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.     

Stage IA-IIB Hodgkin's disease: staging and treatment of patients with large mediastinal adenopathy

Ninety-two patients with clinically staged (CS) IA-IIB Hodgkin's disease (HD) with large mediastinal adenopathy (LMA) underwent three different staging and treatment approaches between April 1969 and December 1984. These approaches included: (1) staging laparotomy followed by radiation therapy (RT) alone; (2) staging laparotomy followed by combined RT and chemotherapy (CMT); or (3) clinical staging followed by CMT. Patients treated with CMT were more likely to have "B" symptoms, extension into extranodal sites, or stage III disease. Patients treated with RT alone had a significantly higher risk of relapse as compared to patients receiving CMT. No overall survival differences were seen between the three groups of patients. For patients treated with CMT without RT to the spleen or abdominal nodes, the risk of relapse in the abdomen was low (4%). These data suggest that for those CS I-II HD patients with LMA who are treated with CMT, the role for staging laparotomy and abdominal irradiation is limited. RT alone remains an option for some patients with LMA, but careful assessment of the anatomic extent of thoracic disease as well as staging laparotomy is essential if such treatment is recommended.     

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.     

The impact of pelvic recurrence and elective pelvic irradiation on survival and treatment morbidity in early-stage Hodgkin's disease

A retrospective analysis of patients with supradiaphragmatic Stage I-II Hodgkin's disease was performed to assess the impact of pelvic recurrence and elective pelvic irradiation on survival and treatment morbidity. One hundred twenty patients were treated with radiotherapy (RT) alone; 38 received total nodal (including pelvic) irradiation (TNI), 63 received modified total nodal (excluding pelvic) irradiation (MTNI), and 19 received involved-field or mantle irradiation only (less than MTNI). Thirty-three patients received combined-modality therapy. In laparotomy-staged (PS) patients treated with RT alone, the overall treatment failure rate was 13% after TNI, 24% after MTNI, and 43% after less than MTNI. The pelvic failure rate in PS patients was 0% after TNI, 9% after MTNI, and 29% after less than MTNI. Cause-specific deaths in patients treated with RT alone occurred in 10% following less than MTNI, 13% following MTNI, and 10% following TNI. Cause-specific deaths due to pelvic failure in patients treated with RT alone occurred in 5% following IF and 6% following MTNI, and also occurred in 7% of patients receiving combined-modality therapy. The potential disadvantages of elective pelvic irradiation in early-stage Hodgkin's disease include compromise of future tolerance of chemotherapy in the event of treatment failure, and infertility. Gonadal function was assessed in 67 patients less than 35 years old at the time of treatment. Compromise of gonadal function was correlated with the lack of special testicular shielding during pelvic irradiation and chemotherapy in the male, and with no oophoropexy before pelvic irradiation in the female. Twelve of 26 patients with recurrence after either less than MTNI or MTNI, with or without chemotherapy, were alive and without evidence of disease at greater than 2 years after completing salvage therapy, compared with 7 of 11 patients with recurrence after TNI.     

Low-dose radiation therapy and reduced chemotherapy in childhood Hodgkin's disease: the experience of the French Society of Pediatric Oncology.

