Late Toxicity In Patients Research Articles

Randomized Controlled Trial of Forward-Planned Intensity Modulated Radiotherapy for Early Breast Cancer: Interim Results at 2 Years

This single-center randomized trial was designed to investigate whether intensity-modulated radiotherapy (IMRT) reduces late toxicity in patients with early-stage breast cancer. The standard tangential plans of 1,145 nonselected patients were analyzed. The patients with inhomogeneous plans were randomized to a simple method of forward-planned IMRT or standard radiotherapy (RT). The primary endpoint was serial photographic assessment of breast shrinkage. At 2 years, no significant difference was found in the development of any photographically assessed breast shrinkage between the patients randomized to the interventional or control group (odds ratio, 1.51; 95% confidence interval, 0.83-1.58; p = .41). The patients in the control group were more likely to develop telangiectasia than those in the IMRT group (odds ratio, 1.68; 95% confidence interval 1.13-2.40; p = .009). Poor baseline surgical cosmesis resulted in poor overall cosmesis at 2 years after RT. In patients who had good surgical cosmesis, those randomized to IMRT were less likely to deteriorate to a moderate or poor overall cosmesis than those in the control group (odds ratio, 0.63; 95% confidence interval, 0.39-1.03, p = .061). IMRT can lead to a significant reduction in telangiectasia at comparatively early follow-up of only 2 years after RT completion. An important component of breast induration and shrinkage will actually result from the surgery and not from the RT. Surgical cosmesis is an important determinant of overall cosmesis and could partially mask the longer term benefits of IMRT at this early stage.

A Model-Based Estimate of Cumulative Excess Mortality in Survivors of Childhood Cancer

Although childhood cancer survival rates have dramatically increased, survivors face elevated risk for life-threatening late effects, including secondary cancer. To estimate the cumulative effect of disease- and treatment-related mortality risks on survivor life expectancy. State-transition model to simulate the lifetime clinical course of childhood cancer survivors. Childhood Cancer Survivor Study. Five-year survivors of childhood cancer. Probabilities of risk for death from the original cancer diagnosis, excess mortality from subsequent cancer and cardiac, pulmonary, external, and other complications, and background mortality (age-specific mortality rates for the general population) were estimated over the lifetime of survivors of childhood cancer. For a cohort of 5-year survivors aged 15 years who received a diagnosis of cancer at age 10 years, the average lifetime probability was 0.10 for late-recurrence mortality; 0.15 for treatment-related subsequent cancer and death from cardiac, pulmonary, and external causes; and 0.05 for death from other excess risks. Life expectancy for the cohort of persons aged 15 years was 50.6 years, a loss of 10.4 years (17.1%) compared with the general population. Reduction in life expectancy varied by diagnosis, ranging from 4.0 years (6.0%) for kidney tumor survivors to more than 17.8 years (> or =28.0%) for brain and bone tumor survivors, and was sensitive to late-recurrence mortality risk and duration of excess mortality risk. Estimates are based on data for survivors who received treatment 20 to 40 years ago; patients who received treatment more recently may have more favorable outcomes. Childhood cancer survivors face considerable mortality during adulthood, with excess risks reducing life expectancy by as much as 28%. Monitoring the health of current survivors and carefully evaluating therapies with known late toxicities in patients with newly diagnosed cancer are needed.

Late toxicity after postprostatectomy salvage radiation therapy

Purpose To evaluate late toxicity in patients who received salvage external beam radiotherapy (EBRT) for a detectable prostate-specific antigen (PSA) level after radical prostatectomy (RP). Methods A cohort of 308 consecutive patients underwent salvage EBRT from July 1987 through June 2003 for a detectable PSA level after RP. All were treated with high-energy photons (6–20 MV) to a median dose of 64.8 Gy (range: 54.0–72.4 Gy) in 1.8- to 2.0-Gy fractions. Results Median follow-up from the completion of EBRT was 60 months (range: 1 day–174 months). Late toxicity occurring more than 90 days after EBRT completion was identified in 41 patients (13%). Twelve patients (3.9%) had grade 2 urethral strictures and were treated with urethral dilation, 3 patients had grade 3 cystitis, and 1 had a grade 4 rectal complication. These numbers correspond to an estimated 0.7% (95% confidence interval, 0.0–1.6%) of patients experiencing a grade 3 or 4 complication by 5 years after the start of EBRT. Conclusions Salvage EBRT for a detectable PSA level after RP is the only curative treatment in this setting. This treatment can be administered in a manner that results in a low likelihood of late complications.

