Limited Field Irradiation Research Articles

Long-term outcomes of patients with unfavorable stage I–II classic Hodgkin lymphoma treated with Stanford V chemotherapy and limited field irradiation

Management of stage I–II unfavorable risk Hodgkin lymphoma (HL) strives to reduce toxicity while maintaining tumor control. Compared to ABVD or BEACOPP, Stanford V chemotherapy contains less doxorubicin and bleomycin. We report long-term outcomes of patients with stage I–II classic HL with European risk factors treated with Stanford V combined modality therapy (CMT). From our institutional cancer registry, we identified 168 patients with ≥1 European risk factor treated with 8–12 weeks of Stanford V CMT and consolidative radiotherapy between 1990 and 2016. Outcomes were analyzed after classification by EORTC and GHSG unfavorable criteria. With median follow-up of 8.4 years, 10-year overall survival and progression-free survival for the entire cohort were 95% and 88%, respectively. Thirteen of 18 relapses were salvaged successfully. There were no cases of MDS or AML after primary therapy. Long-term outcomes of stage I–II unfavorable risk HL treated with Stanford V CMT are comparable to ABVD or BEACOPP regimens.

Surgery and Salvage Limited-Field Irradiation for Control of Cutaneous Squamous Cell Carcinoma With Microscopic Residual Disease

This case series analyzes the outcomes of patients with primary cutaneous squamous cell carcinoma treated with limited-field irradiation for microscopic residual disease after surgery.

Longitudinal Effects of Single Hindlimb Radiation Therapy on Bone Strength and Morphology at Local and Contralateral Sites.

Radiation therapy (RTx) is associated with increased risk for late-onset fragility fractures in bone tissue underlying the radiation field. Bone tissue outside the RTx field is often selected as a "normal" comparator tissue in clinical assessment of fragility fracture risk, but the robustness of this comparison is limited by an incomplete understanding of the systemic effects of local radiotherapy. In this study, a mouse model of limited field irradiation was used to quantify longitudinal changes in local (irradiated) and systemic (non-irradiated) femurs with respect to bone density, morphology, and strength. BALB/cJ mice aged 12 weeks underwent unilateral hindlimb irradiation (4 × 5 Gy) or a sham procedure. Femurs were collected at endpoints of 4 days before treatment and at 0, 1, 2, 4, 8, 12, and 26 weeks post-treatment. Irradiated (RTx), Contralateral (non-RTx), and Sham (non-RTx) femurs were imaged by micro-computed tomography and mechanically tested in three-point bending. In both the RTx and Contralateral non-RTx groups, the longer-term (12- to 26-week) outcomes included trabecular resorption, loss of diaphyseal cortical bone, and decreased bending strength. Contralateral femurs generally followed an intermediate response compared with RTx femurs. Change also varied by anatomic compartment; post-RTx loss of trabecular bone was more profound in the metaphyseal than the epiphyseal compartment, and cortical bone thickness decreased at the mid-diaphysis but increased at the metaphysis. These data demonstrate that changes in bone quantity, density, and architecture occur both locally and systemically after limited field irradiation and vary by anatomic compartment. Furthermore, the severity and persistence of systemic bone damage after limited field irradiation suggest selection of control tissues for assessment of fracture risk or changes in bone density after radiotherapy may be challenging. © 2017 American Society for Bone and Mineral Research.

Parathyroid hormone attenuates radiation-induced increases in collagen crosslink ratio at periosteal surfaces of mouse tibia