PURPOSE: With the aim of decreasing undesirable side effects of therapy, we investigated the reduction of both chemotherapy and radiation therapy (RT) in children with Hodgkin's disease, and compared Adriamycin (doxorubicin; Farmitalia Carlo Erba, Rueil-Malmaison, France), bleomycin, vinblastine, and dacarbazine (ABVD) alone to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and ABVD in favorable cases and assessed the effectiveness of low-dose RT (20 Gy) after good response to chemotherapy. PATIENTS AND METHODS: A French national study began in 1982 that included 238 pediatric patients with Hodgkin's disease. Initial staging was clinical and without laparotomy. In patients with localized disease (IA-IIA), an equivalence trial compared the effectiveness of four cycles of ABVD with two cycles of ABVD that were alternated with two cycles of MOPP. Patients with more advanced disease (IB-IIB-III-IV) received three courses of MOPP that was alternated with three courses of ABVD. All of the patients who achieved a good remission after chemotherapy were administered 20 Gy RT, which was limited to the initially involved areas for localized disease, and encompassed the paraaortic nodes and the spleen as well for more advanced stages. When a good remission was not obtained, 40 Gy RT was administered. RESULTS: At the completion of chemotherapy, 227 patients (97%) were considered good responders, whereas 11 did not achieve a good remission. With a median follow-up of 6 years, the 6-year actuarial survival was 92% and the disease-free survival was 86%. The relapse-free survival in favorable stages was 90% in the ABVD arm and was 87% in the MOPP and ABVD arm. In June 1987, inclusion of stage IV patients was discontinued because of poor results. CONCLUSIONS: Present findings indicate that (1) in favorable stages, ABVD alone and alternating MOPP and ABVD are equivalent, and (2) chemotherapy followed by 20 Gy RT represents a valid therapeutic approach in the vast majority of children with Hodgkin's disease.     

Increased risk of secondary acute nonlymphocytic leukemia after extended-field radiation therapy combined with MOPP chemotherapy for Hodgkin's disease

The purpose of this study was to evaluate the influence of the number of mechlorethamine, vincristine, procarbazine, and prednisolone (MOPP) cycles and the extent of irradiation on the risk of secondary acute nonlymphocytic leukemia (SANLL) after a single combined treatment for Hodgkin's disease (HD). Between April 1972 and May 1980, 462 patients with HD clinical stage (CS) I, II, and III were prospectively treated with three or six cycles of MOPP and supra- and/or infradiaphragmatic irradiation (40 Gy). Four hundred forty-one patients achieved complete remission (CR). By January 1988, 237 patients had been followed-up in first CR for at least 10 years. Ten patients developed SANLL between the 34th and 123rd month of CR. The 15-year SANLL risk is 3.5% +/- 2.7%. Cox's stepwise regression analysis performed with all initial and treatment covariates (sex, age, histology, splenectomy, MOPP chemotherapy, and irradiation extent) showed that the only significant explanatory variable of SANLL risk was the irradiation extent (P less than .002). Using the log-rank test, SANLL risk ranged from 2.2% for supradiaphragmatic irradiation alone to 9.1% for subtotal (STNI) or total nodal irradiation (TNI) (P less than .001). These results strongly suggest that extended high-dose irradiation and MOPP chemotherapy should not be combined for the treatment of HD.     

Thoracic irradiation in Hodgkin's disease: disease control and long-term complications

A total of 590 patients with Stage IA-IIIB Hodgkin's disease received mantle irradiation at the Joint Center for Radiation Therapy between April 1969 and December 1984 as part of their initial treatment. Recurrence patterns as well as pulmonary, cardiac and thyroid complications were analyzed. Pulmonary recurrence was more frequently seen in patients with large mediastinal adenopathy (LMA); 11% of patients with LMA recurred in the lung in contrast to 3.1% with small or no mediastinal disease, p = 0.003. Hilar involvement, when corrected for size of mediastinal involvement, was not predictive of lung relapse. Patients with LMA also had a high rate of nodal relapse above the diaphragm (40%) following radiation therapy (RT) alone as compared to similarly treated patients with small or no mediastinal adenopathy (6.5%), p less than 0.0001. This risk of nodal recurrence was greatly reduced (4.7%) for LMA patients receiving combined radiation therapy and chemotherapy (CMT), p less than 0.0001. Sixty-seven patients (11%) with hilar or large mediastinal involvement received prophylactic, low dose, whole lung irradiation. No decrease in the frequency of lung recurrence was seen with the use of whole lung irradiation. Radiation pneumonitis was seen in 3% of patients receiving radiation therapy alone. In contrast, the use of whole lung irradiation was associated with a 15% risk of pneumonitis, p = 0.006. The risk of pneumonitis was also significantly increased with the use of chemotherapy (11%), p = 0.0001. Cardiac complications were uncommon with pericarditis being the most common complication (2.2%). Thyroid dysfunction was seen in 25% of patients and appeared to be age-related. These data suggest that the long-term complications of mantle irradiation are uncommon with the use of modern radiotherapeutic techniques. The use of prophylactic whole lung irradiation is no longer recommended since its use did not reduce pulmonary relapse but did increase the risk of pneumonitis. Chemotherapy is also associated with an increased risk of pneumonitis, however, its use in patients with large mediastinal adenopathy appears justified.     

