Induction chemotherapy plus three-dimensional conformal radiation therapy in the definitive treatment of locally advanced non-small-cell lung cancer

PURPOSE: To evaluate our institution's experience using chemotherapy in conjunction with three-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS: From 1991 to 1998, 152 patients with Stage III non-small-cell lung cancer (NSCLC) were treated with 3D-CRT at Memorial Sloan-Kettering Cancer Center. A total of 137 patients (90%) were surgically staged with either thoracotomy or mediastinoscopy. The remainder were staged radiographically. Seventy patients were treated with radiation therapy alone, and 82 patients received induction chemotherapy before radiation. The majority of chemotherapy-treated patients received a platinum-containing regimen. Radiation was delivered with a 3D conformal technique using CT-based treatment planning. The median dose in the radiation alone group was 70.2 Gy, while in the combined modality group, it was 64.8 Gy. RESULTS: The median follow-up time was 30.5 months among survivors. Stage IIIB disease was present in 36 patients (51%) in the radiation-alone group and 57 patients (70%) in the combined-modality group. Thirty-nine patients had poor prognostic factors (KPS < 70 or weight loss > 5%), and they were equally distributed between the two groups. The median survival times for the radiation-alone and the combined-modality groups were 11.7 months and 18.1 months, respectively (p = 0.001). The 2-year rates of local control in the radiation-alone and combined-modality groups were 35.4% and 43.1%, respectively (p = 0.1). Grade 3 or worse nonhematologic toxicity occurred in 20% of the patients receiving radiation alone and in 16% of those receiving chemotherapy and radiation. Overall, there were only 4 cases of Grade 3 or worse esophagitis. CONCLUSION: Despite more Stage IIIB patients in the combined-modality group, the addition of chemotherapy to 3D-CRT produced a survival advantage over 3D-CRT alone in Stage III NSCLC without a concomitant increase in toxicity. Chemotherapy thus appears to be beneficial, even in patients who are receiving higher doses of radiation therapy than are typically given with conventional techniques. Because locoregional failure remains a major challenge in patients with advanced disease, 3D-CRT in conjunction with chemotherapy may allow safe treatment to the dose levels required to further enhance local control.     

Treatment of pediatric Hodgkin's disease with chemotherapy alone or combined modality therapy

Optimal treatment for Hodgkin's disease during childhood is unknown. We report the treatment outcome of patients with Hodgkin's disease <13 years of age seen at the American University of Beirut Medical Center (AUBMC) between 1980 and 1996. A retrospective review of the medical records of 24 children treated for HD at AUBMC was performed. Treatment consisted of chemotherapy alone (n = 15) or chemotherapy plus involved field radiotherapy (n = 9). Chemotherapy consisted of COPP, ABVD, or alternating cycles of each for a total of 6 to 12 cycles, depending on clinical and radiological response; three patients received MOPP. Five patients in the chemotherapy group had clinical stage (CS) I and II and 10 had CS III disease. In the combined modality group, eight patients had CS I and II and one had CS IV disease. At a median follow-up of 5 years, the event-free survival (EFS) for the combined modality group was 100% and the overall survival (OS) 100%. For the chemotherapy alone group, the EFS was 56% and the OS was 79%. Four patients (27%) in the chemotherapy alone group who had Stage IIIB disease relapsed. Mean time to relapse was 4.3 years. In our experience, six cycles of COPP or (COPP plus ABVD) alone were suboptimal for the treatment of Stage IIIB Hodgkin's disease patients, especially those with involvement of lower abdominal nodes (III2B), extensive pulmonary disease, or mixed cellularity histology. Radiation therapy or additional chemotherapy courses are required for these patients.     

An evaluation of total nodal irradiation as treatment for stage III A Hodgkin's disease.

Between April 1969 and December 1974, 37 patients with surgically staged III A Hodgkin's disease were treated with total nodal irradiation (TNI). Their probability of relapse-free survival at 7 years is 51% and overall survival 82% with the majority of patients remaining disease free after retreatment with MOPP (10 of 16). In contrast, 21 stage III B patients treated with TNI and MOPP chemotherapy over the same time period have a relapse-free survival of 74% and overall survival of 91%. Because of superior results in treating stage III B patients with combined modality treatment, we fell that a relapse-free survival of 51% may not justify continuation of TNI as the only modality of treatment for patients with stage III A disease, and we have initiated a trial of combined radiation therapy and MOPP chemotherapy in these patients. The most effective treatment of stage III A Hodgkin's disease, however, remains uncertain and depends both on the ultimate risk of combined modality treatment and the success of retreatment following relapse after radiation.     

