gy fractions if margins were positive. Two cycles of etoposide (50 mg/m(2) ) and cisplatin (50 mg/m(2) ) were given during RT, and another 3 cycles were given after RT. Eleven patients underwent prophylactic cranial irradiation (PCI).The protocol completion rate was 78%. Gross total resection was accomplished in all 32 patients; 28% underwent R1 resection. Operative mortality was 0%. The most common surgical complication was postoperative pneumonia (25%). At a median follow-up time of 53.4 months (range, 2-154 months), the 2-year, 5-year, and 10-year rates of locoregional control were 84%, 76%, and 76%; distant metastasis-free survival, 52%, 48%, and 48%; disease-free survival, 49%, 45%, and 45%; and overall survival, 72%, 50%, and 45%, respectively. The brain was the most common site of distant failure (n = 5), but no patient who received PCI experienced brain metastasis.Surgery followed by postoperative chemoradiation is safe and effective for the treatment of marginally resectable superior sulcus tumors.

BACKGROUND: Prior studies have demonstrated that among patients with hepatocellular carcinoma (HCC), African Americans (AAs) and Asian/Pacific Islanders (APIs) are substantially less likely to undergo liver transplantation (LT) compared with whites. The authors examined whether disparities in the receipt of LT among LT-eligible HCC patients changed over a 10-year time period, and whether the disparities might be explained by sociodemographic or clinical factors. METHODS: The National Cancer Data Base, a national hospital-based cancer registry, was used to study 7707 adults with small (≤ 5 cm), nonmetastatic HCC diagnosed between 1998 and 2007. Racial/ethnic patterns in the use of LT were compared during 2 periods of 5 years each: 1998 through 2002 (n = 2412 patients) and 2003 through 2007 (n = 5295 patients). Data regarding comorbid medical conditions were only available during the later time period. RESULTS: Large and persistent racial/ethnic differences in the probability of receiving LT were observed. Compared with whites, hazard ratios (HRs) and associated 95% confidence intervals (95% CIs) for receiving LT from 1998 through 2002 were 0.64 (95% CI, 0.46-0.89) for AA patients, 1.01 (95% CI, 0.79-1.29) for Hispanic patients, and 0.52 (95% CI, 0.39-0.68) for API patients. Analogous results for 2003 through 2007 were 0.64 (95% CI, 0.54-0.76) for AA patients, 0.86 (95% CI, 0.75-0.99) for Hispanic patients, and 0.58 (95% CI, 0.49-0.69) for API patients. AA patients were less likely than whites to undergo any form of surgery, and API patients were more likely than whites to undergo surgical resection. Adjustment for sociodemographic and clinical factors produced only small changes in these HRs. CONCLUSIONS: Between 1998 and 2007, there were large and persistent racial/ethnic disparities noted in the receipt of LT among patients with HCC. These disparities were not explained by sociodemographic or clinical factors. Cancer 2011;. © 2011 American Cancer Society.

BACKGROUND: Concurrent chemoradiation therapy, the standard of care for locally advanced nonsmall cell lung cancer (NSCLC), can cause life-threatening pneumonitis and esophagitis. X-ray (photon)-based radiation therapy (RT) often cannot be given at tumoricidal doses without toxicity to proximal normal tissues. We hypothesized that proton beam therapy for most patients with NSCLC could permit higher tumor doses with less normal-tissue toxicity than photon RT delivered as 3-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT). METHODS: We compared the toxicity of proton therapy+concurrent chemotherapy in 62 patients with NSCLC (treatment period 2006-2008) with toxicity for patients with similar disease given 3D-CRT+chemotherapy (n = 74; treatment period 2001-2003) or IMRT+chemotherapy (n = 66; treatment period 2003-2005). Proton therapy to the gross tumor volume was given with weekly intravenous paclitaxel (50 mg/m2) and carboplatin (area under the curve 2 mg/mL/min). The primary endpoint was toxicity (Common Terminology Criteria for Adverse Events version 3.0). RESULTS: Median follow-up times were 15.2 months (proton), 17.9 months (3D-CRT), and 17.4 months (IMRT). Median total radiation dose was 74 Gy(RBE) for the proton group versus 63 Gy for the other groups. Rates of severe (grade ≥3) pneumonitis and esophagitis in the proton group (2% and 5%) were lower despite the higher radiation dose (3D-CRT, 30% and 18%; IMRT, 9% and 44%; P

From 1972 to 1986, 354 patients with local and locoregional adenocarcinoma of the prostate were treated with curative intent at the Medical College of Wisconsin. Fifty-six of these patients were found to have Stage D1 disease (evidence of pelvic lymph node involvement). Using external beam irradiation alone, these patients were treated aggressively to the pelvis followed by a boost to the prostate. The median dose to the prostate was 6800 cGy, and to the pelvis, it was 5040 cGy. The median period of observation after treatment was 9 years. Actuarial survival was 76% at 5 years, and disease-free survival was 61% at 5 years. Twenty-three patients had biopsy-proved pelvic lymph node involvement; the other 33 were considered to have Stage D1 disease based on abnormal computed tomographic scans, lymphangiograms, or both. Actuarial survival and disease-free survival were calculated for both groups separately, and there was no statistical difference in the results. Major complications occurred in 3.6% (two patients) of this group with Stage D1 disease. These results support the continued use of aggressive external beam irradiation in patients with locoregional adenocarcinoma of the prostate.

Hyperfractionated radiation therapy (HFX) attempts to overcome tumor proliferation during treatment by permitting higher total doses in the same overall time as standard fractionation. Whereas interruptions, including splits, reduce local control with standard fractionation in carcinoma of the upper respiratory and digestive tracts, HFX might compensate for interruptions. Patients were randomized to receive total doses of 6720, 7200, 7680, and 8160 cGy, using 120 cGy twice daily, 5 days per week. Those analyzed received +/- 4% of assigned total dose and lived 90 days or more. Treatment was completed within 5 days of the time specified for each treatment arm in 233 patients; 48, 80, and 131 patients had delays 14, 10, and 5 days or more, respectively. Locoregional control and survival were significantly (P less than or equal to 0.03) reduced with delays of 5 days or more when corrected for prognostic factors. Late effects of radiation therapy were not affected by interruptions. These data support the hypothesis that proliferation (possibly accelerated) of tumor clonogens during treatment influences the outcome.