As part of our ongoing efforts to understand underlying mechanisms contributing to radiation-associated bone fragility and to identify possible treatments, we evaluated the longitudinal effects of parathyroid hormone (PTH) treatment on bone quality in a murine model of limited field irradiation. We hypothesized PTH would mitigate radiation-induced changes in the chemical composition and structure of bone, as measured by microscope-based Raman spectroscopy. We further hypothesized that collagen crosslinking would be especially responsive to PTH treatment. Raman spectroscopy was performed on retrieved tibiae (6–7/group/time point) to quantify metrics associated with bone quality, including: mineral-to-matrix ratio, carbonate-to-phosphate ratio, mineral crystallinity, collagen crosslink (trivalent:divalent) ratio, and the mineral and matrix depolarization ratios. Irradiation disrupted the molecular structure and orientation of bone collagen, as evidenced by a higher collagen crosslink ratio and lower matrix depolarization ratio (vs. non-irradiated control bones), persisting until 12weeks post-irradiation. Radiation transiently affected the mineral phase, as evidenced by increased mineral crystallinity and mineral-to-matrix ratio at 4weeks compared to controls. Radiation decreased bone mineral depolarization ratios through 12weeks, indicating increased mineral alignment. PTH treatment partially attenuated radiation-induced increases in collagen crosslink ratio, but did not restore collagen or mineral alignment. These post-radiation matrix changes are consistent with our previous studies of radiation damage to bone, and suggest that the initial radiation damage to bone matrix has extensive effects on the quality of tissue deposited thereafter. In addition to maintaining bone quality, preventing initial radiation damage to the bone matrix (i.e. crosslink ratio, matrix orientation) may be critical to preventing late-onset fragility fractures.

Long-term loss of osteoclasts and unopposed cortical mineral apposition following limited field irradiation.

Late-onset fragility fractures are a common complication following radiotherapy for metastatic disease and soft tissue sarcomas. Using a murine hindlimb focal irradiation model (RTx), we quantified time-dependent changes in osteoclasts and mineral apposition rate (MAR). Mice received either a single, unilateral 5 Gy exposure or four fractionated doses (4 × 5 Gy). Osteoclast numbers and MAR were evaluated histologically at 1, 2, 4, 8, 12, and 26 weeks post-RTx. Radiation induced an early, transient increase in osteoclasts followed by long-term depletion. Increased osteoclast numbers correlated temporally with trabecular resorption; the resorbed trabeculae were not later restored. Radiotherapy did not attenuate MAR at any time point. A transient, early increase in MAR was noted in both RTx groups, however, the 4 × 5 Gy group exhibited an unexpected spike in MAR eight weeks. Persistent depletion of osteoclasts permitted anabolic activity to continue unopposed, resulting in cortical thickening. These biological responses likely contribute to post-radiotherapy bone fragility via microdamage accumulation and matrix embrittlement in the absence of osteoclastic remodeling, and trabecular resorption-induced decrease in bone strength. The temporal distribution of osteoclast numbers suggests that anti-resorptive therapies may be of clinical benefit only if started prior to radiotherapy and continued through the following period of increased osteoclastic remodeling.

Phase I Trial of Gemcitabine Dose Escalation with Concurrent Radiotherapy for Patients with Locally Advanced Pancreatic Cancer

Aim: The safety and efficacy, and the dose-limiting toxicity (DLT) of the chemotherapeutic agent gemcitabine administered in conjunction with radiotherapy in patients with locally advanced pancreatic cancer are not yet established. Here, we evaluated the safety and efficacy, DLT, and maximum tolerated dose of gemcitabine with concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Tumor response and time to progression were also assessed. Patients and Methods: Patients with previously untreated pancreatic cancer (n = 12) received gemcitabine intravenously on days 1, 8, and 15. Concurrent radiation therapy was initiated on day 1 (40 Gy in 2 Gy/day × 20 fractions, days 1–5, 8–12, 15–19, 22–26). Patients received limited-field irradiation with three-dimensional radiotherapy. Dose escalation included dose levels 1–3 (gemcitabine 400, 600, and 800 mg/m2). Results: No patient developed DLT in this study. Of the 12 patients, there were 11 sustained responses, 0 partial responses, and 1 progressive disease. Two patients with a sustained response underwent surgery after re-evaluation. The median progression-free survival was 8 months, not including the patients that underwent surgery. Conclusion: Weekly gemcitabine at a dose of 800 mg/m2 with concurrent radiation therapy in patients with locally advanced pancreatic cancer was well tolerated.