Concomitant 5-fluorouracil infusion, mitomycin C and radical radiation therapy in esophageal squamous cell carcinoma

This is a retrospective comparison of patients with unresected esophageal squamous cell carcinoma treated by radiation therapy and chemotherapy (21 patients) versus radiation therapy alone (34 patients). Pretreatment characteristics were comparable in both groups. In the combined modality group, treatment was given in split courses with concomitant radiation therapy (20 to 25 Gy in 10 fractions on days 1-12 and days 42-54) and chemotherapy (bolus Mitomycin C on day 1; 96 hr. of continuous 5 Fluorouracil infusion on days 1-4 and days 42-46). There was improvement in local disease control with the combined modality approach. Initial complete response was achieved in 86% of the radiation and chemotherapy group, versus 57% of the radiation alone group. The one-year local relapse-free rate was 67% versus 35%, and 2 year rate was 41% versus 28%. (p less than 0.05). The 1-year and 2-year survival was 64% and 32% respectively, for the radiation and chemotherapy group, versus 28% and 10% respectively for the radiation alone group (p less than 0.05). The majority of patients had disease relapsed, 81% of the combined modality group and 97% of the radiation alone group. However, the pattern of failure was different in the two groups. In the radiation and chemotherapy group, 29% had local failure alone, 53% had distant failure alone, and 18% had both local and distant failure. In the radiation alone group, 33% had local failure alone, 24% had distant failure alone, and 43% had both local and distant failure. Concomitant radiation therapy, 5 Fluorouracil infusion and bolus Mitomycin C is effective treatment for local control in esophageal squamous cell carcinoma, but not for distant hematogenous metastases. This combined modality treatment was well tolerated, with little additional hematological toxicity, esophagitis and stomatitis over radiation therapy alone.     

Locally advanced (noninflammatory) carcinoma of the breast: results and comparison of various treatment modalities

From 1968-1987 237 women with Stage III, noninflammatory breast cancer were treated with various modalities. Ninety-three (39%) had Stage IIIA tumors, and 144 (61%) had Stage IIIB, noninflammatory tumors (AJC, 1983 staging). Median follow-up was 5.4 years (range 2 to 22 years). No patients were lost to follow-up. Thirty-five patients (15%) were treated with irradiation alone, 27 (11%) with irradiation and adjuvant systemic therapy, 80 (34%) with mastectomy and irradiation, and 95 (40%) with combined mastectomy, irradiation, and systemic therapy. Local/regional control by treatment at 5 and 10 years, respectively, was 31% and 31% for irradiation alone, 47% and 47% for irradiation and systemic therapy, 80% and 80% for irradiation and mastectomy, and 93% and 78% for irradiation, mastectomy, and systemic therapy (p less than .0001). Actuarial disease-free survival by treatment was 19% and 12% for irradiation alone, 25% and 18% for irradiation and systemic therapy, 34% and 20% for irradiation and mastectomy, and 41% and 31% for irradiation, mastectomy, and systemic therapy, at 5 and 10 years, respectively (p = .0001). Patients given systemic therapy and/or irradiation prior to mastectomy had a better local/regional control and DFS and actuarial survival, although not achieving statistical significance (p = 0.10). Of the triple modality group of patients, there were no chest wall failures with chest wall doses greater than 5040 cGy (p = 0.3). There were 40/237 (17%) grade 2 or greater treatment sequelae. The administration of chemotherapy significantly increased complications.     

