Subtotal Lymphoid Irradiation Research Articles

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.

Subtotal Lymphoid Irradiation in the Treatment and Prevention of Pediatric Cardiac Allograft Rejection: A 17-year Experience

Subtotal Lymphoid Irradiation in the Treatment and Prevention of Pediatric Cardiac Allograft Rejection: A 17-year Experience

Autologous Stem Cell Transplant Is a Feasible Treatment For Older Relapsed and Refractory Hodgkin Lymphoma Patients

BackgroundRelapsed or refractory Hodgkin lymphoma in younger patients is routinely treated with platinum-based salvage chemotherapy and response is consolidated with high-dose therapy and autologous stem cell transplant (HDT/ASCT). Age >45y has been associated with inferior outcomes with first-line therapy, attributable to more aggressive biology, comorbid illnesses, reduced physiologic reserve, and heightened sensitivity to toxicities of therapy. Optimal management of older patients with relapsed or refractory HL is uncertain, as the safety and efficacy of consolidative HDT/ASCT have not been well described in this population. Patient and MethodsWe systematically reviewed all patients age ≥50 who underwent HDT/ASCT between January 1995 and August 2013 at MSKCC for relapsed or refractory HL; age 50 was selected to enrich for higher-risk patients. All patients had achieved either a complete response (CR) or partial response (PR) to second-line therapy, defined by CT and either gallium or 18FDG-PET. Center standard routinely requires adequate hepatic, renal, and cardiopulmonary reserve (left ventricular ejection fraction >50%, hemoglobin-adjusted diffusion capacity >50% predicted). Overall survival (OS) and event free survival (EFS) were calculated with Kaplan-Meier curves, and toxicity through day 100 was assessed by chart abstraction. Toxicities were graded according to the CTCAE version 4. Results42 patients age ≥50y were identified in a retrospective chart review of patients with relapsed or refractory HL treated with HDT/ASCT. Median age was 54.9y at transplant (range, 50.1-66.4 years old). Ten (24%) patients were ≥60y, 32 (76%) were 50-60y. At initial diagnosis, 24 patients (57%) had stage I-II disease and 18 patients (43%) had stage III-IV disease. All patients had classical HL histology. 38% of patients had primary refractory disease, 48% patients were in first relapse, and 14% had multiply relapsed disease. The most common second-line therapy was ifosfamide, carboplatin, and etoposide (78%). 32 patients (76%) had a CR to second-line therapy and proceeded to HDT/ASCT. 9 patients (21%) achieved a PR to second-line chemotherapy; of these, 2 converted to a CR with additional systemic therapy, 5 received definitive involved-field radiotherapy (IFRT), and 2 proceeded to HDT/ASCT in a PR. Patients required a mean of 2.4 days (range, 1-4) for peripheral blood stem cell mobilization. 18 (43%) of patients were conditioned with cyclophosphamide, etoposide, and carmustine (CBV), 17 (40%) with cyclophosphamide, etoposide, and total or subtotal lymphoid irradiation, 6 (14%) with carmustine, etoposide, cytarabine, and melphalan, and 1 (2%) with melphalan and etoposide. 55% of patients also received pre-transplant a hyperfractionated IFRT boost to the site of relapsed disease.At a median follow up of 46 months post-transplant, OS and EFS were 71% and 66%, respectively. Mean transplant admission duration was 17 days with 22% of patients requiring readmission within 100 days post-transplant. Mean time to neutrophil engraftment was 10 days, and mean time to platelet engraftment was 24 days; 22% of patients had delayed platelet recovery beyond 30 days post-transplant. 4 patients (10%) required intensive care for sepsis. The most common toxicities were gastrointestinal, including a combination of grade 2-3 mucositis, nausea, vomiting, and diarrhea in 98% of patients. 17 pts (40%) experienced grade 3 or 4 hypoxia during the transplant admission, but persistent pneumonitis did not occur in any pt. Bacteremia occurred in 16 pts (38%), but there were no deaths due to sepsis. Transplant related mortality was 2%, with one death prior to day 100 from respiratory failure and thromboembolic stroke. Assessment of the subgroup of 10 pts >60y showed similar OS and EFS outcomes to the cohort as a whole (P=NS). ConclusionsIn our single center experience treating patients age ≥50y with relapsed or refractory HL, HDT/ASCT is adequately tolerated and achieves outcomes comparable to our prior published outcomes in younger patients with similar second-line therapy and conditioning regimens (patients of median age 27 experienced an OS of 83% and EFS of 68% following HDT/ASCR, at a median follow-up of 43 months). HDT/ASCT should be routinely offered to older patients with relapsed or refractory HL who are otherwise suitable candidates for autotransplantation. Disclosures:No relevant conflicts of interest to declare.