A multicenter randomized phase II study of full-dose gemcitabine and concurrent radiotherapy comparing gemcitabine alone for the unresectable locally advanced pancreatic adenocarcinoma

e15512 Background: Some of locally advanced pancreatic cancers (LAPC) are considered to include a potential micro metastasis. We think that full-dose of gemcitabine (GEM) improve the outcome of LAPC. We report the efficacy of full-dose GEM and concurrent radiotherapy, comparing GEM alone for unresectable LAPC. Methods: Patients with histologically or cytologically proven pancreatic adenocarcinoma were eligible for this study. We decide that LAPA which involved a major artery with CT imaging was unresectable. Patients were randomized into a concurrent chemoradiotherapy (CRT) group and a chemotherapy alone (CTX) group. GEM was given intravenously at a dose of 1,000 mg/msq over 30 min on days 1, 8 and 15 of each 28-day cycle and repeated until disease progression in both groups. Patients randomized into CRT group received a limited field irradiation with a total dose of 50 Gy in 25 sessions during first two cycles. The two groups were compared for mean survival, progression free survival and safety. Results: From September 2002 to April 2005, 80 patients were randomized at two institutions into the two arms of the trial (40 patients to CRT group and 40 patients to CTX group). The CRT group had better results than the CTX group as measured by mean survival time (391 vs 372 days, P< 0.02) and progression free survival (237 vs 128 days, P< 0.01). There were no differences in the safety between both groups. Conclusions: The concurrent chemoradiotherapy with full-dose GEM is effective and feasible in patients of LAPC compared with full-dose GEM alone. No significant financial relationships to disclose.

Efficacy and toxicity of limited field concurrent chemoradiotherapy (CRT) with capecitabine for locally advanced pancreatic cancer (LAPC)

15586 Background: Treatment outcome in LAPC remains poor. As treatment-related toxicity limits CRT dose-intensification, we evaluated the efficacy/toxicity of capecitabine based CRT in LAPC patients using limited field irradiation, excluding elective nodal areas. Methods: 25 consecutive LAPC patients eligible for CRT were treated at a single institute. Capecitabine was administered at 500–600 mg/m2/b.i.d continuously (including weekends) from day one to completion of radiotherapy (RT). RT was delivered conformally to a dose of 50.4Gy in 28 fractions over 5.5 weeks. The gross tumour volume consisting of the pancreatic tumour and any involved peri-pancreatic nodes was isometrically expanded by 0.5 cm to generate the clinical target volume (CTV). The planning target volume (PTV) comprised the CTV plus a 1cm margin AP/LR and a 1.5 - 2 cm margin SI. Patients were reviewed weekly to monitor weight and collect toxicity data. Time to disease progression and survival were calculated from diagnosis. Results: Median age of the 25 patients (17 M; 8 F) was 66 years (range 45- 74). Tumour was located in the pancreatic head in 23 patients (92%) and histology available in 17 patients (68%). The median (range) PTV volume was 378 (146–860) cc. 2 patients did not complete treatment due to disease progression and post-surgical complication. Treatment was well tolerated with nausea and fatigue being the most common toxicities. Only one patient developed any grade 3 toxicity (nausea). With a median follow up of 8.3 months, the median time to progression was 9.7 months, with 25% remaining progression-free at 1 year. All patients had progressed by 2 years. Isolated loco-regional relapse was observed in only one patient. At progression, six patients were suitable for palliative chemotherapy. The median overall survival for all patients was 11.6 months with 1 year survival of 38%. Median survival for the 6 patients who received palliative chemotherapy at disease progression was 17 months. Conclusion: Limited field CRT using capecitabine 500–600 mg/m2 twice daily in LAPC is very well tolerated, with similar efficacy to historical CRT regimens. Avoiding elective nodal irradiation may allow CRT dose-intensification and combination with other anti-cancer agents. No significant financial relationships to disclose.

Risk Factors and Outcome after Second HLA-Matched Sibling Donor Transplantation for Graft Failure after a First HLA-Matched Sibling Transplant in Severe Aplastic Anemia.