Stage III Hodgkin's disease: improved survival with combined modality therapy as compared with radiation therapy alone

This is a retrospective analysis of 120 patients with pathologically stage IIIA and IIIB Hodgkin's disease treated from April 1969 to December 1982. The median follow-up was 108 months. Treatment consisted of radiation therapy (RT) alone in 54 patients and combined radiation therapy and MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) chemotherapy (CMT) in 66 patients. Stage III patients treated with CMT have an improved actuarial 12-year survival as compared with patients treated with RT alone with MOPP reserved for relapse (80% v 64%; P = .026). The 12-year actuarial freedom from first relapse by treatment for stage III patients is 83% and 40%, respectively (P less than .0001). Improved survivals following combined modality therapy are seen for the following subgroups of stage III patients: stage III2, 66% (CMT) v 44% (total nodal irradiation; TNI), P = .04; stage III1, 97% (CMT) v 73% (TNI), P = .05; stage III mixed cellularity or lymphocyte depletion histology, 94% (CMT) v 65% (TNI), P = .007; and stage III extensive splenic involvement, 77% (CMT) v 58% (TNI), P = .02. These survival differences are not seen in patients with nodular sclerosis or lymphocyte predominance histology or in patients with minimal splenic involvement. These data indicate that the initial use of CMT in stage III Hodgkin's disease results in an improved survival as compared with initial treatment with RT with MOPP reserved for relapse. Patients with limited Stage IIIA disease may still be candidates for radiation therapy alone.     

N2 (clinical) non-small cell carcinoma of the lung: prospective trials of radiation therapy with total doses 60 Gy by the Radiation Therapy Oncology Group.

Clinical Stage III (N2) non-small cell carcinoma of the lung encompasses a large group of patients, frequently treated with radiation therapy alone, who are now considered to have borderline-resectable tumors. Pilot studies are proceeding which use combinations of resection, radiation therapy, and chemotherapy. To place trials of combination therapy in perspective with contemporary results of radiation therapy alone, recently completed trials of the RTOG were analyzed specifically for clinical Stages T1-3N2. A prospective randomized trial of hyperfractionated radiation therapy (HFX), conducted from 1983 through 1987, compared total doses of 60.0, 64.8, and 69.6 Gy using 1.2 Gy bid with greater than or equal to 4 hr interval. After acute and late effects were considered tolerable, 74.4 Gy and 79.2 Gy arms supplanted the two lowest dose arms. Survival was compared among the five total dose arms, and with 60 Gy in 30 fractions in 6 weeks (standard fractionation-STD) from earlier RTOG studies. Of 516 HFX patients analyzed, 296 (57.3%) with Performance Status (PS) 70-100 and less than 5% weight loss (favorable) had a significantly (p = .001) better survival than those with PS 50-69 or weight loss greater than 5%. Patients with RTOG Stage III (361, 70.0%) experienced better survival (p = .027) than RTOG Stage IV M0. The 69.6 Gy total dose arm was significantly (p = .031) better in favorable RTOG Stage III patients than all other total dose arms: the 1-year survival rate was 58% and the 3-year rate was 20%. The 69.6 Gy HFX results were significantly (p = .002) better than results with STD fractionation in comparable patients from earlier RTOG trials (1-year survival = 30%, 3-year survival = 7%). A prospective, randomized Phase III comparison of STD with 60 Gy versus HFX with 69.6 Gy is underway. These results provide benchmarks for studies of surgical resection combined with chemotherapy and/or radiation therapy until results of prospective comparisons with concurrent controls are available.     