Toxicity of hypofractionated intensity-modulated radiotherapy in patients with prostate cancer

Objective To analyze the acute and late toxicities in patients with prostate cancer trea-ted with hypofractionated intensity-modulated radiotherapy (IMRT). Methods Between June 2006 and June 2008, 37 patients with prostate cancer were treated with hypofractionated IMRT. The clinical target vol-ume (CTV) was the prostate, seminal vesicles and pelvic lymph nodes in 24 patients, the prostate and semi-hal vesicles in 12, and only the tumor bed in 1. The dose per fraction was 2.3 - 2.8 Gy, with 2.7 Gy in 26 patients. The minimal dose was 62.5-75.0 Gy to the prostate and seminal vesicles, and 50 Gy to the pelvic lymph nodes. Results The median follow-up was 14 months. None of the patients experienced grade 4 a-cute gastro-intestinal (GI) toxicity. Grade 1, 2 and 3 acute GI toxicity occurred in 24.3%, 35.1% and 2.7% of the patients, respectively. The rectal V50>27% and V55>20% were highly significantly associat-ed with grade ≥1 acute GI toxicity. Grade 1,2 and 3 acute genitourinary (GU) toxicity occurred in 68%, 0% and 3% of the patients, respectively. The bladder V50> 10% was significantly associated with grade ≥1 acute GU toxicity. The incidence of late GI toxicity was low. No grade ≥3 late GI toxicity was observed. The incidence of late grade 1 and 2 GI toxicity was 24% and 5%, respectively. The rectal V65> 10% was highly significantly associated with grade ≥1 late GI toxicity. No late grade 4 GU toxicity was observed. The incidence of grade 1, 2 and 3 late GU toxicity was 49%, 11% and 3%, respectively. Grade ≥2 late GU toxicity was correlated with V40, V50 and mean dose of the bladder. Conclusions Acute and late toxicity of hypofractionated IMRT is acceptable in patients with prostate cancer. Key words: Prostate neoplasms/radiotherapy; Radiotherapy, hypofractionated; Radiotherapy, intensity-modulated; Side effects

Developing a CTCAEs patient questionnaire for late toxicity after head and neck radiotherapy

Purpose Patient-based reporting of symptoms is increasingly important in providing treatment toxicity information. However, observer-based scoring systems such as the CTCAEs which incorporate the LENT-SOMA scales are not adapted for patient-based reporting. We aim to (1) report the late toxicity in patients following head and neck radiotherapy using a LENT-SOMA patient-based questionnaire, (2) describe how the responses help to improve the questionnaire and (3) adapt the questionnaire for patient reporting using CTCAEs. Methods A 31-item LENT-SOMA patient questionnaire was administered prospectively to 220 patients pre-treatment and at eight time periods post-radical head and neck radiotherapy over 3 years. Exploratory factor analysis was carried out and questionnaire reliability was evaluated using Cronbach’s α coefficient. Results At 3-years follow-up, grade 3/4 toxicity was recorded for xerostomia (44%), hoarseness (14.3%), altered taste (6.1%) and oropharyngeal pain (1.9%). Factor analysis indicated that questionnaire division according to anatomical sub-site was reasonable. Cronbach’s α was 0.851 (95% CI: 0.820–0.883) indicating high reliability. Good compliance was obtained with all questions except for the ‘weight loss’ item. A satisfaction survey showed that the questionnaire was clear and concise. Teeth and mandible sections have been removed. Dietary change due to xerostomia has been incorporated in line with CTCAEs. LENT-SOMA scoring of analgesic needs and dysphagia not described in CTCAEs were found useful and have been retained. Conclusions The questionnaire has enabled reporting of late toxicity and the responses have enabled refinement of the questionnaire. It is reliable, feasible and has been validated for patient-based collection of CTCAEs late toxicity data.