Graft failure rates after HLA matched sibling bone marrow (BM) transplants for severe aplastic anemia (SAA) are about 10%. We analyzed factors that may affect rates of hematopoietic recovery, graft-versus-host (GVHD) and overall survival after a second HLA-matched sibling donor transplant in 166 patients with SAA with graft failure after a first HLA-matched sibling donor transplant. Transplantations occurred between 1986 and 2004; median follow up of surviving patients is 8 years. One hundred and forty patients (84%) received their second transplant for secondary graft failure and 26 (16%), for primary graft failure. The median age at second transplantation was 17 years; 90% of patients were younger than 30 years. Sixty-seven percent had performance scores <90%. All patients received T-replete BM grafts for their first transplant; 16% received peripheral blood progenitor cells and 84% BM for their second transplant. Most (88%) second transplants used the original donor. Median time between first and second transplants was 7 months (range 1 – 114). Seventy-four percent received cyclophosphamide (CY) with or without anti-thymocyte globulin (ATG) conditioning for their first transplant. Forty-nine percent received this regimen for second transplant, 19% received CY and limited field irradiation, 10%, busulfan and CY, 11% melphalan and ATG, 4% other combinations of CY and 7% did not receive a second conditioning regimen. For both transplants, most patients (>95%) received GVHD prophylaxis regimen that included a calcineurin-inhibitor. Probabilities of neutrophil recovery at day 28 and platelet recovery at day 60 after second transplantation were 63% and, 62%. Rates of acute grades 2–4 GVHD at day 100 and chronic GVHD at 5 years were 9% and 16%, respectively. Early mortality rates were high, 30% at day-100. Risks of early mortality were lower when pre-transplant performance scores were 90–100% (relative risk [RR] 0.17, 95% CI 0.06–0.47, p=0.001) and when second transplant occurred >3 months from first transplant (RR 0.32, 95% CI 0.15–0.68, p=0.003). Similarly, risks of overall mortality were lower in patients with performance scores 90 – 100% (RR 0.53, 95% CI 0.30–0.95, p=0.033) and when second transplant occurred >3 months from first transplant (RR 0.47, 95% CI 0.29–0.76, p=0.002). Of the 47 patients who received their second transplant ≤ 3 months after their first transplant, 22 had primary graft failure after their first transplant and 25, early secondary graft failure. Fifteen of these 47 patients failed to achieve neutrophil recovery after their second transplant; 12 of 15 had primary graft failure after first transplant. Other factors such as use of a different donor, conditioning regimen, graft type and growth factor administration did not affect outcome after second transplantation. The 5-year probabilities of overall survival in patients with performance scores 90–100% whose second transplants occurred ≤ 3 months and >3 months after their first transplant were 56% and 76%, respectively. Corresponding rates for patients with performance scores <90 were 33% and 61%. We conclude that salvage with second transplantation after primary or early secondary graft failure is suboptimal. Better therapies are required to ensure sustained hematopoietic recovery in these patients.

Limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer

The outcome of limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer (NSCLC) was analyzed to discuss the elective irradiation of regional lymph nodes. From 1976 through 1994, 36 patients with peripheral stage I NSCLC were treated with definitive radiation therapy (RT) alone at Gunma University hospital. The total dose ranged from 60 to 81 Gy with a 2 Gy-daily standard fractionation, although only one patient received 48 Gy. Ten patients received elective irradiation of the regional lymph nodes with a total dose of 40 Gy or more. The overall response rate was 97% with 31% complete responses. The overall survival rates at 3 and 5 years were 42 and 23%, and disease-specific survival rates were 56 and 39% at 3 and 5 years, respectively. In 26 patients without the elective regional irradiation, disease-specific survival rates at 3 and 5 years were 53 and 40%, respectively, whereas they were 64 and 39% in 10 patients with the regional nodal irradiation. The cumulative 5-year local progression rate was 28%, and the overall progression rate was 60% at 5 years. Four patients had a local recurrence as the only site of initial tumor progression. Combined local and regional progression was seen in two patients, and one patient had a local recurrence in combination with distant metastasis. Twelve patients had distant failure without evidence of local or regional progression. Only one patient without regional nodal irradiation developed an isolated regional failure. No patient had serious complications related to RT. High-dose limited field RT is justified for medically inoperable patients with peripheral stage I NSCLC. The regional nodal irradiation can be omitted in these pulmonary compromised patients because of the low regional relapse rate. Dose-escalation by a conformal RT with a small target volume can be expected to provide a better local control rate and better survival.

