Early Stage Hodgkin's Disease Research Articles

Pathfinders in oncology from the first clinical use of single-agent chemotherapy to the introduction of mammography.

During the period from 1942 to 1962, treatment attempts with single-agent chemotherapy such as nitrogen mustard and urethan gained limited application. However, the groundbreaking success with aminopterin in the treatment of patients with pediatric acute leukemia and methotrexate in the treatment of gestational choriocarcinoma established single-agent chemotherapy as a pioneering contribution to oncology. The landmark discovery that early-stage Hodgkin disease is curable with radiation made radiotherapy into an essential specialty of oncology. Although radical surgical treatment dominated the field of surgery, the excision of localized cancers with or without adjuvant radiation emerged as new modality in therapy. Cytopathology and surgical pathology became new fields in medicine and pathologists became an integral part of the preoperative, intraoperative, and postoperative care of patients with cancer. The discovery of multiple new drugs demonstrated promising results and widened the field of oncology from the laboratory to the clinic. In the etiology of cancer, precancerous conditions were named and carcinoma of the lung was definitively linked to cigarette smoking. All things considered, the progress made between 1942 and 1962 came about through the dedicated work of many individuals. However, there were 7 distinguished pathfinders (2 pathologists, 1 pediatric pathologist-oncologist, 1 radiation therapist, 1 physician-actuary, 1 gynecologist-oncologist, and 1 chemist) who, despite their different backgrounds, interests, and sex, made groundbreaking contributions to oncology.

Seven-year follow-up for energy/vitality outcomes in early stage Hodgkin's disease patients treated with subtotal lymphoid irradiation versus chemotherapy plus radiation: SWOG S9133 and its QOL companion study, S9208.

We describe 7years of follow-up for the energy/vitality outcome in early-stage Hodgkin's disease patients treated on a randomized clinical trial that compared subtotal lymphoid irradiation (STLI) with combined modality treatment (CMT) (SWOG 9133). Survivorship research questions involved the extent to which symptoms/side effects endured over a follow-up period of 7years for this early-stage patient group. Two hundred thirty-nine patients participated in the quality of life (QOL) companion study (SWOG 9208) and completed the SF-36 vitality scale, SF-36 health perception item, Cancer Rehabilitation Evaluation System-Short Form (CARES-SF), and symptom distress scale. This paper reports vitality outcome results obtained from randomization, 6months, and annually for 7years. To assess changes in vitality over time, we used linear mixed models with patient as a random effect. Patients receiving CMT had lower observed vitality at 6months than did the STLI patients (p < .0001). However, beginning at year 1, vitality results did not differ significantly by treatment over the 5-year (p = .13) and 7-year (p = .16) follow-up periods. Vitality only slightly improved over baseline in either group after treatment. The results were similar after accounting for patterns of recurrence and missing data. This study demonstrated that patients with early-stage Hodgkin's disease experience a short-term (at 6months) decrease in vitality with treatment, which is more severe with CMT, but that after the first year, vitality scores were similar between the two treatment groups. Enduring fatigue results for patients receiving these therapies were not observed. Implications for cancer survivors These data provide comprehensive 7-year follow-up vitality information, an important symptom for early-stage lymphoma survivors.

Paediatric Hodgkin Lymphoma and Radiation Therapy: 3DCRT vs VMAT. A Case Report

Hodgkin Lymphoma (HL) is one of the most common cancers in young adult. Early stage Hodgkin disease has a good prognosis and high survival rates with modern therapeutic approaches. Clinical management of early stage HL involves two therapeutic options: one is combined modality therapy with abbreviated chemotherapy plus involved field radiation therapy (IFRT) and the other is chemotherapy alone. Combined modality ensures high cure rates but exposes young HL survivors to short-term and long-term complications such as cardiovascular and pulmonary disease and second malignancies especially in case of mediastinal involvement. Radiation therapy is crucial in the management of HL and has changed over the last decades. The introduction of new irradiation techniques such as Intensity modulated Radiation Therapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT), the delivery of lower doses regimens and the reduction of field sizes from extended field radiotherapy (EFRT ) to involved field RT (IFRT) and involved –nodal RT (INRT) allow to choose the most effective and safest technique. We present a case report of a paediatric HL, stage II bulky mediastinal, already treated with different chemotherapy regimens containing bleomicyn and candidate to autologous transplantation in order to demonstrate which radiation technique is more effective and safer for lungs between 3D conformational therapy (3DCRT) and VMAT. VMAT seems safer for better lung sparing.