Treatment parameters associated with acute and late toxicity in patients receiving accelerated partial breast irradiation using the MammoSite® brachytherapy device

Treatment parameters associated with acute and late toxicity in patients receiving accelerated partial breast irradiation using the MammoSite® brachytherapy device

Association of urethral toxicity with dose exposure in combined high-dose-rate brachytherapy and intensity-modulated radiation therapy in intermediate- and high-risk prostate cancer

Introduction To report acute and late toxicities in patients with intermediate- and high-risk prostate cancer treated with combined high-dose-rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT). Materials and methods From March 2003 to September 2005, 64 men were treated with a single implant HDR-B with 21 Gy given in three fractions, followed by 50 Gy IMRT along with organ tracking. Median age was 66.1 years, and risk of recurrence was intermediate in 47% of the patients or high in 53% of the patients. Androgen deprivation therapy was received by 69% of the patients. Toxicity was scored according to the CTCAE version 3.0. Median follow-up was 3.1 years. Results Acute grade 3 genitourinary (GU) toxicity was observed in 7.8% of the patients, and late grades 3 and 4 GU toxicity was observed in 10.9% and 1.6% of the patients. Acute grade 3 gastrointestinal (GI) toxicity was experienced by 1.6% of the patients, and late grade 3 GI toxicity was absent. The urethral V 120 (urethral volume receiving ⩾120% of the prescribed HDR-B dose) was associated with acute ( P = .047) and late ⩾ grade 2 GU toxicities ( P = .049). Conclusions Late grades 3 and 4 GU toxicity occurred in 10.9% and 1.6% of the patients after HDR-B followed by IMRT in association with the irradiated urethral volume. The impact of V 120 on GU toxicity should be validated in further studies.

Induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome (DeLOS-I-trial)

A prospective multicenter phase-II trial (12 centers) was performed by the German larynx organ preservation group (DeLOS) to evaluate the effect of induction chemotherapy (ICHT) with paclitaxel/cisplatin (TP), followed by accelerated-hyperfractionated (concomitant boost) radiotherapy (RT) in responders. The trial was focused on larynx preservation, tumor control, survival, salvage surgery and late toxicity in patients with advanced larynx/hypopharynx carcinoma eligible for total laryngectomy (LE). Seventy-one patients (40 larynx, 87.5% St. III, IV; 31 hypopharynx, 93.4% St. III, IV) were enrolled into the study and treated with ICHT (200 mg/m(2) paclitaxel, 100 mg/m(2) cisplatin; day 1, 22) according to the DeLOS protocol. Patients with complete or partial tumor response proceeded to RT (69.9 Gy in 5.5 weeks). Non-responders received a LE followed by postoperative RT (56-70 Gy in 5.5-7 weeks). The response rate to ICHT for larynx cancer was 69.6% (7.1% complete, 62.5% partial response) and for hypopharyngeal cancer was 84.3% (6.9% complete, 77.4% partial response). Overall survival after 36 months was 60.3% (95% CI, 48.4-72.2%), after 42 months was 56.5% (95% CI, 44.2-68.8%). Laryngectomy-free survival was as follows: after 36 months, 43.0% (95% CI, 30.9-55.0%); after 42 months, 41.3% (95% CI, 29.3-53.3%). Both parameters did not show different outcomes after distinguishing larynx from hypopharynx. LE was indicated in 15 non-responders after ICHT. Five of the 15 non-responders refused the laryngectomy. Two of the five received RT instead and had no evidence of disease 42 months after RT. Late toxicity (dysphagia III, IV LENT SOMA score in laryngectomy-free survivors: after 6 months, 1.8%; 12 months, 11.4%; 18 months, 14.5%; 24 months, 8.1%; 36 months, 16%) and salvage surgery (4 pharyngocutaneous fistulas in 27 operations) were tolerable. In a large portion of patients eligible for LE, the larynx could be preserved with satisfying functional outcome. Good responders after ICHT had also a good general outcome with relatively rare severe late toxicities. Due to a slight increase of relevant late dysphagia, functional outcome regarding swallowing and tracheotomy free breathing should be more focused in future larynx organ preservation trials.