Rationale for high-dose cyclophosphamide and medium-dose total body irradiation in the conditioning of children with progressive systemic and polyarticular juvenile chronic arthritis before autologous stem cell transplantation.

Despite the fact that the aetiology of juvenile chronic arthritis (JCA) is unknown, there is ample indirect evidence of a pivotal role of T cells in the onset and probably also in the maintenance of this autoimmune disease. Notwithstanding adequate firstand second-line anti-rheumatic therapy, systemic-onset JCA and polyarticular JCA will lead to destructive arthritis, growth retardation and severe invalidity in 10–25% of the cases. In order to halt the disease progression in the latter group of JCA patients, a clinical trial was started in F. 1. Autologous T-cell-depleted BMT of JCA patients. order to study the effect of severe immune suppression followed by ‘unbiased’ immune recovery on the course of the disease. Based on animal studies, showing the immunity severely, but is supposed not to be myeloregression of adjuvant-induced arthritis by bone marrow ablative. The short-term effect may be the occurrence transplantation (BMT), both allogeneic and T-cellof viral infections or reactivations, especially with herpes depleted autologous BMT [1, 2], a study protocol for viruses. The possible long-term side-effects may be a autologous stem cell transplantation in children with slightly increased risk for premature cataract formation severe progressive systemic and polyarticular JCA was and some effect on spermatogenesis in boys. Our experidrafted. ence so far with this pre-treatment in eight children, There are two conditions which have to be fulfilled in who received an allogeneic BMT for severe aplastic order for autologous stem cell transplantation to posanaemia, four of whom were prepubertal at BMT and sibly be effective in the treatment of JCA, i.e. first, the reached final height at evaluation [3], is as follows: no conditioning has to wipe out the (dysfunctioning) adverse effect has been observed on physical growth, all immunological memory and, second, the re-infused graft recipients had a normal pubertal development, but haematopoietic stem cell suspension has to be purged the boys had a somewhat decreased testicular volume, of mature ‘memory’ T cells. In order to achieve these indicating germ cell damage. Both the boys and the girls goals, the following procedure has been proposed: a showed normal function of the gonads and thyroid pre-treatment regimen comparable to the one in use for gland by endocrinological testing on follow-up. It is still allogeneic BMT of transfusion-sensitized patients with too early to assess fathering/mothering possibilities in severe aplastic anaemia (frequently also an autoimmune this group of ex-BMT recipients. A slight increase in disease), followed by the re-infusion of a T-cell-depleted secondary malignancies has to be expected, as was also (TCD) autologous BMT, i.e. containing ∏104 T cells/kg seen after immunosuppression or allogeneic BMT for body weight of the recipient (see the scheme in Fig. 1). severe aplastic anaemia [4]. Although the use of radiSuch a conditioning suppresses host memory T-cell ation, mostly limited-field irradiation such as total lymphoid irradiation or thoracoabdominal irradiation, was found in that retrospective study to be a strong risk Accepted 15 March 1999.

Bone marrow transplantation for transfused patients with severe aplastic anemia using cyclophosphamide and total lymphoid irradiation as conditioning therapy: long-term follow-up from a single center.

In transfused patients with aplastic anemia, incidence of graft rejection remains significant. Seventeen transfused patients with severe aplastic anemia received BMT from HLA-identical sibling donors after conditioning with cyclophosphamide (CY, 50 mg/kg/day for 4 days) plus total lymphoid irradiation (TLI, 750 cGy in a single dose). For graft-versus-host disease (GVHD) prophylaxis one patient received methotrexate, five patients received CsA and 11 received CsA in association with methylprednisolone. All patients had sustained engraftment. The actuarial survival of patients was 76% with a median follow-up for surviving patients of 11 years (range 0.3-14.5 years). The incidence of grade II-III acute GVHD was 24%, and chronic GVHD 35%. Median Karnofsky score of surviving patients is 100 (range 90-100). Only one patient developed interstitial pneumonia. None of the patients has developed a malignancy after BMT. The role of limited field irradiation in development of malignant neoplasms after BMT for aplastic anemia is discussed. We conclude that a conditioning regimen using CY + TLI in sensitized aplastic anemia patients results in a high survival rate on long-term follow-up.