Radiation dose-benefit analysis of hematopoietic stem cell grafting for tolerence induction across MHC barriers in living related donor renal allograft recipients

3044 Background: Donor specific immunologic tolerance protects an allograft from chronic rejection and allows discontinuation of chronic immunosuppressive therapy. Ahmedabad-tolerance induction protocol (A-TIP) allows grafting in living related donor (LRD) renal allograft recipients with persistent low-level MLHC. Present study aims to define of the ideal radiation dose needed for tolerance induction in patients undergoing A-TIP. Methods: 210 consecutive end stage renal disease patients recruited between May '05 through Mar '07 underwent renal transplantation (RTx) following A-TIP and negative Lymphocytotoxicity cross match (LCM). A-TIP includes (a) 2 DLI's (b) low intensity conditioning, and (c) HSC grafting.The conditioning regimen included fractionated low dose target specific radiation, cyclosporine, cyclophosphamide, anti T-cell a.b and treosulfan. All patients underwent subtotal lymphoid irradiation (STLI) targeting spleen, abdominal, iliac and inguinal lymph nodes, thoraco-lumbar vertebra and 75% of pelvis. Patients were randomized into 3 groups of 70 each: STLI 600, STLI 800, STLI 1000, corresponding to doses of 600cgy, 800cgy and 1000cgy delivered conventionally using 6MV/15MV photons. Unfractionated HSC procured from donor BM was administered into portal circulation, within 24 hours of achieving CD4+/CD8+ T cell count ≤ 10% of baseline. Donor specific cytotoxic antibodies were eliminated before RTx. Immunosuppression (ISp) was withdrawn 3–6 mo after RTx for patients with consistently positive chimerism. Tolerance - Robust (R), Prope (P) and Metastable (M) is defined as RT: Stable allograft function (fn.) for &gt;100 days without ISp; PT: Early adequate, stable grafts fn. with no rejection episodes on minimum ISp; MT: Adequate graft fn. on ISp with single episode of steroid responsive ac. rejection. Results: See Table. Conclusions: The safe and effective dose for tolerance induction in LRD renal transplantation is 1000 cGy. [Table: see text] No significant financial relationships to disclose.

Idiopathic Cholestasis as a Paraneoplastic Phenomenon in Hodgkin's Lymphoma

Paraneoplastic cholestasis is an uncommon presenting symptom in Hodgkin's lymphoma (HL). Two distinct entities causing this clinical picture have been described: idiopathic cholestasis and vanishing bile duct syndrome (VBDS). We report a patient with idiopathic cholestasis and early-stage HL with favorable risk factors whose liver biopsy results were consistent with intrahepatic cholestasis and no ductopenia. Other causes for cholestatic jaundice were ruled out. He was treated with subtotal lymphoid irradiation and subsequently experienced a steady improvement in his liver function tests to near normal over 21 months. This case illustrates a rare paraneoplastic phenomenon, and a review of the available literature is included. We also discuss the differences between HL-related idiopathic cholestasis and VBDS. The distinction between these 2 diseases has prognostic implications: idiopathic cholestasis is usually reversible in early-stage HL after treatment, whereas patients who develop VBDS commonly die from their disease. There is no established approach to the management of paraneoplastic cholestasis. We postulate that single-modality radiation therapy alone should be considered a valid treatment alternative in early-stage HL with idiopathic cholestasis.

