Acute Toxicity In Patients Research Articles

Acute Toxicity in Patients With HER2-Positive Breast Cancer Treated With Adjuvant Radiation Therapy and Concurrent Trastuzumab and Pertuzumab

Acute Toxicity in Patients With HER2-Positive Breast Cancer Treated With Adjuvant Radiation Therapy and Concurrent Trastuzumab and Pertuzumab

Comparison of dosimetric parameters and acute toxicity of intensity-modulated and three-dimensional radiotherapy in patients with cervix carcinoma: A randomized prospective study

PurposeThe use of intensity-modulated radiotherapy (IMRT) to treat cervix carcinoma has increased, however prospective randomized trials are still lacking. AimTo compare the dosimetric parameters and associated acute toxicity in patients with cervix carcinoma treated with three-dimensional (3D) conformal radiotherapy and IMRT. Patients and methodsForty patients were randomized in two arms each consisting of 20 patients. Patients in both arms received concurrent chemoradiation (cisplatin 40mg/m2 weekly; 50Gy/25 fractions). Patients were treated with 3D conformal radiotherapy in one arm and with IMRT in another arm. After external beam radiotherapy, all patients received brachytherapy (21Gy/3 fractions at weekly interval). For dosimetric comparison, both kinds of the plans were done for all the patients. All patients were assessed throughout and until 90 days after completion of treatment for acute gastrointestinal, genitourinary and hematologic toxicities. ResultsBoth plans achieved adequate planning target volume coverage, while mean conformity index was found significantly better in IMRT plans (P-value=0.001). D35 (dose to 35% volume) and D50 for bladder was reduced by 14.62 and 32.57% and for rectum by 23.82 and 43.68% in IMRT. For IMRT, V45 (volume receiving 45Gy) of bowel were found significantly lesser (P-value=0.0001), non-tumour integral dose was found significantly higher (P-value=0.0240) and V20 of bone marrow was found significantly reduced (P-value=0.019) in comparison to that in 3D conformal radiotherapy. Significant reduction of grade 2 or more (20 vs 45%; P-value=0.058) and grade≥3 (5 vs 15%, P-value=0.004) acute genitourinary toxicity and grade 2 or more (20 vs 45%, P-value=0.003) and grade 3 or more (5 vs. 20%, P-value=0.004) acute gastrointestinal toxicity while no significant difference for grade 2 and 3 or more haematological toxicity was noted in patients treated with IMRT compared to 3D conformal radiotherapy. ConclusionIMRT provide a good alternative for treatment of cervix carcinoma with lower acute gastrointestinal and acute genitourinary toxicity with similar target coverage compared to 3D conformal radiotherapy.

Factors associated with acute toxicity during chemoradiation therapy for rectal cancer.

734 Background: Acute toxicity may be a factor interfering with receipt of chemoradiation (CRT) therapy for rectal cancer. The purpose of this study was to identify clinical and treatment factors associated with increased acute toxicity in patients receiving CRT therapy for rectal cancer. Methods: We identified patients with rectal adenocarcinoma treated with CRT between 2006-2014 at an NCI-designated cancer center. Patients with metastatic disease or missing treatment information were excluded. Acute toxicity information including weight loss, pain, fatigue, constipation, diarrhea, anorexia, and performance status was extracted from weekly on treatment visit notes. Multivariable logistic regression was used to assess predictors of grade 3+ toxicity using covariates significant on univariable analysis. Results: A total of 148 patients were included with a median age of 59 (range 29-99). The majority of patients were male (55%) and received 5-FU based chemotherapy (82%). During CRT, 35 (24%) patients experienced at least one grade 3+ toxicity: 13 (9%) patients experienced grade 3+ fatigue, 1 (1%) experienced grade 3+ constipation, 11 (7%) experienced grade 3+ diarrhea, 14 (10%) experienced grade 3+ pain, and 11 (7%) experienced grade 3+ anorexia. Eight (5.4%) patients had an ECOG performance status > 3 and 28 (19%) patients had weight loss > 5 lbs during CRT. On multivariable analysis, increased distance from the anal verge (OR 0.78 95% CI 0.636-0.998) was associated with a decreased risk for grade 3+ pain and age > 75 was associated with an increased risk of grade 3+ anorexia (OR 6.07 95% CI 1.067-34.56). Clinical T4 disease was associated with an increased risk of weight loss > 5 lbs (OR 0.17 95% CI 0.100-0.446). On multivariable analysis, there were no factors associated with grade 3+ fatigue, diarrhea, or constipation. There were no factors associated with a decline in performance status to > 3 while on treatment. Conclusions: Our results suggest that rectal cancer patients who are older, have more advanced disease, or with low lying tumors may be at an increased risk for treatment-related toxicity. Identifying predictors of toxicity may allow for tailored interventions to minimize toxicity for these patients.