Stage III follicular lymphoma: long-term follow-up and patterns of failure

PURPOSE: To analyze the long-term outcomes and pattern of failures for Stage III follicular lymphomas. METHODS AND MATERIALS: A retrospective review of all patients with Stage III follicular lymphoma presented to our institution between 1978 and 1993 was performed. One hundred ten patients were eligible and form the basis of this analysis. Fifty-seven patients were male. The median age was 57 years (range: 21-82 years). The treatments were as follows: chemotherapy alone (CTX), 39 patients; combined modality with chemotherapy and radiation therapy (CMT), 69; radiation therapy alone, 2. Radiation therapy fields were as follows: regional, 13 patients; extended, 6; subtotal, 44; and central lymphatic, 8. The median number of chemotherapy cycles was 8, and 98 patients received doxorubicin-containing regimens. Enough information was available to calculate the International Prognostic Index for 107 patients. The following prognostic factors were examined for predictive value in overall survival (OS) and freedom from progression (FFP) by univariate and multivariate analyses: International Prognostic Index, gender, lactate dehydrogenase (LDH) (normal vs. elevated), B symptoms, performance status, beta-2 microglobulin, presence or absence of a bulky disease, age (60 years), number of sites of involvement, treatment (CTX vs. CMT), and pathology. To minimize patient selection biases given the nature of the retrospective analysis, the patterns of relapse were analyzed only for the patients who achieved a complete response. RESULTS: The median follow-up for the alive patients was 9.5 years (range: 1.1-19.5 years). Complete response was achieved in 80 patients: 24 of 39 patients in the CTX group (62%), 54 of 69 patients in the CMT group (78%), and 2 of 2 patients in the radiation therapy alone group. The actuarial 5- and 10-year OS rates were 65% and 42%, respectively. The 5- and 10-year FFP was 42% and 26%, respectively. Significant prognostic factors by multivariate analyses were age and LDH for OS and LDH for FFP. For complete responders, 5-year freedom from recurrence in the original sites of involvement (with or without recurrence in the new sites) was 43% for CTX and 60% for CMT patients (p = 0.03, Wilcoxon). Five-year freedom from isolated recurrence in the original sites of involvement was 60% for CTX and 69% for CMT patients (p = 0.17). The 5-year overall FFP was 43% for CTX patients and 56% for CMT patients (p = 0.06). CONCLUSION: Combined modality treatment seems to give an advantage in terms of disease control in the primary sites compared to chemotherapy alone, though the advantages in OS and FFP were not statistically significant in our patient population. By multivariate analyses, LDH was a significant prognostic indicator for OS and FFP, whereas age was for OS.     

Substaging of stage III Hodgkin's disease

Patients with stage III Hodgkin's disease require a staging laparotomy to accurately define two main subgroups of patients, III1 and III2. Selection of treatment modality for each group is very important. The majority of patients with pathological stage III Hodgkin's disease are treated with combined modality therapy; however, a subset of patients can be effectively treated with radiation therapy alone.     

Radiation therapy for nasopharyngeal carcinoma. Retrospective review of 105 patients based on a survey of Kansai Cancer Therapist Group

One hundred five patients with nasopharyngeal carcinoma were treated with radiation therapy combined with or without chemotherapy at 16 of the participating institutes in Kansai Cancer Therapist Group, Japan, from January 1978 to December 1980. The study comprised 77 males and 28 females; their ages ranged from 15 to 80 years (mean, 53 years). Five-year survival rates according to stage were as follows: Stage I, 100%; Stage II, 67%; Stage III, 44%; and Stage IV, 34%. As far as Stage IV disease was concerned, the radiation therapy only group showed significantly poorer prognosis than the combined radiation and chemotherapy group (P less than 0.05). Concerning the N stage and treatment method, the radiation therapy only group showed a higher metastatic rate than the chemotherapy combined group (35% versus 14%, P less than 0.05).     

Outcomes of patients receiving radiation for carcinoma of the rectum. Results of the 1988-1989 patterns of care study