Radiation dose selection in Hodgkin's disease patients with large mediastinal adenopathy treated with combined modality therapy

PURPOSE: To determine the effective dose of consolidation radiation in Hodgkin's disease (HD) patients with large mediastinal adenopathy (LMA) treated with combined modality therapy (CMT). METHODS AND MATERIALS: Eighty-three HD patients with LMA receiving CMT between 1983 and 1997 at Duke University and Yale University were identified. Patients underwent complete clinical staging. The staging breakdown was: IA, 4 patients; IB, 1 patient; IIA, 25 patients; IIB, 33 patients; IIIA, 3 patients; IIIB-6 patients; IVA, 2 patients; and IVB, 9 patients. All patients received induction chemotherapy (CT) as follows: MOPP/ABV(D), 31 patients; BCVPP, 15 patients; ABVD, 24 patients; MOPP, 3 patients; and other regimens, 10 patients. Following 6 cycles of CT, patients were restaged and classified as having either complete response (CR) or induction failure (IF). Post-CT gallium scans were obtained in 52 patients. Patients with residual radiographic abnormalities were classified as having CR if they were gallium-negative and clinically well otherwise. Following induction CT, 78 patients had a CR. There were 5 IFs. Consolidation irradiation was administered to all sites of initial involvement in patients who had achieved CR. RT dose varied. Patients were grouped into the following dose ranges: < or = 20 Gy, 12 patients; 20-25 Gy, 24 patients; 25-30 Gy, 30 patients; > or = 30 Gy, 12 patients. RESULTS: Overall survival and failure-free survival were both 76% at 10 years. Of the 78 CR patients, 15 failed. Patterns of failure were in-field alone, 8 patients; out of field alone, 2 patients; and combined, 5 patients. Failure patterns by RT dose were: < or = 20 Gy, 0/12; 20-25 Gy, 7/24; 25-30 Gy, 5/30; > or = 30 Gy, 3/11. There was no apparent correlation between RT dose and subsequent failure. Post chemotherapy gallium scans were helpful in predicting for failure. Of 48 patients in whom the gallium was negative after chemotherapy, there were 6 failures, compared with 9 failures among 30 patients in whom gallium was not done after chemotherapy (p = 0.066). Additionally, patients receiving adriamycin-based chemotherapy regimens had improved outcomes compared to those not receiving adriamycin (p = 0.03.) CONCLUSIONS: These retrospective data suggest that low-dose radiotherapy following CR achieved with induction chemotherapy (particularly when documented with gallium scanning) may be as effective as higher doses for bulky HD at presentation. Phase III trials are necessary for confirmation of this hypothesis.     

诱导化疗联合三维适形放疗治疗48例局部晚期非小细胞肺癌

[目的]评价诱导化疗加三维适形放射治疗（3DCRT）治疗局部晚期非小细胞肺癌（NSCLC）的疗效及毒副反应。[方法]经病理学或细胞学确诊的78例局部晚期NSCLC患者随机分为单纯3DCRT治疗组（RT组，30例）和诱导化疗与3DCRT联合治疗组（CMT组，48例）。CMT组在3DCRT治疗前给予2～4个周期以铂类药物为主的静脉化疗。[结果]全组中位生存期12．5个月，CMT组中位生存期15个月，RT组中位生存期10个月（P=0．453）。1年生存率CMT组为70．8％，RT组为43．3％（P=0．016）：2年生存率CMT组为37．5％，RT组为26．6％（P=0．323）。两组毒副反应相似，化疗的毒副反应患者能耐受。[结论]诱导化疗加三维适形放疗治疗晚期NSCLC可延长生存期，但并不增加放射副反应。     