The clinical course of patients with thymoma varies widely despite its histologically benign appearance. Treatment decisions are based on local invasion and the extent of resection. Because some patients have more aggressive tumors, the prognostic significance of flow cytometric (FCM) analysis of nuclear DNA content was examined. Adequate tissue from paraffin-embedded blocks was available for 25 patients. Using FCM, the percentage of cells in S-phase (%S) and the ploidy, based on the DNA index (DI), were determined. The mean patient age was 52 years, with a female-to-male ratio of 1.3:1 and a median follow-up of 64 months. Seventeen patients underwent total tumor resections, and 12 also received radiation therapy. Eight patients underwent subtotal resections, with five receiving radiation therapy (with or without chemotherapy) and three receiving chemotherapy alone. Based on invasion and intrathoracic dissemination, the tumors were classified into four stages. The mean %S was 5.6. There was no relationship observed between %S and patient outcome. The 5-year disease-free survival rate was 85% for the 16 patients with diploid (DI = 1) tumors and 33% for the 9 patients with aneuploid (DI more than 1) tumors (P less than 0.002). Similar significant differences were observed by stage and extent of surgery. For those who had total resection (n = 17), the disease-free survival rate was 89% when DI equaled 1 and 50% when DI was more than 1 (P = 0.01). Although the numbers studied were small, when stage, histologic findings, and type of surgery were subdivided by DI, a higher incidence of relapse was associated consistently with aneuploidy. The DI appears to be a useful prognostic parameter for identifying patients at high risk of relapse.

Since 1973, the Radiation Therapy Oncology Group (RTOG) has staged and stratified patients in non-small cell lung cancer (NSCLC) protocols according to the RTOG staging system. In 1985, the American Joint Committee on Cancer (AJCC) revised its lung cancer staging system, with the principle differences from the RTOG system being the staging of involvement of the chest wall and of contralateral mediastinal and hilar lymph nodes. To determine if the AJCC system discriminated outcome differently than the RTOG system in a nonoperative series, all 850 evaluable patients treated with hyperfractionated radiation therapy (RT) on the RTOG protocol 83-11 were restaged by the AJCC system. There was 67% agreement in patient distribution between the following comparable stages in each system: RTOG Stage II/AJCC Stage II; RTOG Stage III/AJCC Stage IIIA; and RTOG Stage IV/AJCC Stage IIIB. Both systems successfully predicted for survival (P less than 0.001), although the RTOG staging was more discriminating (relative risk ratios, 1.59 versus 1.38). Among the 507 favorable patients (those with less than or equal to 5% weight loss and Karnofsky performance status [KPS] of 70 to 100), the RTOG staging was also more predictive (P = 0.004 versus P = 0.01). When RTOG Stage III (462 patients) was divided into those without contralateral mediastinal or hilar adenopathy (AJCC Stage II/IIIA) and those with (AJCC Stage IIIB), a significant survival (P = 0.0001) was noted with 2-year survival rates of 26% versus 4%, respectively. When AJCC Stage IIIA (348 patients) was divided into the patients without chest wall invasion (RTOG Stage II/III) and those with (RTOG Stage IV), a difference in 2-year survival of 22% versus 10% was observed (P = 0.002). Although both staging systems independently predict for survival, a fusion of both staging systems is the most discriminating of outcome. Future nonoperative studies in locally advanced NSCLC should stratify for contralateral nodal involvement (per AJCC staging) and chest wall invasion (per RTOG staging).

BACKGROUND Mothers of children who have ataxia telangiectasia have been reported to be at increased risk for development of breast carcinoma. To test whether sequence variants in the ataxia telangiectasia, mutated, gene (ATM) are associated with breast carcinoma, the authors compared the frequency of ATM cDNA sequence changes in patients with breast carcinoma with the corresponding frequency in control patients. METHODS The authors sequenced ATM cDNA from 91 patients with breast carcinoma and compared the frequencies of sequence changes in these patients with the corresponding frequencies in a control sample of 940 individuals with no history of malignant disease. RESULTS Thirty-five patients with breast carcinoma had one or more single-base changes in ATM. Three genetic variants were found in at least two patients. These variants resulted in Asp1853Asn, Pro1054Arg, or Ser49Cys amino acid substitutions in the ATM protein. The Ser49Cys variant was more common in patients with breast carcinoma than in the control patients, with respective frequencies of 6.7% (5 of 75 patients) and 1.3% (12 of 940 patients; P = 0.006; Fisher two-sided exact test). The subgroup of patients with bilateral breast carcinoma had a Ser49Cys frequency of 11.8% (2 of 17 patients), which again was significantly different from what was observed in the control group (P = 0.024; Fisher two-sided exact test). The allele frequencies of the other two variants were not different between case patients and control patients. CONCLUSIONS Patients with breast carcinoma, particularly those with bilateral disease, were more likely to have a variant in the ATM gene that resulted in a Ser49Cys substitution in the gene product. Additional studies are needed to evaluate the potential functional consequences of the Ser49Cys substitution and confirm the relevance of this variant in the development of breast carcinoma. Cancer 2004;100:1345–51. © 2004 American Cancer Society.