BACKGROUND: Clinical trials of surgical adjuvant treatment for patients with rectal carcinoma (RC) indicate that postoperative radiation therapy with concurrent chemotherapy (CRT) is superior to postoperative radiation alone (RT) or surgery alone. Whether preoperative treatment is superior to postoperative treatment is controversial. This Patterns of Care Study (PCS) surveyed patients with RC treated with radiation during the years 1988-1989 to determine the national practice standards and outcomes and to compare these results with those of clinical trials. METHODS: A national survey of 73 institutions was conducted using 2-stage cluster sampling, and specific information on 406 patients with RC who received radiation at 69 facilities was collected. Follow-up information on 215 patients was subsequently collected by mail survey. There were no significant differences between the known prognostic indicators or treatment-related variables for patients for whom follow-up was available compared with the variables for patients for whom follow-up was not available. Follow-up ranged from 0 to 8.44 years with a median of 4 years. One hundred fifty-four patients (71%) received postoperative treatment, either RT (37%) or CRT (34%); and 40 (18%) received preoperative treatment, either RT (15%) or CRT (3%). Ninety-six patients (45%) received chemotherapy, and for 86% of those patients chemotherapy was administered concurrently with radiation. RESULTS: Survival was stage-dependent (85% Stage I, 69% Stage II, and 54% Stage III at 5 years, P = 0.04). Survival was also substage-dependent, and patients with C(1) cancer had significantly higher 5-year survival than those with C(2)/C(3) cancer (89% vs. 48%, P = 0.008). Local failure was similar for Stage II and Stage III patients (10% vs. 11% at 5 years, respectively). In multivariate analyses, only stage and use of chemotherapy were significant to survival (Stage III vs. Stage I and II, relative risk [RR] = 2.52, and chemotherapy vs. no chemotherapy, RR = 0.46). A significantly higher 5-year survival rate was seen with postoperative CRT than with postoperative RT (69% vs. 50%, P = 0. 011). Preoperative radiation resulted in a significantly higher 5-year survival rate than postoperative radiation (85% vs. 50%, P = 0.0006), but not compared with postoperative CRT. Survival and local failure did not differ according to radiation therapy interruption or the interval between surgery and radiation. CONCLUSIONS: Stage is an important prognostic indicator for survival, and among patients with Stage III malignancies survival in the substage C(1) is significantly higher than in the substages C(2) and C(3). As has been demonstrated in randomized trials, adjuvant postoperative CRT is superior to postoperative RT for patients with RC in this national study. These nationwide results of adjuvant treatment are comparable to those reported in randomized trials. The use of CRT was the only treatment-related factor that resulted in a significant reduction in the risk of death.     

Primary bone lymphoma: treatment results and prognostic factors with long-term follow-up of 82 patients

BACKGROUND: To the authors' knowledge, there is limited information on the preferred treatment and long-term prognosis of primary bone lymphomas (PBLs). All PBL cases treated at the study center between 1963 and 2003 were analyzed to determine patient, disease, and treatment factors that could affect outcome measured by overall survival (OS), cause-specific survival (CSS), and freedom-from-treatment failure (FFTF). METHODS: A total of 101 patients with PBL diagnosed at the study institution were identified. Nineteen patients were excluded because they transferred their treatment or follow-up to another center. Disease control, survival, and prognostic factors were analyzed for all 82 remaining patients. RESULTS: The median age of the patients was 48 years (range, 11-83 years). Approximately 80% presented with diffuse large-cell lymphoma (DLCL), and 81% presented with Ann Arbor Stage I or II disease. Approximately 57% were treated with combined modality therapy, 14% were treated with radiation therapy alone, and 30% were treated with chemotherapy alone. The median follow-up was 67 months (range, 2-280 months). The 5-year OS, CSS, and FFTF were 88%, 96%, and 81%, respectively. The 5-year OS for patients treated with combined modality versus single-modality therapy was 95% versus 78% (P = .013), and the 5-year FFTF for patients treated with combined modality versus single-modality therapy was 90% versus 67% (P = .025). The 5-year CSS for patients treated with combined modality versus single-modality therapy was 95% versus 83% (P = .065). Using a Cox regression for multivariate analysis, age < 40 years and use of combined modality therapy were found to be favorable prognostic factors for OS, CSS, and FFTF. CONCLUSIONS: To the authors' knowledge, the current study is the largest series of patients with PBL treated with modern curative modalities. The data demonstrate that primary lymphoma involving the bone has an excellent prognosis. Patients with PBL treated with combined modality versus single modality therapy were found to have a superior outcome, with a significantly better survival.     

Premenopausal breast cancer patients treated with conservative surgery, radiotherapy and adjuvant chemotherapy have a low risk of local failure