Over 20 Years of Progress in Radiation Oncology: Hodgkin's Disease.

The Patterns of Care Study (PCS) surveys for Hodgkin's disease have documented important correlations between treatment processes and patient outcome. Nationwide improvements in radiotherapy for Hodgkin's disease since 1973, such as routine use of extended fields (subtotal lymphoid irradiation) in patients with early stage disease, individualized blocking, and treatment using linear accelerators, have resulted in greater freedom from relapse and overall survival for patients with stage I/II disease treated with radiotherapy alone. In addition, the introduction of computed tomography along with increased use of chemotherapy in high-risk patients has reduced the use of routine laparotomy and has improved outcome for patients with stage III disease. Overall survival for Hodgkin's disease in the national practice is excellent, reflecting the dissemination of complex treatment programs and radiation therapy technology to the oncologic community at large. Future studies of the national practice will be important in assessing the impact of managed care on workup and other facility practices, as well as evaluating the transfer of new approaches aimed at reducing treatment toxicities.

Combined Modality Treatment for Poor Prognosis Stages I and II Hodgkin's Disease.

Recommendations for the treatment of "poor prognosis" stages I and II Hodgkin's disease (HD) depend on the extent of staging. For centers that favor exploratory laparotomy and splenectomy, the standard treatment after negative surgical staging remains subtotal lymphoid irradiation. However, most centers recommend excluding selected patients from surgical staging. In particular, most specialists agree that patients with bulky mediastinal disease (large mediastinal adenopathy) should receive combined chemotherapy and radiotherapy without surgical staging. Centers that have eliminated staging laparotomy rely on clinical staging and have identified a number of poor prognostic factors that influence treatment recommendations. In 1995, the following factors were considered to be associated with an unfavorable prognosis in clinical stages (CS) I and II HD: advanced age, systemic symptoms, high erythrocyte sedimentation rate, large number of individual sites, and presence of bulky disease. For example, these factors have been used in the H7 and H8 European Organization for the Research and Treatment of Cancer trials and have been adopted by almost 100 participant groups. For CS I and II patients with unfavorable presentations, the literature suggests that the optimal treatment is a combination of chemotherapy and radiotherapy. Nevertheless, the optimal delivery of chemotherapy and radiotherapy is still debated and a number of the questions listed below are awaiting answers: 1. The chemotherapy schedule: Mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alone can no longer be recommended (for toxicity reasons) for the routine treatment of poor prognosis CS I and II HD. Many centers, on theoretical arguments, favor seven or eight drug combinations (MOPP/ABV hybrid), although the advantage of these combinations in toxicity and efficacy over doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone has not been demonstrated. 2. The number of chemotherapy courses: Most groups use six cycle regimens, but reduction to three to four cycles is currently being investigated both in pilot and randomized studies. 3. Timing of chemotherapy: Chemotherapy is given first in most instances. Whether or not a "sandwiched" scheme is better than all the chemotherapy given upfront remains to be answered. 4. Volumes to be irradiated: Data suggest that the irradiated volumes can be safely limited to initially involved lymph node regions after effective chemotherapy. The question is presently being addressed in a few ongoing randomized trials. 5. Radiation dose to be delivered: The decrease of the radiation dose to 35 to 36 Gy after effective chemotherapy has gained a wide acceptance. Further dose reduction is being investigated. In conclusion, except for selected CS I and II patients still referred for surgical staging, combined modality therapy appears to be the treatment of choice for poor prognosis CS I and II HD.

Over 20 years of progress in radiation oncology: Hodgkin's disease

The Patterns of Care Study (PCS) surveys for Hodgkin's disease have documented important correlations between treatment processes and patient outcome. Nationwide improvements in radiotherapy for Hodgkin's disease since 1973, such as routine use of extended fields (subtotal lymphoid irradiation) in patients with early stage disease, individualized blocking, and treatment using linear accelerators, have resulted in greater freedom from relapse and overall survival for patients with stage I/II disease treated with radiotherapy alone. In addition, the introduction of computed tomography along with increased use of chemotherapy in high-risk patients has reduced the use of routine laparotomy and has improved outcome for patients with stage III disease. Overall survival for Hodgkin's disease in the national practice is excellent, reflecting the dissemination of complex treatment programs and radiation therapy technology to the oncologic community at large. Future studies of the national practice will be important in assessing the impact of managed care on workup and other facility practices, as well as evaluating the transfer of new approaches aimed at reducing treatment toxicities.

