- Email: [email protected]
907 poster PRIMARY CNS LYMPHOMA (PCNSL): A RETROSPECTIVE ANALYSIS OF PATIENTS TREATED WITH PALLIATIVE RADIOTHERAPY (RT)
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LYMPHOMA
CEA/ABVD regimen (baseline). Bloc-chemotherapy CEA/ABVD regimen was introduced in 2007. Chemotherapy was given weekly for 17 weeks as follows: doxorubicin 25 mg/m2 on weeks 1, 3, 5, 7, 9, 11, 13, 15, and 17; bleomycin 10 mg/m2 (maximum dose, 15 mg) and vinblastine 6 mg/m2 (maximum dose, 10 mg) and dacarbazine 375 mg/m2 on weeks 1, 5, 7, 11, 13, and 17; lomustine 80 mg/m2 and etoposide 100 mg/m2 for three days on weeks 3, 9, and 15. Forty seven patients were treated with bloc-chemotherapy CEA/ABVD regimen. Eight patients were treated with IFRT or INRT, 45 with EFRT, 54 with STNI. Results: After a median observation time of 4.1 years, the rates for freedom from treatment failure (FFTF) are 95.5 percent, and for overall survival (OS) 93.7 percent for regimen CEA/ABVD. There have been no deaths among the 51 patients in groups with early and intermediate prognosis, one relapse has occurred (1.9%). Two relapses and one death (HL) have occurred in the group of 20 patients with stage II bulky mediastinal disease, one relapse and four deaths in the group of 38 patients with stage III-IV disease (1 HL, 1 hematologic toxicity, 2 cardiovascular disease; age>45 years). In grope CEA/ABVD (baseline) with a median follow-up of 6.6 years, 3 of 60 patients were relapse HL, rates for FFTF are 94.7 percent, OS 91.1%. In grope bloc-chemotherapy CEA/ABVD with a median follow-up of 1.9 years, 1 of 47 patients were relapse HL, rates for FFTF are 96.4 percent, OS 100%. In grope with STNI two relapse has occurred (3.7%), with EFRT 2 (4.4%), IFRT or INRT 0%.Acute Toxicity: one death has occurred in the group with CEA/ABVD (baseline) to patient with hematologic toxicity grade 4 (male, 48 year; 1.7%). Myelosuppression constituted the major acute toxicity (107 patients). Thirty three patients had an ANC less than 500/μL (35.5%) and 15 patients had an ANC less than 100/μL (14%) at some time during chemotherapy. In the groups with CEA/ABVD (baseline or bloc) toxicity was tolerable with WHO grade 3/4 leucopenia in 63.3% and 74.4% of chemotherapy cycles, grade IV leucopenia 25% and 44.7%. Grade 3-4 anemias were observed in 13.3% and 25.5%, thrombocytopenia grade 3/4 recorded in 20% and 19.1%. In grope with CEA/ABVD (baseline) G-CSF was routinely used after the initial dose reduction or delay, a total of 25 patients received G-CSF. Dose reduction was a total of 14 patients (23.3%), delay chemotherapy - 2 patients (3.3%), 1/2 course - 7 patients (11.7%). In grope with bloc-chemotherapy CEA/ABVD a total of 33 patients received G-CSF (72.2%). Dose reduction no was in group bloc-chemotherapy CEA/ABVD (0%), dose delay of 7 days - 1 patient (2.3%). Febrile neutropenia in the course of bloc-chemotherapy CEA/ABVD no complicated of combination chemotherapy injections. In contrast, febrile neutropenia (23.3% and 21.9%) were more frequent in CEA/ABVD (baseline). Infection rate was 11.5% (CEA/ABVD (baseline) 11.6%; Bloc-chemotherapy 11.4%), pneumonia (1.7% and 2.3%), and hair loss 100%. In contrast, acute nausea (83.3% and 72.7%), gastrointestinal toxicity (8.3% and 2.3%), and pharyngeal toxicity (5% and 9.1%) were more frequent in CEA/ABVD (baseline). Two patients were hospitalized during or within 3 months of completing CEA/ABVD (baseline) with cardiovascular disease (3.3%), one of them died. One death occurred in the group with CEA/ABVD (baseline) to patient with fatal pneumonitis (1.7%). Late Toxicity: a 31-year-old woman developed non-Hodgkin’s lymphoma orbit through 2.5 year after CEA/ABVD chemotherapy regimen (baseline). A 31-year-old man developed tuberculosis through 2 year after CEA/ABVD chemotherapy regimen (baseline). With a median follow-up of 4.1 years, after CEA/ABVD (107 patients) no cases of a single second malignancy, secondary leukemia, myelodysplasia have been observed to date. Conclusions: These data confirm that CEA/ABVD chemotherapy with RT is highly effective in locally extensive and advanced Hodgkin’s disease. It is most important to compare this approach with standard doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy to determine whether CEA/ABVD with or without RT represents a therapeutic advance. 