AIDS-related central nervous system lymphomas.

To evaluate combined radio-chemotherapy in patients with AIDS-related lymphomatous meningitis (LM) or primary central nervous system lymphoma (PCNSL). Eighteen men and 2 women with AIDS had cytologically documented LM. Fifteen patients had systemic non-Hodgkin's lymphoma with LM and 5 patients had PCNSL with CSF dissemination. Standardized pre-treatment evaluations included contrast cranial MRI, placement of an intraventricular reservoir, contrast spine MRI, ophthalmologic evaluation and 111Indium-DTPA CSF flow studies. Regions of bulky or symptomatic disease were treated with limited-field irradiation. Concurrent systemic chemotherapy was administered in 18 patients. All patients were scheduled to receive intraventricular methotrexate (MTX) according to a concentration x time (C x T) drug schedule. In cytologic or clinical failures, patients were treated with salvage therapy using intraventricular ara-C and in a similar manner, patients were treated with intraventricular thio-TEPA following cytologic relapse or clinical failure intraventricular following intraventricular ara-C. Sixty-seven patients (63 men; 4 women) with PCNSL underwent a standardized pre-treatment evaluation as in patients with LM and were treated according to 3 schedules. In the first group (n = 15), comfort care was offered. In the second group (n = 45), whole brain radiotherapy was administered. In the third group (n = 7), patients were treated with combined radio- and chemotherapy using systemic procarbazine, CCNU and vincristine (PCV-3). The third group was selected based on a Karnofsky performance status > or =60, no evidence of disseminated PCNSL, a CD4 count >200, no concurrent opportunistic infection and a patient's desire for aggressive therapy. In the LM patient group, 16 patients were evaluable as 4 patients subsequently withdrew consent for treatment. Median time to tumor progression/survival were as follows: not-treated (n = 4) 12 days/ month; treated non-responding (n = 6) 30 days/2 months; and treated responding (n = 10) 130 days/6 months. In the PCNSL patient group, median range survival were as follows: comfort care (n = 15) 1.5/0.5-3 months; whole brain radiotherapy (n = 45) 4/1.5-5 months; and combined radio-chemotherapy (n = 7) 13/10-18 months. Combined radio- and chemotherapy is appropriate for a small subset of patients with AIDS and either LM or PCNSL. This approach results in meaningful palliation not strikingly dissimilar from that seen in non-AIDS patients.

Limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer

The outcome of limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer (NSCLC) was analyzed to discuss the elective irradiation of regional lymph nodes. From 1976 through 1994, 36 patients with peripheral stage I NSCLC were treated with definitive radiation therapy (RT) alone at Gunma University hospital. The total dose ranged from 60 to 81 Gy with a 2 Gy-daily standard fractionation, although only one patient received 48 Gy. Ten patients received elective irradiation of the regional lymph nodes with a total dose of 40 Gy or more. The overall response rate was 97% with 31% complete responses. The overall survival rates at 3 and 5 years were 42 and 23%, and disease-specific survival rates were 56 and 39% at 3 and 5 years, respectively. In 26 patients without the elective regional irradiation, disease-specific survival rates at 3 and 5 years were 53 and 40%, respectively, whereas they were 64 and 39% in 10 patients with the regional nodal irradiation. The cumulative 5-year local progression rate was 28%, and the overall progression rate was 60% at 5 years. Four patients had a local recurrence as the only site of initial tumor progression. Combined local and regional progression was seen in two patients, and one patient had a local recurrence in combination with distant metastasis. Twelve patients had distant failure without evidence of local or regional progression. Only one patient without regional nodal irradiation developed an isolated regional failure. No patient had serious complications related to RT. High-dose limited field RT is justified for medically inoperable patients with peripheral stage I NSCLC. The regional nodal irradiation can be omitted in these pulmonary compromised patients because of the low regional relapse rate. Dose-escalation by a conformal RT with a small target volume can be expected to provide a better local control rate and better survival. © 1999 Elsevier Science Ireland Ltd. All rights reserved.