Risk of Late Toxicity After Radiotherapy in Patients With Connective Tissue Disorders: Association With Connective Tissue Disorder Severity

There is no way to reliably identify which patients with connective tissue disorders (CTDs) are at greatest risk of radiotherapy-related complications. Building on our prior experience, we have postulated that CTD severity, as measured by the number of organ systems involved, may be predictive of chronic radiation toxicity risk. Medical records of 43 patients with CTDs (20 patients with scleroderma and 23 patients with systemic lupus erythematosus) who received radiotherapy at Mayo Clinic were reviewed. Risk of radiotherapy-related late toxicity was analyzed for patients as a function of CTD severity. The division of patients into high- and low-severity CTD groups was made at the 50th percentile of the number of organ systems involved with the CTD (low-severity CTD included patients with 2 to 3 organ systems involved for scleroderma and 2 to 4 organ systems for lupus; high-severity CTD included patients with 4 to 5 organ systems involved for scleroderma and 5 to 6 organ systems involved for lupus). All 20 scleroderma patients, and 17 of 23 lupus patients, were evaluable for long-term complications. For patients with low-severity CTD, the 5- and 10-year chronic toxicity rates of any grade were 41% (95% CI, 19%–67%) and 52% (95% CI, 26%–88%), respectively. For patients with high-severity CTD, 5- and 10-year chronic toxicity rates of any grade were 79% (95% CI, 52%–93%) and 79% (95% CI, 52%–93%), respectively. Univariate analysis revealed a significant difference in the risk of late toxicity of any grade for patients with high-severity CTD when compared to patients with low-severity CTD (Figure; p = 0.006). No significant difference between the two groups could be demonstrated when analyzing risk of grade 3 or higher late toxicity (p = 0.56), possibly because relatively few patients experienced grade ≥3 late toxicity events (3 patients among the 20 with scleroderma, 4 patients among the 17 with lupus). This study suggests that the severity of the CTD, as estimated by the number of organ systems involved, is one piece of information the clinician may use in evaluating the risk of radiotherapy-related late toxicity in patients with scleroderma or lupus.

Can Serum Markers Be Used to Predict Acute and Late Toxicity in Patients With Lung Cancer?

To identify factors that are predictive of satisfactory acute and long-term pulmonary tolerance of definitive irradiation and, conversely, factors that are predictive of excessive impairment of pulmonary functions. To determine if there is any correlation between early elevation of biochemical markers obtained in blood of irradiated patients and subsequent pulmonary abnormalities as detected by clinical findings, pulmonary function tests, and/or radiographic findings of pneumonitis/fibrosis. This was a multi-institutional prospective trial sponsored by the Radiation Therapy Oncology Group. Eligible patients had surgically unresectable or medically inoperable stage II or III non-small cell lung cancer. Pretreatment evaluation included baseline dyspnea index (BDI) and pulmonary function tests (PFT). Radiation therapy consisted of once-daily treatment with 2 Gy to a total of 60 to 66 Gy. A quantitative nuclear medicine perfusion study was correlated to the radiation therapy portals to assess the proportion of lung irradiated. Blood for serum markers (surfactant apoprotein, procollagen type III, interleukin [IL]-1, interleukin-6, and tumor necrosis factor-alpha) was drawn prior to the beginning of radiation therapy and then weekly during treatment (at 10, 20, 30, 40, 50, and 60 Gy). Post-treatment follow-up included PFT every 3 months for 1 year and then annually. The BDI was reevaluated at the same intervals. There were 127 analyzable patients. Squamous cell carcinoma was the predominant histology and 93% of the patients had AJCC stage III disease. The median survival time is 10.9 months with 43% of patients living 1 year and 10% living 3 years. Grade >or=2 acute lung toxicity was seen in 18% of patients; patients least likely to develop lung toxicity are those with undetectable levels of IL-6 at 10 Gy and diffusing capacity of the lung for carbon monoxide percent (DLCO%) >54. Patients most likely to develop acute toxicity are those with elevated IL-6 and age >60 years. Grade >or=2 late lung toxicity was seen in 30% of patients. Karnofsky performance status was the only pretreatment factor predictive of late lung toxicity. The proportion of lung within the irradiated field, BDI indices, physician-assessed baseline dyspnea, and baseline PFT were not predictive of pulmonary toxicity. Using grade >or=2 toxicity as an event, age >60 years, gender, and a surfactant level <797 at 20 Gy were predictive of late lung toxicity. Elevated levels of serum IL-6 after 10 Gy of lung irradiation appear to predict grade >or=2 acute lung toxicity, and high serum levels of surfactant apoproteins at 20 Gy correlated with grade >or=2 late pulmonary toxicity. These findings need to be confirmed but could be useful in a model to predict risk of pulmonary injury with high doses of radiation. For future studies, it is necessary to evaluate serum markers at multiple time-points during treatment, and quality control is critical during the collection, storage, and analysis of these serum markers.