Clinical stages I and II Hodgkin's disease: a specifically tailored therapy according to prognostic factors

The H5 program in clinical stage (CS) I to II supradiaphragmatic Hodgkin's disease (HD) was tailored to prognostic factors identified in former European Organization for the Research and Treatment of Cancer (EORTC) studies. Among the 494 adult patients included in the study, the 237 patients belonging to the favorable group (H5F) underwent a staging laparotomy (Sx) in order to select the patients who could be treated with limited radiotherapy (RT) only. Thus, 198 patients (84%) with negative laparotomy were treated with RT alone and randomized to either mantle irradiation (M) or extended field mantle plus para-aortic (M + PA) irradiation. Complete remission (CR) was achieved in 99% of the patients. There was no difference in the 6-year relapse-free survival (RFS) rate (74% and 72%, respectively) or survival rate (96% and 89%). Therefore, Sx helped to define those patients who could be treated with M alone in contrast to those who required more aggressive therapy. The 39 patients with positive laparotomy were treated as the unfavorable group (H5U) from onset and randomized to either total/subtotal nodal irradiation (TNI/STNI) or a sandwiched mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) X 3, M irradiation, MOPP X 3 protocol (3M). Although the RFS rate was higher in the 3M arm (100% v 53%; P = .002), the 6-year survival was not significantly different between the two arms (overall, 92%). In the 257 patients with initial unfavorable disease, the Sx was avoided. They were randomized to either TNI/STNI or 3M. In complete responders (96%), the 6-year RFS was 91% in the 3M arm and 77% in the TNI/STNI arm (P = .02). The pattern of failure differed in the two arms: the inverted Y and spleen irradiation controlled occult infradiaphragmatic disease better than MOPP; conversely, less patients begun on MOPP recurred in the involved mantle areas. The difference in 6-year actuarial total survival (TS) (89% and 82%; P = .05 in favor of the 3M arm) was not retrieved after exclusion of the unrelated deaths from the analysis. The two arms produced similar TS in patients under 40 years of age. TNI retains interest, especially in young men wishing to preserve fertility. The overall result shows that when treatment is tailored to initial prognostic factors, excellent results can be obtained in all patient subgroups at minimal morbidity and toxic cost.     

150例早期霍奇金淋巴瘤的综合治疗

目的 对比单纯化疗、单纯放疗与综合治疗对早期霍奇金淋巴瘤(HL)的疗效.方法 回顾性分析150例Ⅰ期或Ⅱ期(早期)HL患者的临床资料,按照初次治疗方式分为单纯化疗组(22例)、单纯放疗组(18例)、化疗联合放疗的综合治疗组(109例)和手术组(1例).化疗方案以ABVD和MOPP为主,放疗方式主要包括受累野放疗、扩大野放疗和次全淋巴结照射.结果 结节硬化型、混合细胞型、淋巴细胞为主型、淋巴细胞消减型和结节性淋巴细胞为主型HL分别为84、39、23、3和1例.全组有72例患者资料完整,可判断预后,其中以欧洲癌症研究和治疗组织及德国霍奇金淋巴瘤研究组标准判断为0分者分别占36.1%和29.2%.全组完全缓解33例,部分缓解109例,疾病稳定5例,疾病进展3例.全组中位随访71.5个月,6年治疗失败率为18.8%,7年总生存率为89.3%.单因素分析显示,综合治疗的疗效显著优于单纯化疗,结节硬化型和混合细胞型的治疗失败风险明显低于淋巴细胞为主型(均P＜0.05).多因素分析显示,治疗方式可以显著影响预后,单纯化疗发生治疗失败的风险是综合治疗的2.52倍(P=0.004).单因素和多因素分析均未发现总生存时间的影响因素.综合治疗组的急性不良反应发生率较单纯化疗组或单纯放疗组高,主要表现为白细胞减低、胃肠道反应和脱发.结论 对于早期HL,综合治疗可降低治疗失败风险,但不良反应较重.     