Is radiotherapy curative for stage I and II low-grade follicular lymphoma? Results of a long-term follow-up study of patients treated at Stanford University.

To evaluate retrospectively the results of radiotherapy for 177 patients with stage I (n = 73 [41%]) and II (n = 104 [59%]) follicular small cleaved-cell and follicular mixed small cleaved-cell and large-cell non-Hodgkin's lymphoma (NHL) treated in the Department of Radiation Oncology, Stanford University between 1961 and 1994. Histology was follicular small cleaved-cell in 101 (57%) cases and follicular mixed small cleaved-cell and large-cell in 76 (43%). Forty-five patients (25%) had staging laparotomy; 34 (19%) had extranodal involvement. All patients had received radiotherapy, either to one side of the diaphragm (involved or extended field) or to both sides (total lymphoid irradiation [TLI] or subtotal lymphoid irradiation [STLI]. Radiotherapy doses ranged from 35 to 50 Gy. The median follow-up duration was 7.7 years. The longest follow-up duration was 31 years. Actuarial survival rates at 5, 10, 15, and 20 years were 82%, 64%, 44%, and 35%, respectively. The median survival time was 13.8 years. At 5, 10, 15, and 20 years, 55%, 44%, 40%, and 37% of patients, respectively, were relapse-free. Only five of 47 patients who reached 10 years without relapse subsequently developed recurrence. Survival and freedom from relapse (FFR) were significantly worse for older patients. Relapse rates were lower following treatment on both sides of the diaphragm or staging laparotomy. Univariate analysis showed that youth and staging laparotomy were associated with significantly better survival and that FFR was better following treatment on both sides of the diaphragm or laparotomy. Radiotherapy remains the treatment of choice for early-stage low-grade follicular lymphomas. Patients who have remained free of disease for 10 years are unlikely to relapse.

Pelvic relapse following subtotal lymphoid irradiation in early stage Hodgkin's disease—An analysis of risk, management, and outcome

To evaluate the time of onset, method of identification, management, and outcome of pelvic relapse following subtotal lymphoid irradiation (STLI) alone (mantle and paraaortic/spleen or splenic pedicle fields, excluding the pelvis) in supradiaphragmatic Stage I-II Hodgkin's disease. A retrospective analysis was performed of the initial, relapse, and regular follow-up evaluations of patients with pelvic relapse following STLI alone from 1968 to the present for supradiaphragmatic Stage I-II Hodgkin's disease after pathologic staging (PS-laparotomy staging) and clinical staging (CS-no laparotomy staging). Following staging, which included bipedal lymphangiography, 482 patients (408 PS and 74 CS), were treated with STLI alone for supradiaphragmatic Stage I-II Hodgkin's disease. The actuarial freedom from relapse at 20 years was 75% in PS patients and 81% in CS patients. The actuarial pelvic failure at 20 years was 7% for PS patients and 3% for CS patients. Of the 29 patients with pelvic relapse, 97% (28 of 29) occurred within 5 years of treatment, including 1 patient who progressed during initial treatment. Pelvic relapse was most commonly initially identified by abnormalities involving patient symptoms (62%), physical examination (55%), erythrocyte sedimentation rate (48%), and bipedal lymphangiogram and/or abdominal radiograph (38%). Relapse was limited to previously unirradiated sites in 17 patients (58%). In addition to pelvic lymph node disease, 3 patients (10%) had involvement of bone, and 4 patients (14%) had bone marrow involvement. Following relapse, all patients were treated with chemotherapy (MOP[P], MOP[P]/ABV[D], ABVD, or PAVe) and 19 of 29 patients received involved field consolidative irradiation. Twenty-one of 29 (72%) remained relapse free at the time of last follow-up evaluation, including 15 of 19 (79%) treated with combined therapy. Eight patients experienced a second relapse despite salvage therapy, and all eight expired with recurrent Hodgkin's disease. Two patients died of complications related to prior treatment. Therefore, the actuarial risk of death at 20 years associated with pelvic failure in the entire cohort of 482 patients was 2%. Pelvic relapse occurred in 7% of patients following STLI alone and was effectively diagnosed by regular follow-up, which included a combination of patient history, physical examination, and radiographic laboratory evaluation. Seventy-two percent of patients remained relapse free following salvage treatment, which included chemotherapy, resulting in an overall survival rate associated with pelvic control of 98%. This approach, therefore, spared the majority of patients the long-term risks associated with pelvic irradiation and/or chemotherapy, such as infertility, but maintained an excellent prognosis.