2442: Concomitant Radiochemotherapy for Locally Advanced Oropharynx Carcinoma : Late Toxicity Results - A Retrospective Single Institution Study

To retrospectively assess 5-year late toxicity in patients treated in a single institution by concomitant radiochemotherapy for locally advanced oropharynx carcinoma using two different toxicity scales.

Radiothérapie prophylactique des aires ganglionnaires dans le cancer du sein

In breast cancer patients, the incidence of involvement of the regional lymph nodes and the risk for developing a locoregional recurrence are highly influenced by several prognostic factors. A meta-analysis of the EBCTCG showed a reduction of about 70% of the locoregional recurrence rate with radiotherapy for all patients, independent of age, characteristics of the tumour or the administration of systemic treatment. At the same time, this meta-analysis confirmed that radiotherapy can lead to an increased risk for developing contralateral breast cancer and to an increase in the risk of non-breast cancer related mortality, mainly due to cardiac and pulmonary toxicity. Because of this, the net effect of regional radiotherapy will be strongly influenced by the individual risk factors of the patients and by the quality of the technical aspects of the radiotherapy. The thin line between the benefits of elective regional lymph node irradiation and the possible late toxicity for patients with early stage breast cancer is currently the subject of several prospective randomised trials, the results of which will only become available in several years. Moreover, recent developments in the field of novel prognostic factors will open completely new ways to be explored, which might give us new tools for estimating the individual benefit/risk ratio for every single patient.

Phase II trial of radiotherapy after hyperbaric oxygenation with chemotherapy for high-grade gliomas

We conducted a phase II trial to evaluate the efficacy and toxicity of radiotherapy immediately after hyperbaric oxygenation (HBO) with chemotherapy in adults with high-grade gliomas. Patients with histologically confirmed high-grade gliomas were administered radiotherapy in daily 2 Gy fractions for 5 consecutive days per week up to a total dose of 60 Gy. Each fraction was administered immediately after HBO with the period of time from completion of decompression to irradiation being less than 15 min. Chemotherapy consisted of procarbazine, nimustine (ACNU) and vincristine and was administered during and after radiotherapy. A total of 41 patients (31 patients with glioblastoma and 10 patients with grade 3 gliomas) were enrolled. All 41 patients were able to complete a total radiotherapy dose of 60 Gy immediately after HBO with one course of concurrent chemotherapy. Of 30 assessable patients, 17 (57%) had an objective response including four CR and 13 PR. The median time to progression and the median survival time in glioblastoma patients were 12.3 months and 17.3 months, respectively. On univariate analysis, histologic grade (P=0.0001) and Karnofsky performance status (P=0.036) had a significant impact on survival, and on multivariate analysis, histologic grade alone was a significant prognostic factor for survival (P=0.001). Although grade 4 leukopenia and grade 4 thrombocytopenia occurred in 10 and 7% of all patients, respectively, these were transient with no patients developing neutropenic fever or intracranial haemorrhage. No serious nonhaematological or late toxicities were seen. These results indicated that radiotherapy delivered immediately after HBO with chemotherapy was safe with virtually no late toxicity in patients with high-grade gliomas. Further studies are required to strictly evaluate the effectiveness of radiotherapy after HBO for these tumours.

Association of DNA Repair and Steroid Metabolism Gene Polymorphisms with Clinical Late Toxicity in Patients Treated with Conformal Radiotherapy for Prostate Cancer