BACKGROUND The current study was performed to determine the maximum tolerated dose (MTD), toxicity, and outcome of infusional 5 bromo-2'-deoxyuridine (bromodeoxyuridine; BUdR) given with accelerated fractionation whole brain radiation therapy (WBRT) after chemotherapy for the treatment of primary central nervous system lymphoma (PCNSL). METHODS Twelve patients with untreated and histologically confirmed PCNSL were entered on the study between 1994 and 1996. Chemotherapy was comprised of one course of IDHAP plus high-dose methotrexate (HD-MTX). IDHAP is comprised of idarubicin at a dose of 1.5 mg/m2/day × 4 days intravenously by continuous infusion (i.v. CI), dexamethasone at a dose of 40 mg i.v. on Days 1–5, cytosine arabinoside at a dose of 2000 mg/ m2 i.v. on Day 5 after cisplatin, and cisplatin at a dose of 25 mg/m2/day × 4 days i.v. CI. HD-MTX was given at a dose of 3.5 g/m2 i.v. between Day 10 and Day 14 after IDHAP. BUdR was given as an i.v. CI over 48 hours, 2–3 days prior to WBRT and then weekly during WBRT. Dose escalation started at 1.5 g/m2/day for Cohort 1 with subsequent increments of 0.3 g/m2/day. The WBRT dose was 45 grays (Gy) at a dose of 1.5 Gy twice a day, 5 days per week. Neurocognitive testing was performed before, during, and after treatment. RESULTS Nine of 12 patients entered on the study received BUdR. One of 3 patients in Cohort 1 developed leukoencephalopathy (LEP), a dose-limiting toxicity (DLT), within 2 months of the completion of therapy. Therefore, the next cohort received the same dose level. Because no toxicity was observed in Cohort 2, the third cohort received a BUdR dose of 1.8 g /m2/day. Shortly after completing enrollment in Cohort 3, 3 more patients developed LEP, including 2 from Cohort 1 who had received a dose of 1.5 g/m2/day. Thus, DLT occurred at a dose of 1.5 g/m2/day, the starting level in the current study. As a result, the trial was stopped. Eight of 12 patients achieved a complete response, 3 achieved a partial response, and 1 patient died before response assessment. CONCLUSIONS Hyperfractionated WBRT with concurrent BUdR after chemotherapy was found to result in modest disease control but has unacceptable neurotoxicity. Cancer 2003;98:1021–8. © 2003 American Cancer Society. DOI 10.1002/cncr.11627

BACKGROUND The relative importance of prognostic factors in patients with early-stage Hodgkin disease remains controversial. The purpose of this study was to evaluate prognostic factors among patients who received chemotherapy before radiotherapy. METHODS From 1987 to 1995, 217 consecutive patients ranging in age from 16 to 88 years (median, 28 years) with Ann Arbor Stage I (n = 55) or II (n = 162) Hodgkin disease underwent chemotherapy before radiotherapy at a single center. Most were treated on prospective studies. Patients received a median of three cycles of induction chemotherapy. Mitoxantrone, vincristine, vinblastine, and prednisone (NOVP), doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), cyclophosphamide, vinblastine, procarbazine, prednisone, doxorubicin, bleomycin, dacarbazine, and CCNU (CVPP/ABDIC), or other chemotherapeutic regimens were given to 160, 18, 15, 10, and 14 patients, respectively. The median radiotherapy dose was 40 Gy. Serum β-2-microglobulin (β-2M) levels ranged from 1.0 to 4.1 mg/L (median, 1.7 mg/L; upper limit of normal, 2.0 mg/L). We studied univariate and multivariate associations between survival and the following clinical features: serum β-2M level above 1.25 times the upper limit of normal (n = 12), male gender (n = 113), hypoalbuminemia (n = 11), and bulky mediastinal disease (n = 94). RESULTS Follow-up of surviving patients ranged from 0.9 to 13.4 years (median, 6.6 years) and 92% were observed for 3.0 or more years. Nineteen patients have died. Only elevation of the serum β-2M level was an independent adverse prognostic factor for overall survival (P = 0.0009). CONCLUSIONS The prognostic significance of a simple, widely available, and inexpensive blood test, β-2M, has not been studied routinely in patients with Hodgkin disease and should be tested prospectively in large, cooperative group trials. Cancer 2002;95:2534–8. © 2002 American Cancer Society. DOI 10.1002/cncr.10998

Total body irradiation (TBI) is commonly used with autologous bone marrow transplantation (BMT) for treatment of hematologic malignancies. Pulmonary complications of TBI can cause long-term morbidity and mortality. The authors have compared the pulmonary toxicity and efficacy of two different TBI fractionation regimens in otherwise identical autologous BMT protocols.Between 1990 and 1997 patients younger than 60 years of age with low-grade lymphoma at high risk of treatment failure were enrolled on one of two sequential protocols for autologous BMT differing only in their TBI regimens. The preoperative chemotherapy regimens were identical and consisted of intravenous etoposide (1500 mg/m(2)) for 1 day, intravenous cyclophosphamide (60 mg/kg) for 2 days, and mesna (10 mg/kg). The TBI used in protocol A consisted of twice-daily fractions of 1.7 grays (Gy) for 3 days to a total of 10.2 Gy through lateral fields, with no lung shielding. In protocol B, the TBI consisted of 3 Gy once daily for 4 days to a total of 12 Gy through anteroposterior fields, with lung shielding (5 half-value layers) during the third dose. Fifty-eight patients were treated on protocol A and 24 on protocol B. The groups were equivalent with regard to age, performance status (PS) and gender. Lung function was assessed objectively by pulmonary function tests (PFTs) before and at intervals after TBI. The pulmonary function parameters assessed included forced vital capacity (FVC), forced expiratory volume in 1 second (FEV(1)), forced expiratory flow between 25% and 75% of vital capacity (FEF(25-75)), diffusing capacity for carbon monoxide (DL(CO)), and total lung capacity (TLC). Each patient's post-TBI PFTs were normalized to the corresponding pre-TBI values and analyzed using a random effects model. Clinical pulmonary function status was scored according to Radiation Therapy Oncology Group criteria for acute and late lung toxicity. All clinical pulmonary toxicities such as pneumonitis, pneumonia, and diffuse alveolar hemorrhage, whether specifically related to TBI or not, were scored. Toxicity was classified as either acute (i.e., occurring within 90 days of TBI) or late (i.e., occurring more than 90 days after TBI). The endpoints of analysis were overall survival (OS), freedom from progression, and chronic pulmonary toxicity. Survival, progression, and complication free survival were computed using the method of Kaplan and Meier.Three-year actuarial OS rates were 66% and 67% for protocols A and B, respectively. Patients 50 years of age or older had a hazard ratio of death 3.5 times higher than younger patients. Freedom from progression was significantly different for the 2 TBI regimens (P0.001; log-rank test): 31% at 3 years in the protocol A group compared with 82% in protocol B group. Patients on protocol A had a rate of progression 4.7 times higher than patients on protocol B. The TBI protocols did not differ significantly in their effects on FVC, FEV(1), FEF(25-75), DL(CO), and TLC. Patients 45 years of age or older had lower average posttransplant values of FEV(1), FVC, and DL(CO) than younger patients. There was no significant difference in acute or late toxicity rates between patients on the two protocols. Seven of the 57 patients in the twice-daily TBI (protocol A) group had acute pulmonary events (Grade 3 or greater), compared with 6 of the 24 patients in the once-daily (protocol B) group (P = 0.19). The 3-year freedom from late complications rate was 80% in the protocol A group and 70% in the protocol B group (P = 0.45). Patients with a PS of 1 had a hazard ratio of late complications 3.2 times greater than patients with a PS of 0 (P0.001).It is possible to intensify TBI from a total dose of 10.2 Gy delivered in 6 twice-daily fractions to 12 Gy delivered in 4 once-daily fractions without significantly increasing the risk of pulmonary toxicity. The increased dose may contribute to a decrease in the recurrence rate in these patients. (c) 2001 American Cancer Society.