Stages IIB and IIIB Hodgkin's disease. Results of combined modality treatment.

Between April 1969, and December 1974, 23 IIB and 26 IIIB surgically staged patients with Hodgkin's disease were treated at the Joint Center for Radiation Therapy. Stage IIB patients received either mantle and para-aortic-splenic pedicle, or total modal irradiation (TNI) alone or with the addition of combination chemotherapy. Relapse-free survival is 83% and overall survival 88%. Eleven patients received combination chemotherapy in addition to mantle and para-aortic irradiation, and both the relapse-free and overall survival are 100%. Of the stage IIIB patients, seven received TNI alone with four relapses, and 19 were treated with TNI and MOPP with two relapses. These relapse rates are significantly different (p less than 0.05). The relapse-free and overall survival for all stage IIIB patients is 66% and 84% respectively. These data imply that irradiation alone is not adequate treatment for stage IIIB Hodgkin's disease, and that with the addition of combination chemotherapy both the disease-free and overall survival is similar to that of early stage Hodgkin's disease without systemic symptoms. The ideal management of stage IIB Hodgkin's disease is less certain; it is our plan to study the efficacy of combined modality treatment.     

Treatment of pathologically staged IIIA Hodgkin's disease

We have reviewed the records of 37 patients with pathologically staged IIIA Hodgkin's disease, treated from 1970 to 1982. Twenty patients were staged IIIA1 and 17 staged IIIA2. Treatment consisted of total nodal irradiation in 33 patients (eight of whom received adjuvant MOPP), and mantle plus para-aortic irradiation in four patients (all of whom received adjuvant MOPP). Five-year relapse-free survival (RFS) in patients without splenic involvement was 77% versus 49% for those with splenic involvement (p = 0.43). Five-year RFS in patients treated with irradiation and chemotherapy (RT/CT) was 76% vs. 47% for patients treated with irradiation alone (p = 0.12). RFS was not influenced by sex, mediastinal involvement by tumor, or anatomic substage. Overall survival (corrected for deaths due to intercurrent disease) for the entire group of patients was 92% at 5 years and 87% at 10 years. Sex, mediastinal or splenic involvement by tumor, therapy (RT vs. RT/CT), or anatomic substage did not significantly influence survival. We currently recommend RT/CT only for those patients with extensive splenic involvement and/or Stage IIIA2 disease. We feel that the poor prognosis of these patients justifies the use of RT/CT and its risk of second malignancies.     

Risk-adapted therapy for clinical stage I-II Hodgkin's disease: 7-years results of radiotherapy alone for low-risk disease, and ABVD and radiotherapy for high-risk disease

Treatment outcomes were documented for 204 adult patients with clinical Stage I-II Hodgkin's disease who were treated with risk-adapted ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) and radiotherapy (RT) at the Toronto-Sunnybrook Regional Cancer Centre between 1984 and 1994. Forty-nine patients with clinical Stage I disease (excluding bulky mediastinal presentations) and 50 patients with a combination of clinical Stage IIA disease, age 50 years or less, and favourable pathology (lymphocyte predominant or nodular sclerosing histology) were identified as low risk and treated with RT alone to 35 Gy. One hundred and five high-risk patients were treated with chemotherapy (86 with ABVD) followed by RT to 25 Gy. The 7-year cause-specific, overall and disease-free survivals were 95%, 90% and 75% respectively for the low-risk cohort, and 91%, 90% and 88% respectively for the high-risk cohort. In-field relapses accounted for 50% of the failures in both groups. Sixteen of 24 (67%) patients with RT failure and 6/14 (43%) with combined modality therapy (CMT) failure were salvaged. Twenty-eight per cent of the patients treated with RT and 21% of those treated with CMT developed hypothyroidism by 7 years. Fatal complications were recorded in 6% of the low-risk patients managed with RT and 8% of high-risk patients managed with CMT. Septic death and second malignancy accounted for the majority of treatment-related fatalities. Risk-adapted therapy emphasizing RT alone for selected patients with favourable prognostic factors and CMT based on ABVD provides excellent long-term disease control. Further treatment refinements, including the wider application of CMT with lower doses of chemotherapy and RT, will be required to reduce the rate of fatal complications to more acceptable levels.     