Delivery of Radiation Therapy of Large Target Volumes in Hodgkin's Lymphoma Using IMRT Technique: A Dosimetric Case Study

Radiation therapy techniques for early stage Hodgkin's disease (HD) include simple parallel-opposedpair (POP) and Intensity-Modulated Radiation Therapy (IMRT). This case report compared the dosimetry achieved with POP and IMRT by evaluating target volumes and organs at risk (OAR). It showed that the IMRT technique could be a valuable technique when treating HD. Optimal target coverage can be achieved while at the same time reducing dose given to critical structures such as lung and thyroid.

Early-Stage Hodgkin Disease: The Utilization of Radiation Therapy and Its Impact on Overall Survival

Early-Stage Hodgkin Disease: The Utilization of Radiation Therapy and Its Impact on Overall Survival

Decrease in the Incidence of Second Malignancies in Patients With Early-Stage Hodgkin Disease Treated in the Modern Radiotherapeutic Era

Decrease in the Incidence of Second Malignancies in Patients With Early-Stage Hodgkin Disease Treated in the Modern Radiotherapeutic Era

18F-fluorodeoxyglucose positron emission tomography-positive sarcoidosis after chemoradiotherapy for Hodgkin’s disease: a case report

IntroductionThe occurrence of granulomatous disease in the setting of Hodgkin's disease is rare; however, when it occurs it can pose significant clinical and diagnostic challenges for physicians treating these patients.Case presentationWe report the case of a 33-year-old Caucasian woman of Mediterranean descent with newly diagnosed 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) scan-positive, early-stage Hodgkin's disease involving the cervical nodes who, despite having an excellent clinical response to chemotherapy, had a persistent 18F-FDG PET scan-positive study, which was suggestive of residual or progressive disease. A subsequent biopsy of her post-chemotherapy PET-positive nodes demonstrated sarcoidosis with no evidence of Hodgkin's disease.ConclusionThis case highlights the fact that abnormalities observed on posttherapy PET/CT scans in patients with Hodgkin's disease are not always due to residual or progressive disease. An association between Hodgkin's disease and/or its treatment with an increased incidence of granulomatous disease appears to exist. Certain patterns of 18F-FDG uptake observed on PET/CT scans may suggest other pathologies, such as granulomatous inflammation, and because of the significant differences in prognosis and management, clinicians should maintain a low threshold of confidence for basing their diagnosis on histopathological evaluations when PET/CT results appear to be incongruent with the patient's clinical response.

Therapeutic challenges: Cancer and pregnancy.

e19668 Background: The incidence of cancer in pregnancy is rising. We report the outcome of 15 women treated at our institution over a 20-year period. Methods: Cases were identified and records reviewed. Results: Median age at diagnosis was 35 years (25–42), with median gestational age at presentation of 10 weeks (3–25). 3 (20%) had chemotherapy deferred- 2 had node negative, ER positive breast cancers who had surgery at diagnosis, with CMF post delivery, 1 patient with early stage Hodgkin's disease presented in the second trimester and received ABVD postpartum. 12 (80%) received chemotherapy while pregnant. 1 woman had Ewing sarcoma, 1 had limited stage small cell cancer of cervix, and 1 had stage 1c ovarian cancer. The other 9 women had large (mean 4 cm), high grade (89% gr III), high risk (67% node +) breast cancers, 8 of these women had surgery at diagnosis with adjuvant chemotherapy, 1 was locally advanced and received neoadjuvant chemotherapy. All 12 women received doxorubicin/cyclophosphamide q 21 days whilst pregnant. None were treated prior to 2nd trimester. A total of 54 cycles of chemotherapy were administered during pregnancy. The mean gestational age at delivery was 36 weeks (30–40). There were no spontaneous abortions or fetal malformations. 1 baby was born neutropenic but was well and recovered counts quickly. Postpartum, all women received further chemotherapy with or without radiotherapy as appropriate for their disease site and stage. At median follow-up 35 months (5–219), all 15 women are alive and clinically well; 14 (93%) are disease free. 1 patient with breast cancer had bone metastases on postpartum bone scan; she continues on zolendronic acid and is well at 3 years. There have been no developmental abnormalities reported in the children to date. Conclusions: Doxorubicin/cyclophosphamide can be safely administered beyond the first trimester. Although a heterogeneous group, there has been no apparent compromise of maternal oncologic outcome. Long-term follow up of these children for potential late toxicities is required. No significant financial relationships to disclose.