Limited field irradiation in early stage (T1-2N0) non-small cell lung cancer

Limited field irradiation in early stage (T1-2N0) non-small cell lung cancer

7a Management of early stage Hodgkin's disease: the role of radiation therapy and/or chemotherapy

The treatment of early stage HD has become more complicated over the past 10 years. The development of standards for both radiation therapy and chemotherapy have made it more feasible to treat HD in community practice settings. Yet initial treatment decisions may have profound long-term effects on patients who are young and likely to have a long survival. Whenever possible, routine cases should be treated along guidelines of standard accepted practice, and physicians should refer patients to major centres for the management of more complicated cases. There is hope that less toxic chemotherapy will be effective in curing occult microscopic disease, perhaps eventually obviating the need for staging laparotomy and splenectomy. Yet for now, there are little long-term data defining specifics of treatment, or the long-term efficacy or toxicity of modified regimens. Thus at present, the management of patients with HD in ways that do not adhere to standard practice, such as modifying standard RT or chemotherapy, should be strongly discouraged outside controlled clinical trials. In parts of the USA there is still a general acceptance of staging laparotomy and splenectomy as a means to aggressively stage patients in order to minimize treatment. By utilizing diagnostic laparotomy and splenectomy, the majority of patients with PS IA-IIA HD will be cured with RT alone thus sparing them the toxicity of combined chemotherapy and RT, and preserving the effectiveness of chemotherapy in case of relapse. Using this approach, patients who are likely to need chemotherapy due to a high risk of relapse (LMA, or extensive B symptoms), or high risk for having abdominal involvement (more than one positive abdominal radiographical test) should not undergo a staging laparotomy. In addition, chemotherapy and limited field irradiation may be preferred under special circumstances (i.e. for paediatric patients). Diagnostic staging laparotomy and splenectomy is not routinely performed outside the continental USA. Academic centres in Canada, Europe and South America have identified prognostic factors to aid in determining treatment for clinically staged patients. Patients with the most favourable characteristics receive RT alone with CMT used for the remainder of patients. On average, without the information obtained at staging laparotomy, patients require more treatment, either with larger radiation fields, or with the more frequent use of chemotherapy.

Limited field irradiation in early stage (T 1–2N 0) non-small cell lung cancer

Background and purpose: Radiotherapy can effectively control non-small cell lung cancers (NSCLC) of limited size. This study is conducted to investigate whether limited field irradiation, without irradiation of regional lymph nodes, can safely be used in these patients. Materials and methods: Between 1988 and 1993, 31 patients with operable T 1–2N 0 NSCLC received radiotherapy (48 Gy in 12 fractions) to a limited (‘postage stamp’) field. The hilum and mediastinum were not included in the radiation portals. Results: Overall survival was 42% at 3 years. Disease-specific survival at 3 years was 76%. One patient developed an isolated regional failure, one had a combined local and distant failure, one had a combined local, regional and distant failure, while three patients failed at distant sites only. Thus, only two patients (6%) recurred regionally. Conclusions: This study shows that ‘postage stamp’ irradiation is an effective alternative to surgery. Radiation of the hilar and mediastinal lymph nodes can be omitted in these pulmonary compromised patients.

Bone Marrow Transplantation for Fanconi Anemia

Abstract Fanconi anemia is a genetic disorder associated with diverse congenital abnormalities, progressive bone marrow failure, and increased risk of leukemia and other cancers. Affected persons often die before 30 years of age. Bone marrow transplantation is an effective treatment, but there are few data regarding factors associated with transplant outcome. We analyzed outcomes of HLA-identical sibling (N = 151) or alternative related or unrelated donor (N = 48) bone marrow transplants for Fanconi anemia performed between 1978 and 1994 and reported to the International Bone Marrow Transplant Registry. Fanconi anemia was documented by cytogenetic studies in all cases. Patient, disease, and treatment factors associated with survival were determined using Cox proportional hazards regression. Two-year probabilities (95% confidence interval) of survival were 66% (58% to 73%) after HLA-identical siblings transplants and 29% (18% to 43%) after alternative donor transplants. Younger patient age (P .0001), higher pretransplant platelet counts (P = .04), use of antithymocyte globulin (P = .005), and use of low-dose (15 to 25 mg/kg) cyclophosphamide plus limited field irradiation (P = .009) for pretransplant conditioning and cyclosporine for graft-versus-host disease prophylaxis (P = .002) were associated with increased survival. Bone marrow transplants are effective therapy for Fanconi anemia. The adverse impact of increasing age and lower pretransplant platelet count on transplant outcome favors earlier intervention, especially when there is an HLA-identical sibling donor.