To explore the possible relationship between single nucleotide polymorphisms (SNP) in candidate genes encoding DNA damage recognition/repair/response and steroid metabolism proteins with respect to clinical radiation toxicity in a retrospective cohort of patients previously treated with three-dimensional conformal radiotherapy (3-DCRT) for prostate cancer. One hundred twenty-four patients with prostate cancer underwent 3-DCRT at our institution between September 1996 and December 2000. Of these, 83 consented for follow-up of blood sampling and SNP analysis. Twenty-eight patients were documented as having experienced grade >/=2 late bladder or rectal toxicity (scoring system of Radiation Therapy Oncology Group) on at least one follow-up visit. We analyzed 49 SNPs in BRCA1, BRCA2, ESR1, XRCC1, XRCC2, XRCC3, NBN, RAD51, RAD52, LIG4, ATM, BCL2, TGFB1, MSH6, ERCC2, XPF, NR3C1, CYP1A1, CYP2C9, CYP2C19, CYP3A5, CYP2D6, CYP11B2, and CYP17A1 genes using the Pyrosequencing technique. Significant univariate associations with late rectal or bladder toxicity (grade >/=2) were found for XRCC3 (A>G 5' untranslated region NT 4541), LIG4 (T>C Asp(568)Asp), MLH1 (C>T, Val(219)Ile), CYP2D6*4 (G>A splicing defect), mean rectal and bladder dose, dose to 30% of rectum or bladder, and age <60 years. On Cox multivariate analysis, significant associations with toxicity were found for LIG4 (T>C, Asp(568)Asp), ERCC2 (G>A, Asp(711)Asp), CYP2D6*4 (G>A, splicing defect), mean bladder dose >60 Gy, and dose to 30% of rectal volume >75 Gy. In this study, we identified SNPs in LIG4, ERCC2, and CYP2D6 genes as putative markers to predict individuals at risk for complications arising from radiation therapy in prostate cancer.

CEBOPP/VIML Followed by Radiotherapy for Intermediate- and Advanced-Stage Hodgkin's Disease: A Long-Term Analysis.

Introduction. To improve treatment results and minimize acute and late toxicity in patients (pts) with intermediate- or advanced-stage Hodgkins disease, a combined modality treatment consisting of a response-adapted chemotherapy (CTX) and radiotherapy (RTX) was used. G-CSF was added in pts who developed severe or prolonged neutropenia or infection during CTX. Patients and treatment. From 10/90 to 2/04, 189 consecutive pts (53% males, 47% females) with a median age of 33 yrs (range 16–78) without prior treatment were included. Inclusion criteria were intermediate stage (I–II with risk factor or IIIA without risk factor) or advanced stage (IIB or IIIA with risk factor or IIIB or IV). Pt characteristics: 2% stage I, 54% stage II, 26% stage III, 18% stage IV disease. 48% B-symptoms, 87% bulky tumors (=/>5cm), 20% extranodal involvement, 14% spleen involvement, 65% high ESR, 31% abnormal LDH (>240 U/L). CTX started with cyclophosphamide (400 mg/m2 d3,4), epirubicin (40 mg/m2 d1,2), bleomycin (30 mg d1,10, 3 cycles in all pts and 2 cycles in pts who were going to receive mediastinal irradiation), vincristine (2 mg d1,10), prednisone (100 mg/m2 d1-10), and procarbazine (60 mg/m2 d1-10) (CEBOPP) repeated every 3 wks. In pts with no residual tumor after 4 cycles, CEBOPP was continued for further 2 cycles. In pts with progressive disease during treatment with CEBOPP or partial remission (PR) after 4 cycles, therapy was switched to VP-16 (130 mg/m2 d1,3,5), ifosfamide (1300 mg/m2+mesna d1-5), methotrexate (70 mg/m2+leucovorin rescue d1,5) (VIML) repeated every 3 wks for 2–4 cycles. CTX was followed by RTX (30 Gy, 40 Gy in case of bulky disease or residual tumor) predominantly given to IF in stage I-II and stage III disease with <3 involved regions.Results. Median duration of CTX was 4 months. The most frequent treatment toxicities were alopecia, leukocytopenia, and peripheral neuropathy. 42% of pts needed G-CSF during CTX. Toxic deaths occurred in 2 pts (1%). 82% of pts received additional RTX. An overall response rate of 99%, including 70% complete remissions (no residual tumor or residual tumor</=2cm) and 29% partial remissions (residual tumor>2cm) was achieved. With a median follow-up of 6 yrs, the probability of event-free survival (EFS) and overall survival (OS) for the entire group of pts is 82% and 87% at 10 yrs, respectively. The probability of EFS and OS for pts with intermediate stage (n=83) is 86% and 88% and for pts with advanced stage (n=106) 79% and 86%, respectively. Myelodysplasia occurred in 1 pt (0.5%) and secondary neoplasia possibly related to treatment as solid tumor in 6 (3%) and as non-Hodgkin lymphoma in 2 (1%) pts.Conclusion. Based on these results, CEBOPP/VIML followed by RTX appears to be highly effective in achieving long-term EFS and OS in pts with intermediate- or advanced-stage Hodgkins disease. These data compare favourably with the results of recent studies reported for these groups of pts.