The authors previously reported that central lymphatic irradiation (CLI) can induce molecular remission in patients with Stage I-III follicular lymphoma, as measured by polymerase chain reaction analysis for t(14;18) (q32;q21). Hematologic toxicity has been considered a major consequence of CLI. This study was undertaken to analyze the patterns of hematologic recovery after CLI.Thirty-three patients with Stage I-III follicular lymphoma were treated with CLI between January 1993 and February 1998. CLI consisted of irradiation to mantle, upper two-thirds of abdomen, and pelvic fields. Each field was treated to 30.0-30.6 grays (Gy) at 1.5-1.8 Gy per fraction, with a boost to 36.0-39.6 Gy at the same rate to the sites of macroscopic disease. A break of approximately 4 weeks was given after treatment of each field. Twenty-four patients who were followed for a minimum of 1 year from the end of CLI form the basis of this analysis. Fourteen patients were male. Three patients had Stage I disease, 6 patients had Stage II disease, and 15 patients had Stage III disease. The International Prognostic Index (IPI) for malignant lymphoma was 0 for 5 patients, 1 for 13 patients, and 2 for 6 patients. The Eastern Cooperative Oncology Group performance status was 0 for 21 patients and 1 for 3 patients. The median values for their pretreatment characteristics were as follows: age, 60 years (range, 34-73 years); height, 173 cm (range, 155-193 cm); weight, 79 kg (range, 57-107 kg); body surface area (BSA), 1.95 m(2) (range, 1.61-2.31 m(2)); bone marrow cellularity, 27%(range, 2-75%), platelet count, 233,000/mm(3) (range, 139,000-339,000/mm(3)), white blood cell (WBC) counts, 6400/mm(3) (range, 4200-10,900/mm(3)); and hemoglobin, 14.5 mg/dL (range, 11.8 -16.6 mg/dL). The median duration of CLI was 159 days (range, 137-345 days). Ten patients had cardiovascular disease. The number of sites receiving a boost dose ofor = 36.0 Gy was 0 sites in 1 patient, 1 site in 6 patients, 2 sites in 11 patients, 3 sites in 5 patients, and 4 sites in 1 patient. The platelet, hemoglobin, and WBC counts were followed every 3 months after completion of CLI. These counts were normalized to the pretreatment counts for statistical analyses. Univariate and multivariate analyses were performed to investigate the correlations between patient factors and hematologic status at 1 year posttreatment. Pearson correlation analysis was used for the continuous factors (patient age, height, weight, BSA, bone marrow cellularity, and duration of CLI), and the Mann-Whitney test was used for categoric factors (IPI, gender, performance status, stage, number of sites receivingor = 36.0 Gy, and presence or absence of cardiovascular disease).There was continued recovery, essentially approaching the pretreatment levels, over 3 years for platelet, WBC, and hemoglobin counts. Factors that were associated significantly with normalized platelet counts at 1 year by univariate analyses were age (P = 0.015) and cardiovascular disease (P = 0.041). Age was the only significant factor by multivariate analyses, with older patients having lower platelet counts at 1 year posttreatment. No factors were found that were associated significantly with 1-year normalized WBC or hemoglobin levels by either univariate or multivariate analyses.All three of the hematologic components (platelets, WBC, and hemoglobin) essentially recover after patients undergo CLI over a 3-year period. Older age was the only significant adverse factor that affected the platelet recovery, as detected by multivariate analysis. (c) 2001 American Cancer Society.

Although surgery is considered standard therapy for unicentric Castleman disease, favorable responses to radiotherapy also have been documented. The authors undertook this study to analyze the clinical factors, treatment approaches, and outcomes of patients with unicentric or multicentric Castleman disease, and to report the outcomes of patients with unicentric Castleman disease treated with radiotherapy.The authors reviewed the medical records of 22 patients who had received a histologic diagnosis of Castleman disease at the University of Texas M. D. Anderson Cancer Center between 1988 and 1999. One patient with a concurrent histopathologic diagnosis of nonsecretory multiple myeloma was excluded from the study. In all patients, the diagnosis of Castleman disease was based on the results of lymph node biopsies. Disease was categorized as being either unicentric or multicentric and further subdivided into hyaline vascular, plasma cell, or mixed variant histologic types. Clinical variables and outcomes were analyzed according to treatment, which consisted of surgery, chemotherapy, or radiotherapy.Records from 21 patients were analyzed: 12 had unicentric disease, and 9 had multicentric disease. The mean follow-up time for the entire series was 51 months (median, 40 months). Four patients with unicentric disease were treated with radiotherapy alone: 2 remain alive and symptom free, 2 died of causes unrelated to Castleman disease and had no evidence of disease at last follow-up. Eight patients with unicentric disease were treated with complete or partial surgical resection, and all are alive and asymptomatic. All nine patients with multicentric disease were treated with combination chemotherapy: five are alive with no evidence of disease, and four are alive with progressive disease.Surgery results in excellent rates of cure in patients with unicentric Castleman disease; radiotherapy can also achieve clinical response and cure in selected patients. Multicentric Castleman disease is a more aggressive clinical entity and is most effectively treated with combination chemotherapy, whereas the role of radiotherapy in its treatment remains unclear.