906 poster OCULAR TOXICITY AFTER 3D-CONFORMAL RADIOTHERAPY FOR NON-HODGKIN ORBITAL LYMPHOMA L. Vinante1 , C. Boso1 , F. Vianello1 , H. El Barbir1 , S. Aversa2 , D. Marino2 , D. Fiore3 , G. Sotti1 1 I STITUTO O NCOLOGICO V ENETO, Department of Radiotherapy and Nuclear Medicine, Padova, Italy 2 I STITUTO O NCOLOGICO V ENETO, Department of Oncology, Padova, Italy 3 U NIVERSITY OF PADUA, Department od Diagnostic Sciences and Special Therapies, Padua, Italy Purpose: The orbital Non-Hodgkin lymphoma (NHL) is a rare malignancy, usually localized and low aggressive, which management requires the irradiation of whole orbital cavity. This involves structures, as lens, particularly sensible to radiation effects. This single institution study wants to evaluate the acute and late side effects of conformal 3D irradiation for primary NHL. Materials: We retrospectively evaluated 59 consecutive patients (20 women and 39 men, mean age 59 ± 16 yrs) with stage IEA NHL from 1986 to 2010. The disease was localized in the left eye in 34 (58%) patients, in the right in 21 (35%), bilateral in 4 (7%), and involved the orbit in 30 (51%), the conjunctiva in 18 (31%) and other orbital structures in 11 (18%). All patients underwent 3D-conformal radiotherapy after diagnosis (by pathological or cytological examination), staging (haematological tests, total body CT, bone marrow biopsy,
orbital CT or MR) and in 4 cases after chemotherapy. The median dose was 30.6 Gy (range 30-40 Gy) with a standard fractioning (1.8 Gy per day) and the PTV consisted of whole orbital cavity. The bolus (thickness 0.5-1 cm) was used only in case of superficial localizations (25%). We described acute and late toxicity incidence and calculated the risk factors for cataract, using chi-square or Fisher test as appropriate. Results: The mean follow up was 68.3 ± 55 months. It was performed by clinical and radiological examinations (total body CT, lymphatic stations US) and by ophthalmic visits, every 46 months during the first 5 years and then once a year. The local control was obtained in 58 (98.3%) patients. According to the RTOG scale, the grade (G) 1 and 2 acute effects were 37% and 24% respectively, no G3-4 were observed in 39%. Thirty-six (61%) patients had no late toxicity, 22(37%) presented low effects (G1-2) and only 1 (2%) had retinopathy and bilateral cataract (G3). The table 1 reports the adverse effects. The cataract developed in 20 (34%) patients 2-7 yrs after radiotherapy was the more common late effect. It was easily treated by surgery. We considered as possible risk factors for cataract: age >60 yrs, Karnofsky performance status < 90%, total dose > 30.6 Gy, use of bolus and chemotherapy association. Total dose > 30.6 Gy resulted significantly associated (p<0.005). Cataract was developed in 13 of 24 patients (54%) treated with dose >30.6 (median 36 Gy), in 7 of 35 (20%) with dose ≤ 30.6.
Conclusions: 3D conformal radiotherapy was effective and well tolerated, with low-grade acute and late toxicity, for patients with orbital lymphoma. Cataract was the more frequent side effect, it was associated with a total dose > 30.6 Gy and easily treated with surgery. Eyesight was well preserved. 907 poster PRIMARY CNS LYMPHOMA (PCNSL): A RETROSPECTIVE ANALYSIS OF PATIENTS TREATED WITH PALLIATIVE RADIOTHERAPY (RT) M. Buglione1 , P. Borghetti1 , F. Trevisan1 , M. Maddalo1 , B. Bonetti1 , L. Bandera1 , L. Triggiani1 , L. Donadoni1 , B. Shehi1 , S. Magrini1 S PEDALI C IVILI DI B RESCIA, Department of Radiation Oncology, Brescia, Italy