Efficacy of Abbreviated Stanford V Chemotherapy and Involved Field Radiotherapy in Early Stage Hodgkin's Disease: Mature Results of the G4 Trial.

Abstract 1670Poster Board I-696The standard management for early stage Hodgkin's disease (HD) is combined modality therapy. In the G4 protocol, patients (pts) with non-bulky, supra-diaphragmatic stage I-IIA disease received 8 weeks of Stanford V chemotherapy + 30 Gy involved field radiotherapy (IFRT).87 pts were enrolled and treated between 4/1996 and 4/2001. Median age was 30 years (16-59) and stages were IA (n=23), IIA (n=64). Unfavorable risk factors were present in 47 patients (54%) according to German Hodgkin Study Group (GHSG) criteria (> 2 AA sites, ESR > 50 or EN involvement) and 38 (44%) according to EORTC criteria (> 3 AA sites, ESR > 50). Therapy was well tolerated with grade 3-4 non-hematologic toxic events in 7 % of pts. These included constipation (n=3), peripheral neuropathy (n=1), generalized weakness (n=2), chest pain (n=1), mylagias (n=1), abdominal pain (n=1) and an allergic reaction to etoposide (n=1). 42 patients received cytokine support for grade 3-4 neutropenia however only 2 pts developed fever with neutropenia. No cases of clinical bleomycin toxicity or radiation pneumonitis were observed. At a median follow-up of 9 (2-12) years, freedom from progression (FFP) and survival (OS) are 94% and 96% respectively. FFP was 100% for favorable and 89% for unfavorable patients by GHSG criteria (p=0.04) with no differences in OS (96.9% versus 95.7%). All relapses (n=5) occurred in the RT field: limited in 2 patients and combined with distant disease in 3 pts. All relapses were in “unfavorable” risk patients: 5 per GHSG and 4 per EORTC criteria. Secondary therapy included chemotherapy followed by high dose therapy and stem cell support (n=3) and ABVD (n=2). Three pts died, 2 due to disease progression after second-line therapy and one due to metastatic colon cancer. 5 patients developed a second cancer (2 breast, 2 melanomas at unirradiated sites and 1 colon cancer). The cases of breast cancer were considered unrelated to RT as both occurred within 5-years of therapy in women who were > 30 yrs at time of treatment. No secondary AML and no late cardiac or pulmonary toxicities have been observed.In conclusion, for pts with non-bulky stage I/II A HD, abbreviated Stanford V with 8 weeks of chemotherapy and 30 Gy IFRT is a safe and highly effective regimen. It is still too early to assess potential RT-related complications. Our outcomes in “unfavorable” stage I-IIA patients without bulky or symptomatic disease compare favorably with more intensive or prolonged regimens employed by the GHSG and EORTC. DisclosuresNo relevant conflicts of interest to declare.

Utilization of radiation therapy in early-stage Hodgkin disease and its impact on survival

8511 Background: Despite numerous randomized trials confirming the benefit of consolidation radiation therapy (RT) in the management of early stage Hodgkin disease (HD), utilization of RT in this setting remains variable. We performed a population-based analysis to assess the utilization of RT and its impact on overall and cause specific survival. Methods: The surveillance, epidemiology and end results (SEER) registry was used to identify patients aged 15–75 years diagnosed between 1990–2004 with early stage (stage I-IIA/B) HD, excluding nodular lymphocyte predominant HD. Kaplan-Meier analysis was performed to evaluate the effect of RT on overall survival (OS) and cause-specific survival (CSS). Subgroup survival analyses were also performed by era of treatment (1990–1997 and 1998–2004), sex, and patient age (&lt;30, 30–50, and &gt;50 years). Results: A total of 9729 patients met inclusion criteria. Median age of all patients was 34 years. The majority (71.3%) had nodular sclerosis (NS) type HD. By clinical stage, 3399 (34.9%) were stage I, and 6330 (65.1%) were stage II. 5352 patients (55%) received RT. RT was more likely to be employed during the early era of treatment, in younger patients, females, non-Blacks, and in NS, mixed cellularity and lymphocyte-rich HD. For the entire cohort, RT was associated with a significant (p&lt;0.001) improvement in OS and CSS (hazard ratio of 0.537 and 0.437, respectively). The benefit of RT for OS and CSS remained significant for all subgroups analyzed including the era of treatment, sex, and age (p≤0.001). Conclusions: In this large population-based series of early stage HD patients, the use of RT is associated with a significant OS and CSS benefit across all subgroups. Current efforts in clinical trials have aimed at decreasing the utilization of RT among this patient population. This shift in practice is reflected in the data presented here. The omission of RT from the treatment paradigm, however, appears to be related with diminished survival. No significant financial relationships to disclose.