In the current study, the authors analyzed prognostic factors in patients with aggressive lymphoma treated with a chemotherapy regimen comprised of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without radiotherapy.Between September 1988 and December 1996, 294 patients with newly diagnosed, clinical Ann Arbor Stage I-IV, aggressive lymphoma were enrolled on 2 protocols at The University of Texas M. D. Anderson Cancer Center. Patients on these studies had a relatively favorable prognosis; 100% had M. D. Anderson tumor scoresor= 2 and 95%% had International Prognostic Indices (IPIs)or= 2. Treatment was comprised of 5 +/- 1 (mean +/- the standard deviation) cycles of CHOP chemotherapy with or without involved-field radiotherapy to a total dose of 40.1 +/- 3.3 grays (mean +/- the standard deviation).The median length of follow-up was 61 months. Three factors were found to retain independent prognostic significance on multivariate analysis in terms of progression-free survival:1 extranodal site of disease (P0.001), bulky disease (or= 7 cm) (P = 0.005), and an at least 10% elevation in the serum lactate dehydrogenase (LDH) level (P = 0.007). Patient age60 years (P = 0.001), bulky disease (P = 0.016), and an at least 10% elevation in the serum LDH level (P = 0.040) also were found to be independent prognostic factors for overall survival.The independent prognostic factors in the current study suggest that either the M. D. Anderson tumor score system or the IPI can be used to select which aggressive lymphoma patients are at high risk for disease recurrence based on their having more than two adverse factors and who consequently are candidates for more intensive frontline therapy. Involved-field radiotherapy should be considered in those patients with bulky lymphomas.

The current study was undertaken to define the natural history and patterns of failure of localized non-Hodgkin lymphoma (NHL) involving the thyroid gland.A retrospective review of 51 patients with Ann Arbor Stage I or II NHL involving the thyroid gland was performed. The median age of the patients was 59 years. There were 33 females. There were 21 patients with Stage I disease and 30 patients with Stage II disease. The International Prognostic Index (IPI) was known for 43 patients (it was 0 in 16 patients andor = 1 in 27 patients). Fifteen patients had mediastinal involvement. Four patients underwent thyroidectomy, 18 patients received radiation therapy, 5 patients received chemotherapy, and 24 patients received combined modality therapy (CMT) with chemotherapy and radiation therapy. Treatment modality, patient gender, IPI, disease stage, and mediastinal involvement were examined for significance with regard to overall survival (OS) and failure free survival (FFS).The 5-year OS and FFS rates were 64% and 76%, respectively. The 5-year FFS rates by treatment regimen were 76% for radiation therapy, 50% for chemotherapy, and 91% for CMT (P = 0.15). IPI was found to be the only significant predictor of OS. The 5-year OS rates were 86% and 50%, respectively, for IPIs of 0 andor = 1 (P = 0.02). None of the 5 variables were found to correlate significantly with FFS, although the 5-year FFS rates were 93% and 68%, respectively, for IPIs of 0 andor = 1 (P = 0.08). Eleven patients failed treatment. Nine patients had a component of distant failure across the diaphragm.The prognosis of patients with localized NHL involving the thyroid gland appears to be very good, especially when CMT is used. Distant recurrences appear to account for the majority of treatment failures. The IPI was found to be a significant prognostic factor for OS and a marginal one for FFS.

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.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.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.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.

Lymphoma of the nasal cavity and paranasal sinuses is a rare presentation of extranodal lymphoma with a natural history that is not well characterized in this era of combination chemotherapy. The goals of this retrospective study were 1) to define the natural history of sinonasal lymphomas; 2) to compare the results of radiation therapy (XRT) alone with those of combined modality therapy (CMT) in the treatment of patients with lymphoma of the nasal cavity and paranasal sinuses; and 3) to define prognostic factors for each treatment.Between 1947 and 1993, 70 patients with newly diagnosed lymphoma of the nasal cavity and paranasal sinuses were treated. The Ann Arbor stages were: Stage IE: 42 patients; Stage IIE: 14 patients; Stage IIIE: 2 patients; and Stage IV: 12 patients. The distribution of T classifications of the primary tumors was as follows: T1: 2 patients; T2: 16; T3: 18; and T4: 34. Greater than 90% of the patients had intermediate grade lymphoma (Working Formulation), and none had follicular lymphoma. Twenty-eight patients received XRT alone, and 42 received CMT.The actuarial 5-year freedom from progression (FFP) and overall survival (OS) rates for the entire group were 57% and 52%, respectively. For patients with localized disease (Stages IE and IIE) receiving CMT, the actuarial 5-year FFP and OS were 83% and 67%, respectively. In multivariate analysis, treatment with CMT (P = 0.0005) and stage (IE vs. IIIE-IV) (P = 0.0001) were associated with improved FFP. In the group of patients receiving XRT, extent of disease (Stage IE, T1-3 vs. Stage IE, T4 vs. Stage IIE-IV) (P = 0.0001) was the only clinical characteristic associated with improved FFP in multivariate analysis. For patients receiving CMT, International Index (0 vs. 1-3 vs. 4, 5) (P = 0.0001) was the only significant factor predictive of improved FFP in multivariate analysis. One patient failed in the central nervous system (CNS) after initial therapy as a result of a radiation therapy marginal miss.In a Western population, patients with localized lymphoma of the nasal cavity and paranasal sinuses have a favorable prognosis when treated with CMT. FFP is significantly improved by treatment with CMT. For patients treated with XRT, extent of disease is the strongest predictor of outcome. International Index is the most significant prognostic factor for patients receiving CMT. Failure in the CNS is rare after initial therapy and is associated with local failure.