The use of adjuvant chemotherapy in premenopausal breast cancer patients with positive nodes is now routine, but the optimal local treatment of these patients is uncertain. To determine the effect of adjuvant chemotherapy on the likelihood of local recurrence as the first site of failure in premenopausal patients treated with conservative surgery (CS) and radiotherapy (RT), we examined the outcome of 74 patients treated with CS, RT, and adjuvant chemotherapy and compared it to the outcome in 192 patients treated with CS and RT alone. Adjuvant chemotherapy consisted of four or more cycles of either a doxorubicin-containing regimen or cyclophosphamide, methotrexate, and 5-fluorouracil. All patients were less than 50 years old, had UICC-AJCC Stage I or II breast cancer treated between 1968 and 1981, had gross excision of the primary tumor, and had a total radiation dose to the primary tumor bed of greater than or equal to 6000 cGy. Factors predicting for local recurrence, such as extensive intraductal carcinoma and age less than 35, were equivalent in the two groups. Women treated with adjuvant chemotherapy had significantly worse T- and N-stages than women treated with conservative surgery and radiotherapy alone: 61% versus 36% had T2 tumors (p = 0.0003), 34% versus 6% had clinically positive nodes (p less than 0.0001), and 97% versus 4% had pathologically positive nodes (p less than 0.0001). Despite the poorer prognosis of patients treated with adjuvant chemotherapy, within 5 years of diagnosis, 4% of patients who received adjuvant chemotherapy had their initial relapse in the breast and 24% had initial failure elsewhere, compared with 15% local failure first and 14% failure elsewhere first for those treated without chemotherapy (p = 0.01). We conclude that premenopausal patients with positive nodes treated with combined modality therapy (conservative surgery, radiation therapy, and adjuvant chemotherapy) have a low risk of local recurrence as a first site of failure. These results suggest a possible interaction between radiation therapy and chemotherapy in their effects on local tumor control.     

Stage Ia Non-Hodgkin's Lymphoma of the Waldeyer's Ring Limited chemotherapy and radiation therapy versus radiation therapy alone

Seventeen patients with stage IA non-Hodgkin's lymphoma of the Waldeyer's ring were treated with radiation therapy with or without chemotherapy. All lesions were judged as having intermediate grade malignancy in the Working Formulation. Eight patients received combined treatment with three cycles of cyclophosphamide, doxorubicin, vincristine and prednison (CHOP) and radiation therapy with 30 to 40 Gy. Another 9 patients were treated with radiation therapy 40 to 60 Gy alone. After a median follow-up of 69 months, all 8 patients, treated with combined modality were alive and relapse-free, whereas 4 of the 9 treated with irradiation alone had relapsed. All relapses occurred transdiaphragmatically. Two of the 4 relapsing patients were saved, but the other two died of the disease. the 5-year relapse-free and cause-specific survival rates were 100% and 100% in the combined modality group, and 56% and 76% in the radiation therapy alone group (relapse-free: p = 0.04, cause-specific: p = 0.16). There were no serious complications related to treatment, although most patients complained of mouth dryness and most patients given CHOP had paresthesia. Our opinion was that the total impact of these two side-effects on quality of life was less pronounced after combined modality than after radiation therapy alone. Limited chemotherapy and radiation therapy seemed to be more beneficial than radiation therapy alone not only in relapse-free survival but also in quality of life after treatment.     

Radiation therapy for carcinoma of the cervix with biopsy-proven positive para-aortic lymph nodes

Purpose: To evaluate local tumor control, cause-specific survival, patterns of relapse, and toxicity in patients with cervical cancer and positive para-aortic lymph nodes treated with radiation therapy alone.Methods: This is a retrospective chart review of 43 patients with cervical cancer and biopsy-proven positive para-aortic lymph nodes treated with radiation therapy treated from 1965 to 1993. There were 15 patients with clinical Stage I disease, 12 with Stage II, and 16 with Stage III. Patients were treated with external irradiation to the pelvis and para-aortic regions combined with brachytherapy. None received chemotherapy.Results: The 5-year overall survival rate was 32% and the median overall survival was 2.2 years. The 5-year cause-specific survival rate was 49% and the median cause-specific survival was 2.7 years. The cause-specific survivals at 5 years were 47% for Stage I, 64% for Stage II, and 46% for Stage III. Tumor recurrence occurred in 20 patients. The sites of recurrence were in the pelvis only in 3, the pelvis and distant metastasis in 9, and distant metastasis only in 8 patients. Severe, grade 3 complications occurred in 2 patients. One patient developed an enterovaginal fistulas and 1 developed radiation myelitis.Conclusion: Pelvic and para-aortic irradiation and brachytherapy resulted in a 49%, 5-year, cause-specific survival. Clinical tumor stage did not effect outcome. The majority of relapses occurred at distant sites. Toxicity was acceptable. Systemic chemotherapy should be considered as adjunctive therapy for these patients.     

Long-term results of combined modality treatment with I-125 implantation for carcinoma of the pancreas.