Early FDG-PET Scan Confirms Its Prognostic Impact Also in Localized Stage, ABVD Treated Hodgkin Lymphoma Patients.

Background: Hodgkin's lymphoma is one of the maligant diseases with the highest rate of cure particularly if diagnosed in early stage. Nevertheless a small proportion of patients with localized stage do not respond to therapy and become chemorefractory. FDG-PET clearly showed the high predictive value in identifing patients with bad prognosis in advanced stages. The aim of this prospective study was to evaluate the prognostic value of FDG-PET in patients with localized Hodgkin's disease.Patients: From 2002, 122 new localized stage Hodgkin's lymphoma patients were consecutively admitted to seven Italian hematological centers on behalf of Intergruppo Italiano Linfomi. Patients with stage I-IIA according to Ann Arbor stage, independent of presence of bulky disease, were considered for the study. FDG-PET was mandatory at baseline, after two cycles (immediately before the start of the third cycle) and at the end of therapy. We evaluated the progression free survival of patients starting from the time of diagnosis to relapse or progression of disease or last follow-up. Patients were candidate to receive 3 or 4 course of ABVD followed by involved field radiotherapy at 30 Gy, except in the cases in which physician decided to omit radiotherapy due to excess of toxicity. All patients were given the planned therapy except in case of overt progression. All patients were treated with ABVDResults: The median age was 31 years (16–75), 63 patients were female and 59 male, 10 patients presented stage I and 112 stage II, bulky was reported in 29 patients. One-hundred and ten patients were treated with combined modality (CT+RT) and 12 patients were treated with chemotherapy alone (all with 6 cycles). One hundred and eleven patients attained CR while 11 were chemoresistent: 6 showed disease progression during CT and 5 showed an early relapse. The FDG-PET performed after two cycles (PET2) was positive in 18 patients (15%) and the FDG-PET performed at the end of therapy was positive in 12 patients. Fourteen patients showed disease progression during therapy or within 6 months after having reached CR, three patients died due to the disease. In univariate analysis negative FDG-PET performed after two cycles (p .0000), absence of bulky disease at diagnosis (.003) and the use of radiotherapy (.0006) were statistically correlated with a better progression free survival. In multivariate analysis only PET2 was independently predictive of relapse/progression probability (p .007). With a median follow-up of 29 months (range 6–79) 119 patients are alive and 108 (88%) are free from progression. The 2-yr FFS probability for PET2 negative and for PET2 positive patients were 95% and 46% respectivelyConclusion: This prospective and multicentric study confirms that FDG-PET scan performed after two courses of conventional standard dose chemotherapy was able to predict treatment outcome in early stage Hodgkin disease.

WITHDRAWN: Interventions for early stage Hodgkin's disease in children.