A survival difference between white and black females has been reported after diagnosis and treatment for breast carcinoma. Although multivariate analyses demonstrate that the survival difference is less or nonexistent when additional prognostic factors are considered, study results have been inconsistent. The objective of this study was to examine further the role of ethnicity as an independent prognostic factor for breast carcinoma survival among white and black females treated over a 30-year period.Among 3382 eligible white and black females who registered at M. D. Anderson Cancer Center (MDACC) from 1958 to 1987, ethnicity, age, socioeconomic status (SES), stage of disease, and treatment were examined. Data were obtained from the hospital tumor registry and survival was compared using actuarial life tables and multivariate Cox regression analyses.Univariate analyses demonstrated that the survival difference between white and black females was significant, with black females having a 1.63 times higher risk of mortality at 5 years compared with white females (confidence interval (CI), 1.47-1.82), with ethnicity a significant predictor of survival (P0.001). After controlling for SES, stage, and treatment, the relative risk was 1.12 (CI, 1.00-1.25) and ethnicity was no longer a strong predictor of survival (P = 0.048).In this hospital population, the white and black female survival difference, which was highly significant when only univariate analyses were considered, became marginally significant after controlling for other prognostic factors.

Primary lymphomas of the uterus or cervix are so rare that treatment series of single institutions consist of very small numbers of patients, making standard treatment difficult to define. The outcome of patients treated with a combination of chemotherapy and radiation therapy was analyzed for all but patients with the most advanced disease.From 1976 to 1992, 16 patients received definitive treatment. Thirteen patients had intact uteri (group 1) and 3 presented with paracolpal lymphomas after previous hysterectomies (group 2). Twelve of the patients received chemotherapy and external irradiation. The remaining four underwent only chemotherapy. The overall survival and freedom from disease progression were analyzed according to Kaplan-Meier methods. Prognoses were related to the International Index, Ann Arbor stage, and International Federation of Gynecology and Obstetrics stage.Five-year survival and freedom from disease progression were 77% and 67%, respectively, for group 1, and all patients in group 2 were cured. A statistically significant correlation of survival with scores of the International Index was found in group 1. For patients with scores in the low or low-intermediate range (n = 10), 5-year survival was 90%. All patients who scored in the high-intermediate or high range (n = 3) died by 66 months after their diagnosis (P = 0.0153). The Ann Arbor stage had less predictive value, with 5-year survival of 89% for Stage I and II patients (n = 9), compared with 50% survival for the four Stage III and IV patients (P = 0.0701). International Federation of Gynecology and Obstetrics staging did not predict outcome.The combination of chemotherapy and irradiation is the most effective treatment regimen for all uterine and cervical lymphomas. The International Index is most predictive of outcome.

Follicular lymphoma is a clearly defined type of malignant lymphoma. The many treatment approaches reported in the literature attest to the lack of agreement on its best management. The treatment experiences of patients with Stage I or II follicular lymphoma who were at risk for at least 5 years were reviewed to assess their survival, disease free survival, and patterns of failure.Between 1974 and 1988, 144 patients with Stage I or II follicular lymphoma were treated at The University of Texas M. D. Anderson Cancer Center. Initial staging studies included lymphangiography in 87% of the patients, computerized tomography of the abdomen and pelvis in 60%, bone marrow biopsy in 98%, and diagnostic or staging laparotomy in 33%. Forty-five patients were treated with regional radiotherapy, 84 patients with combined chemotherapy and radiotherapy, and 15 patients were treated with chemotherapy alone.With a median follow-up of 8.7 years (range, 48-182 months) the actuarial survival rates at 5, 10, and 15 years were 81, 69, and 63%, respectively. The freedom from relapse (FFR) rates were 66, 56, and 46%, respectively. The FFR rate was better for patients treated with chemotherapy-radiotherapy than for patients treated with radiotherapy alone (63 vs. 35% at 15 years). In addition, there were no relapses after 7.5 years in patients treated with chemotherapy-radiotherapy, but relapses continued even beyond 15 years in patients treated with radiotherapy alone. Univariate analysis for each of the treatment groups revealed age to be the only significant prognostic factor. There was no significant difference in survival or disease free survival rates for the three histologic subtypes of follicular lymphoma.The addition of chemotherapy to radiotherapy may have increased the probability of cure for patients with Stages I or II follicular lymphoma.

The authors retrospectively analyzed 87 patients with malignant thymoma treated at M.D. Anderson Cancer Center between 1951 and 1990. The analysis examined the clinical stages, histologic types, and treatment modalities and attempted to determine if chemotherapy had an impact on survival.The patients were divided into three groups by their year of treatment and treatment modality. Patients treated between 1951 and 1975 were in Group I; patients treated between 1976 and 1980 were in Group II; and patients treated between 1981 and 1990 were in Group III. Most of the patients (18 [72%] in Group I; 16 [62%] in Group II; and 18 [50%] in Group III) had surgical resection alone or with radiotherapy. Patients with advanced-stage disease in Group I received single-agent chemotherapy, whereas patients with advanced-stage disease in Group II received a different, combination chemotherapy regimen, and those in Group III were treated primarily with cisplatin- and doxorubicin-based combination chemotherapy, e.g., the cyclophosphamide doxorubicin, and cisplatin with or without prednisone. The 17 patients treated with cisplatin with or without prednisone were separately evaluated for survival according to their response.Twenty-eight patients (5 [20%] in Group I; 6 [23%] in Group II; and 17 [47%] in Group III) received chemotherapy alone or after surgery or radiotherapy. The cisplatin with or without prednisone regimen was used in 17 Group III patients for initial treatment or for relapse. The overall response rate among the patients receiving the cisplatin with or without prednisone regimen was 64%; 6 (35%) had a complete response, and 5 (29%) had a partial response. Thirty-one (36%) of the 87 total patients had 45 recurrent tumors; the lung (29%), pleura (22%), and mediastinum (18%) were the most common sites of recurrence, whereas bone was the most common distant metastatic site. The 5-year survival rate was 70% in patients with Stage I disease, 71% in patients with Stage II or III disease, and 46% in patients with Stage IV disease. The 10-year survival rate was 70% in patients with Stage I disease, 47% in patients with Stage II or III disease, and 21% in patients with Stage IV disease. Statistical analysis indicated a significant difference among the survival rates of patients with noninvasive Stage I, invasive Stage II plus III (P = 0.033), and Stage II plus III and IV tumors (P = 0.056), but not between patients with Stage II or III tumors. Patients with a major response to the cisplatin with or without prednisone regimen had a significant survival improvement compared to those with no response (P = 0.002, log-rank test).Because thymoma is a chemosensitive tumor and frequently recurs in patients with Stage II or greater disease, chemotherapy carries a potential survival benefit and should be incorporated into the multimodality approach to prolong disease-free survival.