Bone marrow transplantation for Fanconi anemia

Fanconi anemia is a genetic disorder associated with diverse congenital abnormalities, progressive bone marrow failure, and increased risk of leukemia and other cancers. Affected persons often die before 30 years of age. Bone marrow transplantation is an effective treatment, but there are few data regarding factors associated with transplant outcome. We analyzed outcomes of HLA-identical sibling (N = 151) or alternative related or unrelated donor (N = 48) bone marrow transplants for Fanconi anemia performed between 1978 and 1994 and reported to the International Bone Marrow Transplant Registry. Fanconi anemia was documented by cytogenetic studies in all cases. Patient, disease, and treatment factors associated with survival were determined using Cox proportional hazards regression. Two-year probabilities (95% confidence interval) of survival were 66% (58% to 73%) after HLA-identical siblings transplants and 29% (18% to 43%) after alternative donor transplants. Younger patient age (P .0001), higher pretransplant platelet counts (P = .04), use of antithymocyte globulin (P = .005), and use of low-dose (15 to 25 mg/kg) cyclophosphamide plus limited field irradiation (P = .009) for pretransplant conditioning and cyclosporine for graft-versus-host disease prophylaxis (P = .002) were associated with increased survival. Bone marrow transplants are effective therapy for Fanconi anemia. The adverse impact of increasing age and lower pretransplant platelet count on transplant outcome favors earlier intervention, especially when there is an HLA-identical sibling donor.

Radiation therapy and bromodeoxyuridine chemotherapy followed by procarbazine, lomustine, and vincristine for the treatment of anaplastic gliomas

Purpose : To conduct a Phase II study to evaluate the long-term efficacy and safety of radiotherapy combined with intravenous bromodeoxyuridine for patients with anaplastic glioma tumors. Methods and Materials : Between 1983 and 1987, study patients received 1.7–1.8 Gy radiation once a day, Monday through Friday, to a toatl dose of 60 Gy. On the Thursday prior to beginning radiotherapy and for the next 5 weeks (6 weeks total), patients received a continuous 96 h intravenous infusion of bromodeoxyuridine at 0.8 g/m 2/24 h; following radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until tumor progressed. Results : One-hundred thirty eight patients (median age, 43 years) were evaluated for analysis. Estimated 4-year survival for the anaplastic astrocytoma (AA) stratum ( n = 116) is 46%. For the astrocytoma (ASTRO) stratum ( n = 22), the 6-year survival is estimated at 79%. Estimated 4-year progression-free survival for AAs is 42%, and for ASTROs, 68%. Whole brain irradiation was used in 23% and limited-field irradiation in 77%; patients receiving limited-field irradiation had a better survival rate ( p = 0.07). Total tumor resection was performed in 15%, partial resection in 53%, and biopsy only in 32%. For the 81 patients with tumor recurrence, 34 (42%) are known to have received additional treatment(s). For AA, fits of the Cox proportional hazards regression model showed that covariates individually predictive of survival were younger age ( p < 0.001), Karnofsky performance score ( p = 0.04), and extent of surgery ( p = 0.04); limited-field irradiation was not significant ( p = 0.10). Major toxicities were rash during Weeks 1 through 6 requiring dose modification in 14%, Garde ≥III leukopenia in 18%, and Grad ≥III thrombocytopeni in 9%. Conclusion : The study suggests that the bromodeoxyuridine-radiotherapy-PCV, compared with other published therapies, can improve progression-free survival, and aggressive treatment of ASTRO patients can lead to substantial increases in survival compared to published survival data.