Hodgkin's disease is one of the most curable cancers in children, particularly at the early stages. However it is not clear which combinations of treatment strategies are most effective at maintaining high cure rates and minimising long term harmful effects or sequelae of treatment. To assess the effects of radiotherapy, chemotherapy or combined radiotherapy and chemotherapy on relapse free survival and overall survival rates in children with early (stage I to IIA) Hodgkin's disease. We searched the Cochrane Library (issue 4, 2001), MEDLINE (1966 to July 2001), EMBASE, Cinahl, Cancer-CD and reference lists of relevant articles. We also handsearched six journals. Randomised controlled trials of involved field radiotherapy, extended field radiotherapy, anthracycline based chemotherapy regimens, or alkylating chemotherapy agents in children to 19 years of age with Hodgkin's disease. Trial eligibility and quality were assessed and study authors were contacted for additional information. Four trials involving 334 children were included. It was not possible to combine the outcomes as they covered different treatment regimens. The trials were of variable quality. One trial comparing radiotherapy alone showed no discernible difference in relapse free survival (relative risk 0.73, 95% confidence interval 0.49 to 1.09) or overall survival (relative risk 0.92, 95% confidence interval 0.79 to 1.07) between involved field and extended field radiotherapy. No discernible difference was found between involved field radiotherapy plus chemotherapy and extended field radiotherapy and chemotherapy (based on one small trial). In another trial, involved field radiotherapy plus chemotherapy appeared to increase relapse free survival compared to either involved field or extended field radiotherapy alone, although a discernible difference was found for overall survival. Extended field radiotherapy alone appeared to increase relapse free survival compared to extended radiotherapy plus chemotherapy (relative risk 0.34, 95% confidence interval 0.14 to 0.83) but no discernible difference was apparent for overall survival (based on one trial). There is little evidence from randomised controlled trials to evaluate the consensus approach of short course chemotherapy and local radiotherapy, although no discernible difference in survival was detected between involved field and extended field radiotherapy in one randomised trial.

Unilateral and Bilateral Breast Cancer in Women Surviving Pediatric Hodgkin's Disease

To define demographic and therapeutic associations with the risk of breast cancer in children treated for Hodgkin's disease (HD), particularly the frequency and interval to the development of contralateral breast cancer. All 398 female patients (<19 years) treated for HD in five institutions during the accrual period were evaluated. Mean follow-up was 16.9 years. The standardized incidence ratio (SIR) was calculated as the ratio of the observed number of cases to the expected number of cases, estimated using age-matched controls from the Surveillance, Epidemiology, and End Results database. A total of 29 women developed breast cancer (25 invasive, 4 ductal carcinoma in situ; SIR, 37.25; 95% confidence interval, 24.96-53.64). Time to diagnosis was 9.4 to 36.1 years. Cumulative incidence was 24% at 30 years. Ten patients (34%) had bilateral disease (9 metachronous, 1 synchronous). The interval to contralateral breast cancer was 12 to 34 months. On univariate analysis, significant variables included stage of HD, mantle radiation dose, pelvic radiation (protective), and follow-up time. On multivariate analysis, early stage and older age at diagnosis of HD (<or=12 vs. >12 years) were significant predictors of secondary breast cancer. Women surviving pediatric HD were found to have a 37-fold increase in the risk of breast cancer and a high likelihood of rapidly developing bilateral disease. Early-stage HD and age greater than 12 years at diagnosis of HD were independent risk factors. Higher radiation doses may augment risk, and pelvic radiation may be protective. Breast cancer screening methodology and frequency, plus the role of prophylaxis in patients with unilateral disease, require definition.

Chemoradiotherapy in early-stage Hodgkin's disease.

Chemotherapy plus involved-field radiotherapy (IFRT) should be standard treatment for Hodgkin's disease that has a favourable prognosis, according to two multicentre randomised trials (N Engl J Med 2007; 357: 1916–27).

Chemotherapy plus Involved-Field Radiation in Early-Stage Hodgkin's Disease

BACKGROUND: Treatment of early-stage Hodgkin's disease is usually tailored in line with prognostic factors that allow for reductions in the amount of chemotherapy and extent of radiotherapy required for a possible cure. METHODS: From 1993 to 1999, we identified 1538 patients (age, 15 to 70 years) who had untreated stage I or II supradiaphragmatic Hodgkin's disease with favorable prognostic features (the H8-F trial) or unfavorable features (the H8-U trial). In the H8-F trial, we compared three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) combined with doxorubicin, bleomycin, and vinblastine (ABV) plus involved-field radiotherapy with subtotal nodal radiotherapy alone (reference group). In the H8-U trial, we compared three regimens: six cycles of MOPP-ABV plus involved-field radiotherapy (reference group), four cycles of MOPP-ABV plus involved-field radiotherapy, and four cycles of MOPP-ABV plus subtotal nodal radiotherapy. RESULTS: The median follow-up was 92 months. In the H8-F trial, the estimated 5-year event-free survival rate was significantly higher after three cycles of MOPP-ABV plus involved-field radiotherapy than after subtotal nodal radiotherapy alone (98% vs. 74%, P<0.001). The 10-year overall survival estimates were 97% and 92%, respectively (P=0.001). In the H8-U trial, the estimated 5-year event-free survival rates were similar in the three treatment groups: 84% after six cycles of MOPP-ABV plus involved-field radiotherapy, 88% after four cycles of MOPP-ABV plus involved-field radiotherapy, and 87% after four cycles of MOPP-ABV plus subtotal nodal radiotherapy. The 10-year overall survival estimates were 88%, 85%, and 84%, respectively. CONCLUSIONS: Chemotherapy plus involved-field radiotherapy should be the standard treatment for Hodgkin's disease with favorable prognostic features. In patients with unfavorable features, four courses of chemotherapy plus involved-field radiotherapy should be the standard treatment. (ClinicalTrials.gov number, NCT00379041 [ClinicalTrials.gov].).