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Purpose: The incidence of PCNSL has increased in the last decades, in immuno-compromised as well as in immuno-competent individuals; generally HIV positive patients have a worse prognosis. Nowadays, in a curative setting, the standard treatment of PCNSL is considered systemic chemotherapy with high dose methotrexate (HD-MTX) and Ara-C, with RT given upfront to complete first line treatment. RT can also be considered a less aggressive possibility in the salvage and/or palliative setting. The aim of this study is to retrospectively analyse the clinical and therapeutic features of 64 patients consecutively treated at the Radiation Oncology Department Brescia University between January 1988 and April 2008. Materials: All the clinical, diagnostic and therapeutic features of the 64 cases were collected from the clinical records and analysed after their introduction in a general database. The different clinical and therapeutic features were analysed. Overall survival (OS) was calculated from the end of RT to the last follow-up. "Short" and "long" survivors were defined patients died within 1 and after 6 months from the end of RT, respectively. All statistical analysis were performed with SPSS 17th software. Results: In this series two peaks of accrual were observed: 1993 through 1997 and in the last two years (2006-2008). Most of the patients were immunocompetent (83%). Eleven patients had AIDS. Thirty-eight patients (59%) were aged > 60 years, 28 (44%) had IK <=70 and most of them had different neurological symptoms (95%). The symptoms were often differently combined but the most frequent were cognitive focal deficits in 43% (28 pts), depressed level of consciousness 20 % (13 pts); intracranial hypertension 15% (10 pts). The majority of these pts (61%) had histological confirmation of the diagnosis, the others only an unequivocal radiological diagnosis; 35 patients (54%) had high grade lymphoma. The first site of disease was mainly in the deep structures of the brain (64%). All the patients were treated with RT and 70% with RT alone. RT dose < 30 Gy was used mostly in young (< 60 years), HIV positives and KPS < 70 patients. "Palliative high dose approach" (≥ 30 Gy), older age, KPS ≥ 70, immunecompetency are significantly related with better OS at univariate analysis. Of these factors, RT dose does
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not retain significance at multivariate analysis, but it is associated with better OS when "short" and "long term" survivors are analyzed separately. Overall median survival was 187 days; actuarial OS at 1 and 5 years was 42% and 5% respectively. Conclusions: Age ≥ 60 years, normal immune status, good performance status are confirmed as important prognostic factors. High doses of RT and adherence to prescribed treatment are the most important predictive factors related to RT treatment. RT alone, also hypofractionated, with doses > 46 Gy can be considered in selected patients not eligible for radical treatment. 908 poster RISK OF CARDIAC AND VALVULAR DISEASE AFTER MANTLE OR INVOLVED NODE RADIOTHERAPY IN HODGKIN LYMPHOMA M. Maraldo1 , M. Aznar1 , P. Brodin1 , P. Munck af Rosenschöld1 , P. M. Petersen1 , I. R. Vogelius1 , L. Specht1 2 1 T HE F INSEN C ENTER - R IGSHOSPITALET, Copenhagen, Denmark 2 C OPENHAGEN U NIVERSITY, Faculty of Health Sciences, Copenhagen, Denmark Purpose: The risk of developing cardiac disease (CD) for long-term Hodgkin lymphoma (HL) survivors after mediastinal radiotherapy (RT) is under debate, as current data are, primarily, derived from patients treated with the outdated Mantle Field (MF) technique.In this work, we compare doses to the heart and four heart valves with Involved Node RT (INRT), the present standard of treatment, and MF. We also derive and compare the excess absolute risk (EAR) of developing CD using both techniques. Materials: We included 10 adolescents-young adults with clinical stage I-II HL. All patients were treated with chemotherapy and INRT (30-36 Gy). For each patient we simulated a MF, delivering 36 Gy.We derived a logistic doseresponse function for the 25 year risk of any CD and valvular disease (VD) using published data from a HL cohort[1]. For each patient we estimated the risk of any CD and VD from the individual dose volume histogram and the dose-response function. Results: For all 10 patients the mean heart dose was 4.9 Gy (range: 0.118 Gy) and 24.8 Gy (range: 18.6-28.8) with INRT and MF, respectively. For mean doses to the individual valves see fig. 1.The mean EAR 25 years after treatment was 0.8% (range: 0.4-3.5%) for CD and 0.04% (range: 0-2.46%) for any VD with INRT. For MF the mean EAR was 6.6% (range: 6-10. 1%) for CD and 8% (range: 2.7-14.4%) for any VD.