P-208 Late toxicity in patients with locally advanced non-small cell lungcancer treated with combined radiochemotherapy

P-208 Late toxicity in patients with locally advanced non-small cell lungcancer treated with combined radiochemotherapy

Feasibility of RNA collection for micro-array gene expression analysis in the treatment of cervical carcinoma: a scientific correlate of RTOG C-0128

Purpose To determine the feasibility of RNA collection in a multi-institutional cooperative group setting to be utilized for micro-array gene expression analysis, and to describe the methodology. Methods RTOG C0128, a phase I–II, protocol was designed to look at the safety and efficacy of external beam radiation therapy to 45 Gy with concomitant 5-FU and cisplatin chemotherapy, brachytherapy to deliver 85 Gy to point A, and Celecoxib at 400 mg twice daily for 1 year. Patients had the option of participating in a tissue collection portion of the protocol to be utilized for micro-array gene expression analysis before treatment and at the time of the first implant. RNA quality was determined by two parameters: the absorbance ratio at 260 nm/280 nm, and by the ratio of the integrated peak of 28S RNA to 18S RNA after gel electrophoresis. Results From August 2001 to March 2004, 84 patients were accrued to the trial, and tissue was obtained prior to initiation of therapy on 34 patients (40%). FIGO stages for the patients who provided tissue were IB (23%), II (57%), and IIIA–IVA (20%). Additionally, biopsies were obtained at the time of the first implant from 22 of the accrued patients making paired samples available on 26% for RNA extraction and micro-array gene expression analysis. The mean ± SEM amount of tissue obtained pretreatment was 97 ± 13 mg compared with 51 ± 8 mg for tissue obtained at the time of the first implant ( P = 0.009). The mean total RNA extracted from the samples prior to treatment was 119 ± 19 μg versus 35 ± 6 μg at the time of the first procedure ( P = 0.001). The RNA quality was assessed via the absorbance ratio at 260 nm divided by 280 nm. The mean values pretreatment and at first implant were 1.87 ± 0.07 versus 1.66 ± 0.11, respectively ( P = 0.002); however, the integrated peak of 28S RNA to 18S RNA after gel electrophoresis was not significantly different ( P = 0.26). Conclusions RNA extraction for gene expression analysis can be successfully performed in the multi-institutional cooperative group setting. Fresh tissue samples were obtained on 40% of accrued patients prior to treatment. The amount of biopsy material and the quantity of RNA extracted were greater prior to treatment compared with the first implant. The quality of RNA was superior prior to treatment as measured by the ratio of absorbance at 260/280 nm. These results indicate that gene expression analysis is feasible in the cooperative group setting utilizing amplification techniques for the RNA. Hopefully, this will allow for improvement in prognosis, therapeutic development, and correlation with acute and late toxicities in patients with cancer.

152 Late toxicity in patients treated with concurrent chemotherapy and radiotherapy for head and neck cancers

152 Late toxicity in patients treated with concurrent chemotherapy and radiotherapy for head and neck cancers

51 oral Single nucleotide polymorphisms in radiation response genes correlate with clinical late toxicity in patients treated with three-dimensional conformal radiotherapy (3DCRT) for adenocarcinoma of the prostate

51 oral Single nucleotide polymorphisms in radiation response genes correlate with clinical late toxicity in patients treated with three-dimensional conformal radiotherapy (3DCRT) for adenocarcinoma of the prostate

80 Association of radiation and tissue homeostasis response gene polymorphisms with clinical late toxicity in patients treated with three-dimensional conformal radiotherapy (3DCRT) for adenocarcinoma of the prostate

80 Association of radiation and tissue homeostasis response gene polymorphisms with clinical late toxicity in patients treated with three-dimensional conformal radiotherapy (3DCRT) for adenocarcinoma of the prostate