From 1972 to 1986, 354 patients with local and locoregional adenocarcinoma of the prostate were treated with curative intent at the Medical College of Wisconsin. Fifty-six of these patients were found to have Stage D1 disease (evidence of pelvic lymph node involvement). Using external beam irradiation alone, these patients were treated aggressively to the pelvis followed by a boost to the prostate. The median dose to the prostate was 6800 cGy, and to the pelvis, it was 5040 cGy. The median period of observation after treatment was 9 years. Actuarial survival was 76% at 5 years, and disease-free survival was 61% at 5 years. Twenty-three patients had biopsy-proved pelvic lymph node involvement; the other 33 were considered to have Stage D1 disease based on abnormal computed tomographic scans, lymphangiograms, or both. Actuarial survival and disease-free survival were calculated for both groups separately, and there was no statistical difference in the results. Major complications occurred in 3.6% (two patients) of this group with Stage D1 disease. These results support the continued use of aggressive external beam irradiation in patients with locoregional adenocarcinoma of the prostate.

Hyperfractionated radiation therapy (HFX) attempts to overcome tumor proliferation during treatment by permitting higher total doses in the same overall time as standard fractionation. Whereas interruptions, including splits, reduce local control with standard fractionation in carcinoma of the upper respiratory and digestive tracts, HFX might compensate for interruptions. Patients were randomized to receive total doses of 6720, 7200, 7680, and 8160 cGy, using 120 cGy twice daily, 5 days per week. Those analyzed received +/- 4% of assigned total dose and lived 90 days or more. Treatment was completed within 5 days of the time specified for each treatment arm in 233 patients; 48, 80, and 131 patients had delays 14, 10, and 5 days or more, respectively. Locoregional control and survival were significantly (P less than or equal to 0.03) reduced with delays of 5 days or more when corrected for prognostic factors. Late effects of radiation therapy were not affected by interruptions. These data support the hypothesis that proliferation (possibly accelerated) of tumor clonogens during treatment influences the outcome.

The clinical course of patients with thymoma varies widely despite its histologically benign appearance. Treatment decisions are based on local invasion and the extent of resection. Because some patients have more aggressive tumors, the prognostic significance of flow cytometric (FCM) analysis of nuclear DNA content was examined. Adequate tissue from paraffin-embedded blocks was available for 25 patients. Using FCM, the percentage of cells in S-phase (%S) and the ploidy, based on the DNA index (DI), were determined. The mean patient age was 52 years, with a female-to-male ratio of 1.3:1 and a median follow-up of 64 months. Seventeen patients underwent total tumor resections, and 12 also received radiation therapy. Eight patients underwent subtotal resections, with five receiving radiation therapy (with or without chemotherapy) and three receiving chemotherapy alone. Based on invasion and intrathoracic dissemination, the tumors were classified into four stages. The mean %S was 5.6. There was no relationship observed between %S and patient outcome. The 5-year disease-free survival rate was 85% for the 16 patients with diploid (DI = 1) tumors and 33% for the 9 patients with aneuploid (DI more than 1) tumors (P less than 0.002). Similar significant differences were observed by stage and extent of surgery. For those who had total resection (n = 17), the disease-free survival rate was 89% when DI equaled 1 and 50% when DI was more than 1 (P = 0.01). Although the numbers studied were small, when stage, histologic findings, and type of surgery were subdivided by DI, a higher incidence of relapse was associated consistently with aneuploidy. The DI appears to be a useful prognostic parameter for identifying patients at high risk of relapse.

Since 1973, the Radiation Therapy Oncology Group (RTOG) has staged and stratified patients in non-small cell lung cancer (NSCLC) protocols according to the RTOG staging system. In 1985, the American Joint Committee on Cancer (AJCC) revised its lung cancer staging system, with the principle differences from the RTOG system being the staging of involvement of the chest wall and of contralateral mediastinal and hilar lymph nodes. To determine if the AJCC system discriminated outcome differently than the RTOG system in a nonoperative series, all 850 evaluable patients treated with hyperfractionated radiation therapy (RT) on the RTOG protocol 83-11 were restaged by the AJCC system. There was 67% agreement in patient distribution between the following comparable stages in each system: RTOG Stage II/AJCC Stage II; RTOG Stage III/AJCC Stage IIIA; and RTOG Stage IV/AJCC Stage IIIB. Both systems successfully predicted for survival (P less than 0.001), although the RTOG staging was more discriminating (relative risk ratios, 1.59 versus 1.38). Among the 507 favorable patients (those with less than or equal to 5% weight loss and Karnofsky performance status [KPS] of 70 to 100), the RTOG staging was also more predictive (P = 0.004 versus P = 0.01). When RTOG Stage III (462 patients) was divided into those without contralateral mediastinal or hilar adenopathy (AJCC Stage II/IIIA) and those with (AJCC Stage IIIB), a significant survival (P = 0.0001) was noted with 2-year survival rates of 26% versus 4%, respectively. When AJCC Stage IIIA (348 patients) was divided into the patients without chest wall invasion (RTOG Stage II/III) and those with (RTOG Stage IV), a difference in 2-year survival of 22% versus 10% was observed (P = 0.002). Although both staging systems independently predict for survival, a fusion of both staging systems is the most discriminating of outcome. Future nonoperative studies in locally advanced NSCLC should stratify for contralateral nodal involvement (per AJCC staging) and chest wall invasion (per RTOG staging).