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909 poster TOTAL MARROW IRRADIATION AS SELECTIVE BOOST MODALITY AFTER CONVENTIONAL TBI FOR PATIENTS WITH ADVANCED HEMOPOIETIC MALIGNANCIES UNDERGOING AN ALLOGENEIC STEM CELL TRANSPLANT. S. Vagge1 , M. Zeverino2 , S. Agostinelli2 , S. Barra1 , F. Frassoni3 , G. Taccini2 , A. Bacigalupo3 , R. Corvò1 1 N ATIONAL I NSTITUTE FOR C ANCER R ESEARCH, Department of Radiation Oncology, Genova, Italy 2 N ATIONAL I NSTITUTE FOR C ANCER R ESEARCH, Medical Physics, Genova, Italy 3 A ZIENDA OSPEDALIERA UNIVERSITARIA S AN M ARTINO, Hematology, Genova, Italy Purpose: To report our clinical experience in planning and delivering Total Marrow Irradiation (TMI) after Total Body Irradiation (TBI) in patients with acute leukemia in relapse status or in second remission undergoing an allogeneic stem cell transplant (SCT). Materials: Patients received conventional TBI as 200 cGy BID/ day for 3 days boosted the next day by TMI (2 Gy in a single fraction) and followed by cyclophosphamide (Cy) 60 mg/ kg for 2 days. While TBI was delivered with linear accelerator, TMI was performed with helical tomotherapy (HT). Results: Seventeen patients were treated from July 2009 till August 2010, eleven with acute myeloid leukemia, five with acute lymphoid leukemia and one with myelodisplasia.. At the time of radiotherapy eight patients were in relapse, eight in second remission and one in third complete remission (CR) after relapse. The donor was a matched sibling in 7 cases, an unrelated donor in11 cases. Median organ-at-risk dose reduction with TMI ranged from 30% to 65% with the largest reduction (-50%-65%) achieved for brain, larynx, liver, lungs and kidneys. Target areas (bone marrow sites and spleen in selected cases) were irradiated with an optimal conformity and an excellent homogeneity. Follow-up ranges from 90 days to 530 days (median 320 days). However, tolerance was not different from a conventional TBI-Cy. All patients treated with TBI/TMI reached CR after SCT. Seven (41%) patients relapsed at median time of 276 days (range: 166- 446 days) . Eight (47%) patients have died, 5 for treatment-related toxicity and 3 for disease relapse. Nine (53%) patients are alive with five survivors in table clinical remission of disease Conclusions: This study confirms the clinical feasibility of using HT to deliver TMI as selective dose boost modality after TBI. Since the rate of relapse remains high after 14 Gy TBI/TMI, a dose escalation trial to determine the maximum tolerated dose of TMI given as multi-step boost irradiation is now starting at our institution for the treatment of patients with relapsed acute leukemia after previous SCT.
Normal tissue 910 poster ASSOCIATION BETWEEN SINGLE NUCLEOTIDE POLYMORPHISMS AND HAPLOTYPES IN THE VEGF GENE AND LATE TOXICITY IN PROSTATE CANCER PATIENTS T. Langsenlehner1 , E. M. Thurner1 , W. Renner1 , G. Hofmann1 , K. Kapp1 , U. Langsenlehner1 1 M EDICAL U NIVERSITY OF G RAZ, Graz, Austria
Fig. 1. The distribution of the mean dose to the whole heart and the four heart valves for our 10 patients for INRT (red) and MF (blue). The boxes represent 25-75% percentile and the whiskers represent the range. Conclusions: Our results show, that the mean dose to the heart and four heart valves was much lower with INRT compared with MF for most patients. However, for a subset of patients, even INRT plans will expose the heart and heart valves to high doses with a 25 year EAR of a cardiac event of up to 3.5%. For such patients the use of even more conformal techniques than INRT, and/or further dose reduction, is needed to minimize the risk of severe long-term complications. References[1] G. Schellong et al. Late valvular and other cardiac diseases after different doses of mediastinal radiotherapy for Hodgkin disease in children and adolescents. Pediatr Blood Cancer 2010;55:1145-1152.
Purpose: Vascular endothelial growth factor (VEGF) plays a key role in the regulation of angiogenesis and vascular permeability and has been shown to be up-regulated during the late phase of radiation injury. The present prospective study was performed to evaluate the association of VEGF single nucleotide polymorphisms (SNPs) and haplotypes with the development of radiation induced late side effects in prostate cancer patients. Materials: To analyze the role of VEGF polymorphisms and haplotypes for high-grade rectal or genitourinary late toxicity (defined as late toxicity RTOG ≥2) 493 prostate cancer patients from the Austrian PROCAGENE study treated with definitive radiotherapy were included in the present investigation. Seven candidate polymorphisms in the VEGF gene were selected and determined by 5-nuclease (TaqMan) assays. Haplotypes and linkage disequilibrium were determined using the Haploview program. Haplotype analysis showed two separate blocks of high-linkage disequilibrium, formed by five polymorphisms (-2578C>A, -2489C>T, -1498C>T, -634G>C, -7C>T) upstream of the coding sequence (promoter and 50-untranslated region) and two polymorphisms (936C>T and 1612G>A) downstream of the coding sequence. Results: Within a median follow-up time of 35 months, 42 patients (8.5%) developed high-grade late rectal toxicity and 47 patients (9.5%) late bladder toxicity. In a KaplanMeier analysis, carriers of the VEGF -7C>T polymorphism were at increased risk of high-grade late rectal toxicity (p= 0.003), in multivariate analysis including clinical and dosimetric parameters as potential confounders the VEGF -7C>T polymorphism remained a significant predictor for high-grade late toxicity (HR= 2.8, 95% CI 1.349 to 5.813; p= 0.006).