Chemotherapy plus Involved-Field Radiation in Early-Stage Hodgkin's Disease

Treatment of early-stage Hodgkin's disease is usually tailored in line with prognostic factors that allow for reductions in the amount of chemotherapy and extent of radiotherapy required for a possible cure. From 1993 to 1999, we identified 1538 patients (age, 15 to 70 years) who had untreated stage I or II supradiaphragmatic Hodgkin's disease with favorable prognostic features (the H8-F trial) or unfavorable features (the H8-U trial). In the H8-F trial, we compared three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) combined with doxorubicin, bleomycin, and vinblastine (ABV) plus involved-field radiotherapy with subtotal nodal radiotherapy alone (reference group). In the H8-U trial, we compared three regimens: six cycles of MOPP-ABV plus involved-field radiotherapy (reference group), four cycles of MOPP-ABV plus involved-field radiotherapy, and four cycles of MOPP-ABV plus subtotal nodal radiotherapy. The median follow-up was 92 months. In the H8-F trial, the estimated 5-year event-free survival rate was significantly higher after three cycles of MOPP-ABV plus involved-field radiotherapy than after subtotal nodal radiotherapy alone (98% vs. 74%, P<0.001). The 10-year overall survival estimates were 97% and 92%, respectively (P=0.001). In the H8-U trial, the estimated 5-year event-free survival rates were similar in the three treatment groups: 84% after six cycles of MOPP-ABV plus involved-field radiotherapy, 88% after four cycles of MOPP-ABV plus involved-field radiotherapy, and 87% after four cycles of MOPP-ABV plus subtotal nodal radiotherapy. The 10-year overall survival estimates were 88%, 85%, and 84%, respectively. Chemotherapy plus involved-field radiotherapy should be the standard treatment for Hodgkin's disease with favorable prognostic features. In patients with unfavorable features, four courses of chemotherapy plus involved-field radiotherapy should be the standard treatment. (ClinicalTrials.gov number, NCT00379041 [ClinicalTrials.gov].).

IXB.1 Treatment of indolent lymphoma in medically non-fit patients

The majority of patients with early-stage (IA–IIA) Hodgkin's disease (HD) can at present be cured by current available therapeutic options. Actually the “gold standard” for patients with early-stage HD is a combined approach consisting of a short-duration chemotherapy (e.g., two to four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine; ABVD) and low-dose (20–30 Gy) involved-field irradiation (IF-RT).The treatment of choice for advanced-stage HD is still represented by chemotherapy alone or followed by RT. At present, it is internationally accepted that ABVD should be the standard regimen.High-dose chemotherapy (HDC) with peripheral-blood stem-cell support (PBSCs) represents the treatment of choice for patients relapsing after chemotherapy, but, nevertheless, about 50% of transplanted patients relapse or progress after HDC.Regarding low- and high-grade non-Hodgkin's lymphomas, Rituximab associated or not to chemotherapy, is much more extensively used. In advanced low-grade lymphomas the role of immunochemotherapy has been definitively demonstrated in a phase III study, comparing eight courses of rituximab plus chemotherapy (CVP regimen) versus CVP alone at diagnosis. Three courses of CHOP plus Rituximab associated to involved fields radiotherapy (RT) is considered to be the standard treatment in localized high-grade lymphoma. In advanced disease patients, intensified CHOP-like regimen and new therapeutic agents have been tried to improve the clinical results in newly diagnosed patients with encouraging results. Finally, several studies confirmed the usefulness of prognostic scores as IPI for high-grade lymphoma and FLIPI for follicular lymphoma, and the usefulness of PET in the staging of lymphomas.