From 1981 to 1987, 81 patients with localized, unresectable carcinoma of the pancreas were treated at Thomas Jefferson University Hospital with a combination of intraoperative Iodine-125 implantation, external beam radiation, and peri-operative systemic chemotherapy. Fifty patients had Stage II disease and 31 patients had Stage III disease. Radioactive Iodine-125 seeds were implanted intraoperatively into the tumor to deliver a minimum peripheral dose of 12,000 cGy over one year. This was followed by external beam radiation (50-55 Gy) and systemic chemotherapy (5-FU, Mitomycin-C +/- CCNU). Incidence of peri-operative mortality was 5% (4/81). Early morbidity was observed in 34% of patients and late complications in 32%. A median survival of 12 months and 2- and 5-year survival rates of 21% and 7% were observed. The determinate 2- and 5-year survival rates were 28% and 13%, respectively. The overall 2- and 5-year survival rates with Stage II disease were 27% and 8% and for Stage III disease, 13% and 3%, respectively (p less than 0.05). The determinate 2- and 5-year survival rates were 34% and 19% for Stage II and 19% and 5% for Stage III disease, respectively (p = 0.08). Local control of disease was achieved in 71% of patients. This combined modality approach appears to have achieved satisfactory local control of primary cancer and long term survival of selected patients.     

The importance of brachytherapy technique in the management of primary carcinoma of the vagina.

This retrospective analysis of 49 cases of primary carcinoma of the vagina treated with radiation therapy alone from 1970-1988 examines the results of treatment with an emphasis on the importance of brachytherapy technique. Thirty-six patients were treated with combined external beam radiation and brachytherapy, 11 patients were treated with external beam alone, and two patients were treated with brachytherapy alone. Brachytherapy techniques used included intracavitary implants, temporary Ir-192 interstitial implants, and permanent I-125 interstitial implants. Intracavitary therapy included the use of a fractionated high dose rate intravaginal cylinder, tandem and ovoids, and a low dose rate intravaginal cylinder. The 5-year actuarial survival was 44% for Stage I (six patients), 48% for Stage II (27 patients), 40% for Stage III (10 patients), and 0% for Stage IVa and IVb (six patients). There was a significant increase in the 5-year actuarial survival for those patients who had brachytherapy as part of their treatment compared to those patients treated with external beam alone (50% vs. 9%) (p < .001). For Stages II and III, there was a trend toward improved actuarial and crude disease free survival with the use of a temporary Ir-192 interstitial implant as part of the treatment compared to the use of intracavitary brachytherapy as part of the treatment (80% vs. 45%) (p = 0.25) and (75% vs. 44%) (p = 0.08), respectively. Brachytherapy plays an important role in the management of primary vaginal cancer. A temporary interstitial implant should be used over an intracavitary form of therapy for more invasive disease.     

Combined chemoradiation for the management of nasal natural killer (NK)/T-cell lymphoma: elucidating the significance of systemic chemotherapy