LYMPHOMA
CEA/ABVD regimen (baseline). Bloc-chemotherapy CEA/ABVD regimen was introduced in 2007. Chemotherapy was given weekly for 17 weeks as follows: doxorubicin 25 mg/m2 on weeks 1, 3, 5, 7, 9, 11, 13, 15, and 17; bleomycin 10 mg/m2 (maximum dose, 15 mg) and vinblastine 6 mg/m2 (maximum dose, 10 mg) and dacarbazine 375 mg/m2 on weeks 1, 5, 7, 11, 13, and 17; lomustine 80 mg/m2 and etoposide 100 mg/m2 for three days on weeks 3, 9, and 15. Forty seven patients were treated with bloc-chemotherapy CEA/ABVD regimen. Eight patients were treated with IFRT or INRT, 45 with EFRT, 54 with STNI. Results: After a median observation time of 4.1 years, the rates for freedom from treatment failure (FFTF) are 95.5 percent, and for overall survival (OS) 93.7 percent for regimen CEA/ABVD. There have been no deaths among the 51 patients in groups with early and intermediate prognosis, one relapse has occurred (1.9%). Two relapses and one death (HL) have occurred in the group of 20 patients with stage II bulky mediastinal disease, one relapse and four deaths in the group of 38 patients with stage III-IV disease (1 HL, 1 hematologic toxicity, 2 cardiovascular disease; age>45 years). In grope CEA/ABVD (baseline) with a median follow-up of 6.6 years, 3 of 60 patients were relapse HL, rates for FFTF are 94.7 percent, OS 91.1%. In grope bloc-chemotherapy CEA/ABVD with a median follow-up of 1.9 years, 1 of 47 patients were relapse HL, rates for FFTF are 96.4 percent, OS 100%. In grope with STNI two relapse has occurred (3.7%), with EFRT 2 (4.4%), IFRT or INRT 0%.Acute Toxicity: one death has occurred in the group with CEA/ABVD (baseline) to patient with hematologic toxicity grade 4 (male, 48 year; 1.7%). Myelosuppression constituted the major acute toxicity (107 patients). Thirty three patients had an ANC less than 500/μL (35.5%) and 15 patients had an ANC less than 100/μL (14%) at some time during chemotherapy. In the groups with CEA/ABVD (baseline or bloc) toxicity was tolerable with WHO grade 3/4 leucopenia in 63.3% and 74.4% of chemotherapy cycles, grade IV leucopenia 25% and 44.7%. Grade 3-4 anemias were observed in 13.3% and 25.5%, thrombocytopenia grade 3/4 recorded in 20% and 19.1%. In grope with CEA/ABVD (baseline) G-CSF was routinely used after the initial dose reduction or delay, a total of 25 patients received G-CSF. Dose reduction was a total of 14 patients (23.3%), delay chemotherapy - 2 patients (3.3%), 1/2 course - 7 patients (11.7%). In grope with bloc-chemotherapy CEA/ABVD a total of 33 patients received G-CSF (72.2%). Dose reduction no was in group bloc-chemotherapy CEA/ABVD (0%), dose delay of 7 days - 1 patient (2.3%). Febrile neutropenia in the course of bloc-chemotherapy CEA/ABVD no complicated of combination chemotherapy injections. In contrast, febrile neutropenia (23.3% and 21.9%) were more frequent in CEA/ABVD (baseline). Infection rate was 11.5% (CEA/ABVD (baseline) 11.6%; Bloc-chemotherapy 11.4%), pneumonia (1.7% and 2.3%), and hair loss 100%. In contrast, acute nausea (83.3% and 72.7%), gastrointestinal toxicity (8.3% and 2.3%), and pharyngeal toxicity (5% and 9.1%) were more frequent in CEA/ABVD (baseline). Two patients were hospitalized during or within 3 months of completing CEA/ABVD (baseline) with cardiovascular disease (3.3%), one of them died. One death occurred in the group with CEA/ABVD (baseline) to patient with fatal pneumonitis (1.7%). Late Toxicity: a 31-year-old woman developed non-Hodgkin’s lymphoma orbit through 2.5 year after CEA/ABVD chemotherapy regimen (baseline). A 31-year-old man developed tuberculosis through 2 year after CEA/ABVD chemotherapy regimen (baseline). With a median follow-up of 4.1 years, after CEA/ABVD (107 patients) no cases of a single second malignancy, secondary leukemia, myelodysplasia have been observed to date. Conclusions: These data confirm that CEA/ABVD chemotherapy with RT is highly effective in locally extensive and advanced Hodgkin’s disease. It is most important to compare this approach with standard doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy to determine whether CEA/ABVD with or without RT represents a therapeutic advance. 