From 1965 through 1980, 193 patients with histologically proven endometrial carcinoma, FIGO-AJC Stage I-III, received preoperative radiation therapy. One hundred forty-two patients had Stage I (G1:41, G2:68, G3:33), 47 Stage II, and 4 Stage III endometrial carcinoma. All patients were treated with preoperative radiation therapy (intracavitary application, external pelvic irradiation or both) followed by total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO). They were followed from 3 to 18 years (median, 6.2 years) after the completion of the treatment and none was lost to follow-up. Overall 5-year actuarial disease-free survival was 85%. The interval between the completion of radiation therapy and TAH-BSO ranged from 3 days to 123 days (median, 40 days). Five-year and 10-year survivals were 95% among 65 patients who did not have residual cancer in the hysterectomy specimen compared to 75% and 70%, respectively, among 128 patients who had positive hysterectomy specimens (P less than 0.01). The presence or absence of residual carcinoma in the surgical specimen after preoperative irradiation was the only important prognostic variable. The most significant factors associated with residual cancer cells were the interval from the completion of radiation therapy to TAH-BSO (P less than 0.001) and the method of preoperative irradiation in patients with Stage I Grade 3 and Stage II external pelvic irradiation was less frequently associated with residual cancer than intracavitary applications (P = 0.043). With one exception, all patients who failed had residual cancer in the hysterectomy specimen. The depth of myometrial invasion of residual tumor in the hysterectomy specimen after preoperative irradiation was correlated to the frequency of failures (P = less than 0.05). Failures were distributed equally among the pelvis, para-aortic nodes, and distant sites. Complications of treatment were infrequent (7%) and were mild; no fatal complications were seen. The data suggest an optimal interval for hysterectomy is 29 to 42 days after completion of radiation therapy in unfavorable carcinomas of the endometrium. These patients also benefit from external pelvic irradiation with or without intracavitary applications as this therapy provides the highest probability there will be no residual cancer cells in the surgical specimen.

Three patients with primary malignant lymphoma of the uterine cervix are reported and the literature is reviewed. All of the patients in the current cases presented with irregular menstruation. Two patients were found to have diffuse histiocytic lymphoma, and one patient had diffuse mixed lymphoma. Histologic diagnosis was confirmed by outside expert pathologists in all cases. In spite of locally advanced disease according to FIGO's classification (Stage IVA-2 and Stage IIB-1), they responded well to external irradiation, and had control of tumor within the pelvis. All are alive at 13, 7, and 3 years, respectively, after the completion of irradiation. One patient developed disseminated disease 4.25 years after the completion of external irradiation, but was successfully treated with combination chemotherapy for 2 years, and is alive at 6.75 years after the completion of chemotherapy without disease. Review of the other 21 cases reported in the literature reveals that 14 were free of disease after treatment. The importance of distinguishing malignant lymphoma from undifferentiated carcinoma or sarcoma is emphasized since cervical malignant lymphoma can be successfully treated with irradiation in spite of locally advanced disease.

The malignant germinal tumors found in the testis (seminoma, teratocarcinoma, embryonal carcinoma, choriocarcinoma, and mixtures of these) can originate in the anterior mediastinum. An occult testicular tumor must be sought, but primary mediastinal germinal tumors constitute a true entity. The details of 24 such patients treated at Walter Reed General Hospital are presented. Of 19 patients who died, 2 were women; postmortem examination of the testes of 13 men failed to reveal a primary tumor. Five patients are alive and well with no testicular abnormality. It is important to distinguish the histopathologic types. Seminomas are readily controlled with modest doses of irradiation. Embryonal carcinomas are also radiocurable with somewhat higher doses; 2 long-term disease-free survivors are reported. Teratocar-cinomas are highly malignant and require higher doses for control. Choriocar-cinomas progress so rapidly that chemotherapy is necessary.

This is a final report on the treatment of 346 patients entered in the Protocol 13L. The study was activated March 1972, and closed for the patient accession March 1975. All patients had a histologic or cytologic diagnosis of primary lung cancer limited disease. Limited disease was defined by VALG as a tumor involving one hemithorax without evidence of pleural effusion or distant metastases. Patients were randomized into two groups, radiotherapy alone or radiotherapy with CCNU and hydroxyurea. Both groups received the same dose of radiotherapy, which was given in the same fashion (5000 to 6000 rads given in 28 to 42 days). The chemotherapy program was: CCNU-100 mg/m2, orally every six weeks and Hydroxyurea-1 g/m2 orally twice a week. Chemotherapy demonstrated an early benefit in small cell carcinoma with 18 weeks extension of the median survival (p = 0.07). However, among patients surviving beyond the median survival, radiotherapy alone was the most effective treatment. At 24 months, 15% of the patients were alive in the radiotherapy alone group, versus 7% in the radiotherapy-chemotherapy group (p = 0.02). Chemotherapy did not modify the appearance time, pattern of, or survival after the first evidence of metastasis. Local toxicity of radiotherapy was not increased by chemotherapy. Severe or life threatening hematologic toxicity was present in one of every four patients at the end of radiotherapy. Those patients who developed moderate and severe hematologic toxicity at the end of radiotherapy survived longer than the patients who experienced mild toxicity or no toxicity (p = 0.03). The performance status effect seen early had disappeared at 10 weeks. In long-term survivors, no common factors could be identified except that more patients in the radiotherapy alone group are surviving from all cell types (p = 0.02).