The objective of this analysis was to evaluate the efficacy and treatment outcome of CHOP and CHOP combined with nitrosourea chemotherapy in natural killer (NK)/T-cell lymphoma of the nasal cavity. Sixty-three patients with NK/T-cell lymphoma of the nasal cavity were treated with CHOP or CHOP combined with oral nitrosourea chemotherapy between January 1997 and June 2005. By the Ann Arbor Lymphoma Staging Classification, 57 patients (90%) had Stage IE or IIE disease and six patients (10%) had Stage III or IV disease. All patients with Stage IE or IIE disease were intended to be treated curatively with combined chemoradiation; and patients who had Stage III or IV disease were treated with chemotherapy alone with curative intention. Chemotherapy consisted of: (1) up to six cycles of the standard CHOP based regimen, or (2) up to six cycles of the standard CHOP based regimen with oral Semustine dosed at 120 mg (or Lomustine dosed at 100mg) on day 1 of each chemotherapy cycle. External beam radiation therapy was delivered by daily conventional fractionation by Co-60 or 6MVx linear accelerator for patients with Stage IE or IIE disease. The radiation dose to the tumor bed was between 36 and 50 Gy with a median dose of 45 Gy. Fifty-three patients received chemotherapy prior to radiation, and four patients were treated with involved field radiation before chemotherapy. The median follow up for all 44 surviving patients was 31 months (range: 6-104 months). The 2-year progression-free survival (PFS) and overall survival (OS) rates were 60% and 70%, respectively. The PFS and OS of patients who were treated with or without oral nitrosourea in addition to CHOP were 73% vs. 44% (P=0.035) and 75% vs. 64% (P=0.276), respectively. Nine patients with Stage IE or IIE diseases developed disease progression during their planned treatment and died within 10 months after the initiation of treatment; Six patients who achieved complete response (CR) after planned chemoradiation developed systemic recurrence and died at 13-48 months despite salvage treatment; one patient died of Hemophagocytic Syndrome during radiotherapy after achieving CR from chemotherapy. Three patients with Stage III or IV disease died during chemotherapy or during salvage treatment at 2, 4, and 19 months, respectively. Among the 59 patients who received chemotherapy as their initial treatment, 29, 6, 12, and 12 patients had complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) respectively after chemotherapy. The 2-year overall survival rates for these four groups of patients were 100%, 75%, 60%, and 17%, respectively (P<0.0001). Multivariate analysis revealed that International Prognostic Index (IPI) for Lymphoma, perforation of nasal septum as a presenting symptom, "B" symptoms, ECOG performance, as well as response after chemotherapy, were significant independent prognostic factors for this group of patients. The extent of response after induction chemotherapy is significantly related to the treatment outcome of patients with nasal NK/T-cell lymphoma. CHOP based chemotherapy combined with oral nitrosourea followed by involved field radiotherapy may provide improved treatment results compared to conventional CHOP chemotherapy and radiation. This strategy needs to be optimized and tested in a prospective trial for its efficacy.     

Treatment of advanced-stage massive mediastinal Hodgkin's disease: the case for combined modality treatment

In the initial series of 198 patients treated at the National Cancer Institute (NCI) with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy for Hodgkin's disease, a review of presenting chest radiographs available on 192 of these patients showed 49 patients with mediastinal masses greater than one third the greatest posteroanterior chest diameter. Five patients had stage IIB disease, and 44 had stage III or IV disease. Thirty-five (71%) patients achieved a complete remission with MOPP chemotherapy. Fourteen (40%) of the complete responders relapsed, but four of these achieved durable remissions in response to subsequent therapy. Thirty (61%) patients have died (14 induction failures, nine relapsed patients, seven complete responders in remission). Thus, with a median follow-up of 20 years (range, 15 to 23), the overall survival for the group is 39%, and the disease-free survival for the complete responders is 60%. A subset of 10 patients received mantle radiation therapy after maximal response to MOPP. One of these patients failed to achieve complete remission, but among the nine complete responders only one has relapsed. In contrast, 13 of 26 (50%) patients achieving a complete response to MOPP alone have relapsed (P2 = .0536). Although MOPP alone was not prospectively compared with MOPP plus radiation therapy in the treatment of advanced-stage massive mediastinal Hodgkin's disease in this series, the retrospective analysis shows a nearly significant difference in disease-free survival favoring combined modality treatment. The difference in tumor mortality between MOPP-treated (44%) and combined modality-treated patients (80%) was also nearly significant (P2 = .055). However, overall survival differences between patients treated with MOPP alone and those treated with combined modality therapy were not significantly different (P2 = 0.23) because of the mortality related to late complications of combined modality treatment.     

Treatment selection for stage IIIA Hodgkin's disease patients

Two treatment policies for the therapy of patients with Stage IIIA Hodgkin's disease are compared. From 1969-1976, 49 newly diagnosed and pathologically staged IIIA patients received total nodal irradiation (TNI) alone (no liver irradiation). Although actuarial survival was 80% at 5 years and 68% at 10 years, actuarial freedom from relapse was only 38% at 5 years. Accordingly, a new treatment policy was instituted in 1976. Patients with either CS IIIA disease, multiple splenic nodules, IIIA with a large mediastinal mass or III2, received combined modality therapy (combination chemotherapy and irradiation). All others received TNI. Thirty-six patients have been treated under the new program. The actuarial survival is 90% at 5 years and the relapse-free survival is 87%, suggesting the superiority of this approach.