IXB.2 Treatment of aggressive lymphoma in medically non-fit patients

The majority of patients with early-stage (IA–IIA) Hodgkin's disease (HD) can at present be cured by current available therapeutic options. Actually the “gold standard” for patients with early-stage HD is a combined approach consisting of a short-duration chemotherapy (e.g., two to four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine; ABVD) and low-dose (20–30 Gy) involved-field irradiation (IF-RT).The treatment of choice for advanced-stage HD is still represented by chemotherapy alone or followed by RT. At present, it is internationally accepted that ABVD should be the standard regimen.High-dose chemotherapy (HDC) with peripheral-blood stem-cell support (PBSCs) represents the treatment of choice for patients relapsing after chemotherapy, but, nevertheless, about 50% of transplanted patients relapse or progress after HDC.Regarding low- and high-grade non-Hodgkin's lymphomas, Rituximab associated or not to chemotherapy, is much more extensively used. In advanced low-grade lymphomas the role of immunochemotherapy has been definitively demonstrated in a phase III study, comparing eight courses of rituximab plus chemotherapy (CVP regimen) versus CVP alone at diagnosis. Three courses of CHOP plus Rituximab associated to involved fields radiotherapy (RT) is considered to be the standard treatment in localized high-grade lymphoma. In advanced disease patients, intensified CHOP-like regimen and new therapeutic agents have been tried to improve the clinical results in newly diagnosed patients with encouraging results. Finally, several studies confirmed the usefulness of prognostic scores as IPI for high-grade lymphoma and FLIPI for follicular lymphoma, and the usefulness of PET in the staging of lymphomas.

Early-stage Hodgkin's disease can be treated successfully with mantle irradiation alone

Early-stage Hodgkin's disease can be treated successfully with mantle irradiation alone

A Prospective Trial of Radiation Alone vs Combination Chemotherapy Alone for Early-Stage Hodgkin's Disease: Implications of 25-Year Follow-Up to Current Combined Modality Therapy.

We conducted a prospective randomized trial comparing radiation therapy to MOPP chemotherapy in patients with stages IA through IIIA Hodgkin's disease (HD). Patients with peripheral stage IA disease received radiation therapy without randomization. Median follow-up is now 25 years. Among the 30 patients with peripheral stage IA disease, all achieved complete response, 4 relapsed (13%), 8 died [27%; 2 from HD, 1 suicide, 1 myocardial infarction (MI), and 4 from second malignancies). Among the 51 patients randomized to receive radiation, 49 (96%) achieved complete response, 19 relapsed (39%), 18 died (35%; 10 from HD, 1 AIDS, 1 anorexia nervosa, 1 pulmonary fibrosis, 3 congestive heart failure, and 2 from second malignancies). In addition, 7 other second cancers have been observed in 6 patients treated with radiation who are alive and significant treatment toxicities affect the lives of 5 others. Among the 54 patients randomized to receive MOPP chemotherapy, 52 (96%) achieved complete response, 7 relapsed (13%), 10 died [18%; 5 from HD, 2 MI (1 in cycle 1), 1 from Pneumocystis pneumonia during treatment, and 2 from second malignancies]. Two other patients are alive with a second cancer and one has AIDS. Disease-free survival is 87% for MOPP and 61% for radiation in the randomized arms at 25 years (p=0.0034). Overall survival is 81% for MOPP and 63% for radiation in the randomized arms at 25 years (p=0.048). When the peripheral IA patients are added to the randomized radiation-treated patients, disease-free survival is 70% (p=0.36 vs MOPP) and overall survival is 67% (p=0.07 vs MOPP). The design of the study permits an analysis of the late effects associated with the administration of radiation alone or MOPP alone as a substantial fraction of patients achieved complete response and remained in their initial remission. Among all patients treated with radiation, 11 died in first remission (5 from a second cancer, 2 from CHF, 1 MI, 1 pulmonary fibrosis, 1 AIDS, 1 suicide). Among all patients treated with MOPP, 3 died in first remission (2 from a second cancer, 1 MI). The difference in survival after achieving initial CR (93% for MOPP, 78% for radiation) is significant (p=0.054). The current standard practice of using combined modality therapy might be expected to incur the toxicities associated with both chemotherapy and radiation therapy. Furthermore, synergistic toxicities associated with the combination have been described. Thus, efforts should be made to define the substantial fraction of patients whose disease can be controlled with a single modality and reserve combined modality therapy for the subset that requires it for disease control.