906 poster OCULAR TOXICITY AFTER 3D-CONFORMAL RADIOTHERAPY FOR NON-HODGKIN ORBITAL LYMPHOMA L. Vinante1 , C. Boso1 , F. Vianello1 , H. El Barbir1 , S. Aversa2 , D. Marino2 , D. Fiore3 , G. Sotti1 1 I STITUTO O NCOLOGICO V ENETO, Department of Radiotherapy and Nuclear Medicine, Padova, Italy 2 I STITUTO O NCOLOGICO V ENETO, Department of Oncology, Padova, Italy 3 U NIVERSITY OF PADUA, Department od Diagnostic Sciences and Special Therapies, Padua, Italy Purpose: The orbital Non-Hodgkin lymphoma (NHL) is a rare malignancy, usually localized and low aggressive, which management requires the irradiation of whole orbital cavity. This involves structures, as lens, particularly sensible to radiation effects. This single institution study wants to evaluate the acute and late side effects of conformal 3D irradiation for primary NHL. Materials: We retrospectively evaluated 59 consecutive patients (20 women and 39 men, mean age 59 ± 16 yrs) with stage IEA NHL from 1986 to 2010. The disease was localized in the left eye in 34 (58%) patients, in the right in 21 (35%), bilateral in 4 (7%), and involved the orbit in 30 (51%), the conjunctiva in 18 (31%) and other orbital structures in 11 (18%). All patients underwent 3D-conformal radiotherapy after diagnosis (by pathological or cytological examination), staging (haematological tests, total body CT, bone marrow biopsy,
orbital CT or MR) and in 4 cases after chemotherapy. The median dose was 30.6 Gy (range 30-40 Gy) with a standard fractioning (1.8 Gy per day) and the PTV consisted of whole orbital cavity. The bolus (thickness 0.5-1 cm) was used only in case of superficial localizations (25%). We described acute and late toxicity incidence and calculated the risk factors for cataract, using chi-square or Fisher test as appropriate. Results: The mean follow up was 68.3 ± 55 months. It was performed by clinical and radiological examinations (total body CT, lymphatic stations US) and by ophthalmic visits, every 46 months during the first 5 years and then once a year. The local control was obtained in 58 (98.3%) patients. According to the RTOG scale, the grade (G) 1 and 2 acute effects were 37% and 24% respectively, no G3-4 were observed in 39%. Thirty-six (61%) patients had no late toxicity, 22(37%) presented low effects (G1-2) and only 1 (2%) had retinopathy and bilateral cataract (G3). The table 1 reports the adverse effects. The cataract developed in 20 (34%) patients 2-7 yrs after radiotherapy was the more common late effect. It was easily treated by surgery. We considered as possible risk factors for cataract: age >60 yrs, Karnofsky performance status < 90%, total dose > 30.6 Gy, use of bolus and chemotherapy association. Total dose > 30.6 Gy resulted significantly associated (p<0.005). Cataract was developed in 13 of 24 patients (54%) treated with dose >30.6 (median 36 Gy), in 7 of 35 (20%) with dose ≤ 30.6.
Conclusions: 3D conformal radiotherapy was effective and well tolerated, with low-grade acute and late toxicity, for patients with orbital lymphoma. Cataract was the more frequent side effect, it was associated with a total dose > 30.6 Gy and easily treated with surgery. Eyesight was well preserved. 907 poster PRIMARY CNS LYMPHOMA (PCNSL): A RETROSPECTIVE ANALYSIS OF PATIENTS TREATED WITH PALLIATIVE RADIOTHERAPY (RT) M. Buglione1 , P. Borghetti1 , F. Trevisan1 , M. Maddalo1 , B. Bonetti1 , L. Bandera1 , L. Triggiani1 , L. Donadoni1 , B. Shehi1 , S. Magrini1 S PEDALI C IVILI DI B RESCIA, Department of Radiation Oncology, Brescia, Italy
1