Trials in advanced Hodgkin's disease: more than 30 years experience of the British National Lymphoma Investigation

Hodgkin's disease demonstrates an exquisite sensitivity to chemotherapy and radiation therapy. This necessitates investigation of modes of delivering these modalities in the best possible fashion to improve outcomes. The British National Lymphoma Investigation (BNLI) has conducted randomized trials in advanced Hodgkin's disease for > 30 years. The results of BNLI studies have demonstrated that MOPP (mechlorethamine/vincristine/procarbazine/prednisone) chemotherapy is superior to MOP (mechlorethamine/vincristine/procarbazine) chemotherapy; that there are no significant differences between MOPP and B-MOPP (MOPP plus bleomycin); that there is no significant benefit from maintenance therapy with lomustine/vinblastine/bleomycin; that LOPP (chlorambucil/vincristine/procarbazine/prednisone) is as effective as MOPP and has less acute toxicity; that alternating therapy with LOPP and EVAP (etoposide/vinblastine/doxorubicin/prednisolone) is superior to EVAP alone or hybrid LOPP and EVA (etoposide/vinblastine/doxorubicin); that alternating therapy with ChlVPP (a substitute for MOPP) and prednisolone/doxorubicin/bleomycin/vincristine/etoposide regimens is superior to the latter regimen alone; that the Stanford V regimen (doxorubicin/vinblastine/mechlorethamine/vincristine/bleomycin/etoposide/prednisone) combined with disciplined radiation therapy is safe and effective; that hybrid therapy with ChlVPP and EVA and alternating therapy with ChlVPP and prednisolone/doxorubicin/bleomycin/vincristine/etoposide are as effective as ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) alone; and that there is no additional benefit from total nodal irradiation or combined-modality therapy compared with MOPP; and that treatment with high-dose BEAM (carmustine/etoposide/cytarabine/melphalan) and autologous bone marrow transplantation is superior to mini-BEAM (lower-dose BEAM not requiring bone marrow rescue) for poor-risk relapsed and refractory disease.     

The role of radiation therapy in Hodgkin disease: experience and controversy. The 54th annual Janeway Lecture: 1989.

BACKGROUND. Beginning in 1970, a series of patients with Hodgkin disease were treated at the University of Minnesota, after staging laparotomy, with radiation therapy (RT) for Stage I, II, and IIIA Hodgkin disease. This report is an analysis of the results of the treatment and of treatment modifications. METHODS. From 1970 to 1974, all patients were treated with standard RT. In 1975, an analysis of these patients indicated that patients with large mediastinal mass (LMM) and patients with Stage IIIA spleen-positive (IIIAS+) disease had a higher recurrence rates than patients without these factors. Subsequently, a schema of radical radiation therapy (RRT) was devised, which included low-dose lung RT for patients with LMM and low-dose liver RT for patients with IIIAS+ disease. RESULTS. Analysis of the results of the two treatments indicates that the use of low-dose lung RT in patients with LMM and low-dose liver RT in patients with IIIAS+ Hodgkin disease produced survival and recurrence-free survival results equivalent to those achieved by use of combined modality treatment (CMT) or chemotherapy (CT) alone. CONCLUSIONS. The use of RT with whole lung and liver irradiation for patients with LMM and IIIAS+ Hodgkin disease, respectively, produces results that are equivalent to those of CMT or CT alone with the advantage of a decreased incidence of second malignant neoplasms. In addition, patients who do not respond to initial RT have a greater chance of being saved with chemotherapy than do patients initially treated with CMT of being saved with RT. The authors suggest that radical RT is the treatment of choice for patients with LMM and/or IIIAS+ Hodgkin disease.     