Radiation-induced premature menopause: A misconception

To disprove the common view that women who have undergone irradiation to fields excluding the pelvis are at risk for radiation-induced premature menopause, we reviewed menstrual function and fertility among women treated with subtotal lymphoid irradiation for Hodgkin's Disease. Treatment and follow-up records of all women less than age 50 at the time of diagnosis of Stage I or II supradiaphragmatic Hodgkin's Disease, treated with subtotal lymphoid irradiation alone and enrolled in radiotherapy trials from 1967 to 1985, were reviewed. In addition, patients were surveyed regarding their menstrual status and fertility history. Thirty-six women, aged 10 to 40 years, with normal menstrual function at the time of Hodgkin's diagnosis, were identified. Mean follow-up was 14 years, with a range of 1.25-22.75 years. The average radiation dose to mantle and paraaortic fields was 40-44 Gy; the calculated scatter radiation dose to the pelvis at the ovaries was 3.2 Gy. There were 38 pregnancies in 18 women; all offspring are normal. One of 36 women (2.7%) experienced premature menopause. The reported rate of premature menopause in women who have not undergone irradiation is 1-3%; not significantly different than the rate in our study. There is a syndrome whereby antibodies to several endocrine organs occur (including the ovary), which is associated with premature ovarian failure. This syndrome may be associated with prior radiation to the thyroid, such as that given by mantle irradiation for Hodgkin's Disease. We report such a case. There is little risk of premature menopause in women treated with radiation fields that exclude the pelvis. Women with presumed radiation-induced premature menopause warrant an evaluation to exclude other causes of ovarian failure, such as autoimmune disorders.

Pelvic relapse following subtotal lymphoid irradiation in early stage Hodgkin's disease-an analysis of risk, management, and outcome

Pelvic relapse following subtotal lymphoid irradiation in early stage Hodgkin's disease-an analysis of risk, management, and outcome

A Case of Severe Aplastic Anemia Transplanted with Allogeneic Bone Marrow Following Premedication by Cyclophosphamide and Subtotal Lymphoid Irradiation

A Case of Severe Aplastic Anemia Transplanted with Allogeneic Bone Marrow Following Premedication by Cyclophosphamide and Subtotal Lymphoid Irradiation

Hodgkin's disease in patients over sixty years old.

Fifty-two patients 60 to 75 years of age were treated for Hodgkin's disease at Stanford University between 1968 and 1980. Adequate staging was defined as including a lymphogram and staging laparotomy for stage I to III and a positive bone marrow or liver biopsy or other evidence of diffuse involvement of extralymphatic tissues for stage IV. Adequate treatment was defined as subtotal lymphoid irradiation for pathologic stages I to IIA; total lymphoid irradiation for stages IIB to IIIA; and chemotherapy with or without irradiation for stages IIIB to IV. Twenty-four patients (46%) had advanced disease (IIIB to IV). Those patients who received appropriate treatment had a median survival of only 39 months. Of the 28 patients with limited disease (I to IIIA), 15 had laparotomy and adequate treatment. Thirteen did not have a laparotomy and 7 were treated with involved-field irradiation. The 5-year survival rate in the laparotomy-staged and adequately treated group was 86%, but in the clinically staged group, only 35% (p = 0.006).