Purpose: The incidence of PCNSL has increased in the last decades, in immuno-compromised as well as in immuno-competent individuals; generally HIV positive patients have a worse prognosis. Nowadays, in a curative setting, the standard treatment of PCNSL is considered systemic chemotherapy with high dose methotrexate (HD-MTX) and Ara-C, with RT given upfront to complete first line treatment. RT can also be considered a less aggressive possibility in the salvage and/or palliative setting. The aim of this study is to retrospectively analyse the clinical and therapeutic features of 64 patients consecutively treated at the Radiation Oncology Department Brescia University between January 1988 and April 2008. Materials: All the clinical, diagnostic and therapeutic features of the 64 cases were collected from the clinical records and analysed after their introduction in a general database. The different clinical and therapeutic features were analysed. Overall survival (OS) was calculated from the end of RT to the last follow-up. "Short" and "long" survivors were defined patients died within 1 and after 6 months from the end of RT, respectively. All statistical analysis were performed with SPSS 17th software. Results: In this series two peaks of accrual were observed: 1993 through 1997 and in the last two years (2006-2008). Most of the patients were immunocompetent (83%). Eleven patients had AIDS. Thirty-eight patients (59%) were aged > 60 years, 28 (44%) had IK <=70 and most of them had different neurological symptoms (95%). The symptoms were often differently combined but the most frequent were cognitive focal deficits in 43% (28 pts), depressed level of consciousness 20 % (13 pts); intracranial hypertension 15% (10 pts). The majority of these pts (61%) had histological confirmation of the diagnosis, the others only an unequivocal radiological diagnosis; 35 patients (54%) had high grade lymphoma. The first site of disease was mainly in the deep structures of the brain (64%). All the patients were treated with RT and 70% with RT alone. RT dose < 30 Gy was used mostly in young (< 60 years), HIV positives and KPS < 70 patients. "Palliative high dose approach" (≥ 30 Gy), older age, KPS ≥ 70, immunecompetency are significantly related with better OS at univariate analysis. Of these factors, RT dose does
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not retain significance at multivariate analysis, but it is associated with better OS when "short" and "long term" survivors are analyzed separately. Overall median survival was 187 days; actuarial OS at 1 and 5 years was 42% and 5% respectively. Conclusions: Age ≥ 60 years, normal immune status, good performance status are confirmed as important prognostic factors. High doses of RT and adherence to prescribed treatment are the most important predictive factors related to RT treatment. RT alone, also hypofractionated, with doses > 46 Gy can be considered in selected patients not eligible for radical treatment. 908 poster RISK OF CARDIAC AND VALVULAR DISEASE AFTER MANTLE OR INVOLVED NODE RADIOTHERAPY IN HODGKIN LYMPHOMA M. Maraldo1 , M. Aznar1 , P. Brodin1 , P. Munck af Rosenschöld1 , P. M. Petersen1 , I. R. Vogelius1 , L. Specht1 2 1 T HE F INSEN C ENTER - R IGSHOSPITALET, Copenhagen, Denmark 2 C OPENHAGEN U NIVERSITY, Faculty of Health Sciences, Copenhagen, Denmark Purpose: The risk of developing cardiac disease (CD) for long-term Hodgkin lymphoma (HL) survivors after mediastinal radiotherapy (RT) is under debate, as current data are, primarily, derived from patients treated with the outdated Mantle Field (MF) technique.In this work, we compare doses to the heart and four heart valves with Involved Node RT (INRT), the present standard of treatment, and MF. We also derive and compare the excess absolute risk (EAR) of developing CD using both techniques. Materials: We included 10 adolescents-young adults with clinical stage I-II HL. All patients were treated with chemotherapy and INRT (30-36 Gy). For each patient we simulated a MF, delivering 36 Gy.We derived a logistic doseresponse function for the 25 year risk of any CD and valvular disease (VD) using published data from a HL cohort[1]. For each patient we estimated the risk of any CD and VD from the individual dose volume histogram and the dose-response function. Results: For all 10 patients the mean heart dose was 4.9 Gy (range: 0.118 Gy) and 24.8 Gy (range: 18.6-28.8) with INRT and MF, respectively. For mean doses to the individual valves see fig. 1.The mean EAR 25 years after treatment was 0.8% (range: 0.4-3.5%) for CD and 0.04% (range: 0-2.46%) for any VD with INRT. For MF the mean EAR was 6.6% (range: 6-10. 1%) for CD and 8% (range: 2.7-14.4%) for any VD.