Capecitabine and radiation therapy preceded and followed by combination chemotherapy in advanced pancreatic cancer

PURPOSE: The primary objective of this study was to evaluate the tolerance and toxicity of radiation therapy (RT) and capecitabine in patients with advanced, unresectable pancreatic carcinoma. To control micrometastatic disease, combination chemotherapy (gemcitabine and cisplatin) before and after combined modality therapy (CMT) was planned. METHODS AND MATERIALS: Patients with unresectable or metastatic pancreatic cancer were eligible. Gemcitabine 1000 mg/m2 and cisplatin 35 mg/m2 were administered on Days 1 and 8 of a 21-day cycle for two cycles. RT was then given to a dose of 50.4 Gy in 1.8 Gy fractions. Patients were treated with capecitabine 1330 mg/m2 daily during RT. After CMT, two additional cycles of gemcitabine and cisplatin completed the treatment. RESULTS: Twenty-three patients were treated. Eighteen patients completed CMT. One patient was removed from study during CMT for toxicity issues. Treatment delays and dose reductions were common during the final two cycles of gemcitabine and cisplatin as a result of myelosuppression. Median survival was 10.1 months (95% confidence interval [CI] = 7.6, 13.7) for all 23 patients and 12.8 months (95% CI = 8.2, 18.9) for 18 patients without metastasis. CONCLUSION: Combined modality therapy with RT and capecitabine was well tolerated. Chemotherapy after CMT was difficult to complete owing to cumulative myelosuppression. Survival, response, and toxicity were comparable to infusional 5-fluorouracil and RT.     

Primary non-Hodgkin's lymphoma of bone.

Primary non-Hodgkin's lymphoma of bone (PLB) constitutes approximately 5% of all extranodal non-Hodgkin's lymphoma (NHL) and 7% of primary bone tumors. The peak incidence for PLB is in the fifth decade, with a slight preponderance of males over females. The presenting symptoms usually consist of localized bone pain and occasionally a palpable mass. Most patients with PLB have B-cell tumors with a diffuse mixed-cell or diffuse large cell histology. While most patients present with early-stage disease, it is not clear whether such patients benefit from combined-modality therapy (CMT) consisting of radiation therapy (RT) and chemotherapy (CT) compared with either RT or CT alone. However, there is strong evidence that CMT is beneficial in the treatment of localized NHL, and these results might be applicable to the therapy for PLB. Nevertheless, only a phase III randomized, controlled clinical trial will determine whether CMT is superior to either CT or RT alone.     

Cosmetic results after surgery, chemotherapy, and radiation therapy for early breast cancer

Adjuvant chemotherapy (CT) is increasingly being used in conjunction with radiation therapy (RT) in the treatment of early stage breast cancer. To assess the effect of CT on the cosmetic outcome of the irradiated breast, we retrospectively reviewed the cosmetic results of patients who received either cyclophosphamide-methotrexate-fluorouracil (CMF) or doxorubicin-based chemotherapy in conjunction with breast irradiation between 1968 and 1985. The overall cosmetic results were evaluated by the physician as "excellent," "good," "fair," or "poor" using a standardized scale. The CT group consisted of 170 patients treated with CT and RT administered either concurrently or sequentially (CT before RT, after RT, or both) with a minimum of 24 months of cosmetic follow-up. These were compared to an RT alone control group of 170 patients who did not receive CT and were matched by tumor size, radiation technique, and year of treatment. At 36 months, the cosmetic scores for the CT group compared to RT alone were 47% versus 71% excellent (p less than 0.01), 36% versus 19% good, and 17% versus 9% fair or poor. For the 50 patients treated with concurrent CMF and RT, the scores were 31% excellent, 45% good, and 24% fair/poor, whereas for the 118 patients treated with sequential RT and CT they were 54%, 31%, and 14%, respectively. There was no difference between those patients who received sequential CMF and those treated with doxorubicin. We conclude that adjuvant chemotherapy adversely affects the cosmetic outcome of breast irradiation, but that this effect is not clinically significant unless CMF is administered concurrently with RT. Patients treated with either sequential CMF or doxorubicin-based CT had only a slight decrement in their cosmetic result compared to patients treated without CT.