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909 poster TOTAL MARROW IRRADIATION AS SELECTIVE BOOST MODALITY AFTER CONVENTIONAL TBI FOR PATIENTS WITH ADVANCED HEMOPOIETIC MALIGNANCIES UNDERGOING AN ALLOGENEIC STEM CELL TRANSPLANT. S. Vagge1 , M. Zeverino2 , S. Agostinelli2 , S. Barra1 , F. Frassoni3 , G. Taccini2 , A. Bacigalupo3 , R. Corvò1 1 N ATIONAL I NSTITUTE FOR C ANCER R ESEARCH, Department of Radiation Oncology, Genova, Italy 2 N ATIONAL I NSTITUTE FOR C ANCER R ESEARCH, Medical Physics, Genova, Italy 3 A ZIENDA OSPEDALIERA UNIVERSITARIA S AN M ARTINO, Hematology, Genova, Italy Purpose: To report our clinical experience in planning and delivering Total Marrow Irradiation (TMI) after Total Body Irradiation (TBI) in patients with acute leukemia in relapse status or in second remission undergoing an allogeneic stem cell transplant (SCT). Materials: Patients received conventional TBI as 200 cGy BID/ day for 3 days boosted the next day by TMI (2 Gy in a single fraction) and followed by cyclophosphamide (Cy) 60 mg/ kg for 2 days. While TBI was delivered with linear accelerator, TMI was performed with helical tomotherapy (HT). Results: Seventeen patients were treated from July 2009 till August 2010, eleven with acute myeloid leukemia, five with acute lymphoid leukemia and one with myelodisplasia.. At the time of radiotherapy eight patients were in relapse, eight in second remission and one in third complete remission (CR) after relapse. The donor was a matched sibling in 7 cases, an unrelated donor in11 cases. Median organ-at-risk dose reduction with TMI ranged from 30% to 65% with the largest reduction (-50%-65%) achieved for brain, larynx, liver, lungs and kidneys. Target areas (bone marrow sites and spleen in selected cases) were irradiated with an optimal conformity and an excellent homogeneity. Follow-up ranges from 90 days to 530 days (median 320 days). However, tolerance was not different from a conventional TBI-Cy. All patients treated with TBI/TMI reached CR after SCT. Seven (41%) patients relapsed at median time of 276 days (range: 166- 446 days) . Eight (47%) patients have died, 5 for treatment-related toxicity and 3 for disease relapse. Nine (53%) patients are alive with five survivors in table clinical remission of disease Conclusions: This study confirms the clinical feasibility of using HT to deliver TMI as selective dose boost modality after TBI. Since the rate of relapse remains high after 14 Gy TBI/TMI, a dose escalation trial to determine the maximum tolerated dose of TMI given as multi-step boost irradiation is now starting at our institution for the treatment of patients with relapsed acute leukemia after previous SCT.
Normal tissue 910 poster ASSOCIATION BETWEEN SINGLE NUCLEOTIDE POLYMORPHISMS AND HAPLOTYPES IN THE VEGF GENE AND LATE TOXICITY IN PROSTATE CANCER PATIENTS T. Langsenlehner1 , E. M. Thurner1 , W. Renner1 , G. Hofmann1 , K. Kapp1 , U. Langsenlehner1 1 M EDICAL U NIVERSITY OF G RAZ, Graz, Austria
Fig. 1. The distribution of the mean dose to the whole heart and the four heart valves for our 10 patients for INRT (red) and MF (blue). The boxes represent 25-75% percentile and the whiskers represent the range. Conclusions: Our results show, that the mean dose to the heart and four heart valves was much lower with INRT compared with MF for most patients. However, for a subset of patients, even INRT plans will expose the heart and heart valves to high doses with a 25 year EAR of a cardiac event of up to 3.5%. For such patients the use of even more conformal techniques than INRT, and/or further dose reduction, is needed to minimize the risk of severe long-term complications. References[1] G. Schellong et al. Late valvular and other cardiac diseases after different doses of mediastinal radiotherapy for Hodgkin disease in children and adolescents. Pediatr Blood Cancer 2010;55:1145-1152.
Purpose: Vascular endothelial growth factor (VEGF) plays a key role in the regulation of angiogenesis and vascular permeability and has been shown to be up-regulated during the late phase of radiation injury. The present prospective study was performed to evaluate the association of VEGF single nucleotide polymorphisms (SNPs) and haplotypes with the development of radiation induced late side effects in prostate cancer patients. Materials: To analyze the role of VEGF polymorphisms and haplotypes for high-grade rectal or genitourinary late toxicity (defined as late toxicity RTOG ≥2) 493 prostate cancer patients from the Austrian PROCAGENE study treated with definitive radiotherapy were included in the present investigation. Seven candidate polymorphisms in the VEGF gene were selected and determined by 5-nuclease (TaqMan) assays. Haplotypes and linkage disequilibrium were determined using the Haploview program. Haplotype analysis showed two separate blocks of high-linkage disequilibrium, formed by five polymorphisms (-2578C>A, -2489C>T, -1498C>T, -634G>C, -7C>T) upstream of the coding sequence (promoter and 50-untranslated region) and two polymorphisms (936C>T and 1612G>A) downstream of the coding sequence. Results: Within a median follow-up time of 35 months, 42 patients (8.5%) developed high-grade late rectal toxicity and 47 patients (9.5%) late bladder toxicity. In a KaplanMeier analysis, carriers of the VEGF -7C>T polymorphism were at increased risk of high-grade late rectal toxicity (p= 0.003), in multivariate analysis including clinical and dosimetric parameters as potential confounders the VEGF -7C>T polymorphism remained a significant predictor for high-grade late toxicity (HR= 2.8, 95% CI 1.349 to 5.813; p= 0.006).