Comparison between helical tomotherapy and intensity-modulated radiotherapy on acute toxicity in patients with rectal cancer

Objective To compare acute toxicity for stage Ⅱ-Ⅲ patients with rectal cancer irradiated with helical tomotherapy (HT) and conventional five-field intensity-modulated radiotherapy (5-IMRT). Methods The data of 84 stage Ⅱ-Ⅲ patients with rectal adenocarcinoma treated with concurrent chemoradiotherapy (CRT) were retrospectively analyzed. 19 patients underwent postoperative CRT, and 65 patients underwent preoperative CRT. 43 patients received radiotherapy with HT and 41 patients with 5-IMRT. The delineation on clinical target volume (CTV) and gross tumor target (GTV) was similar for two groups. The CTV to plan tumor volume (PTV) margins were 1.0 cm for patients with 5-IMRT and 0.5 cm for patients with HT. For all patients, a dose of 45.0-50.4 Gy, in daily fractions of 1.8 Gy, was delivered to PTV. For 45 patients with high risk factors, simultaneous integrated boost (SIB) was given to the tumor or tumor bed of a total dose of 55.0-60.0 Gy, in daily fractions of 2.1-2.3 Gy. Before treatment, the patients treated with HT underwent scanning by the tomotherapy-integrated megavoltage computed tomography (MVCT) scan modality and were positioned by co-registration of these images to the original kilovoltage planning CT image set. Concurrent capecitabine every day 1 600 mg/m2, twice daily on every day in the week. Results The rates of grade ≥2 acute cystitis were 7.0 % (3 cases) in HT group and 2.4 % (1 case) in 5-IMRT group (P= 0.616), and ≥3 grade acute diarrhea were 4.7 % (2 cases) and 12.2 % (5 cases), respectively (P= 0.259). ≥2 grade leukopenia were 48.8 % (21 cases) and 19.5 % (8 cases), respectively (P= 0.005), ≥1 grade anemia were 34.9 % (15 cases) and 14.6 % (6 cases), respectively (P= 0.032), and ≥1 grade thrombocytopenia were 23.3 % (10 cases) and 14.6 % (6 cases), respectively (P= 0.314). Conclusions There is no significant difference in acute diarrhea and cystitis for patients treated with HT and 5-IMRT. Leukopenia and anemia in patients treated with HT are worse than those in patients with 5-IMRT, and thrombocytopenia is similar in the two groups. Key words: Rectal neoplasms; Chemoradiotherapy; Helical tomotherapy; Acute toxicity

Abstract P2-12-07: The association between exercise behavior and patient-reported outcomes in women with early breast cancer receiving locoregional radiation therapy

Abstract Purpose/Objectives: RT is associated with acute treatment-related complications that can lead to poor quality of life (QOL) and fatigue. Exercise has been shown in other cancer treatment settings to improve negative outcomes. We conducted a prospective pilot study to explore the association between exercise, patient-reported outcomes (PROs), and radiation therapy (RT) toxicities. Materials/Methods: Patients with surgically excised ductal carcinoma in situ or invasive breast carcinoma receiving curative radiation were enrolled. Each patient completed an exercise behavior/QOL survey at two time points: before the patient’s 5th fraction of radiation and during the last week of treatment. Limb girth measurements to evaluate lymphedema and assessment of shoulder range of motion (ROM) were completed on all patients at the same two time points. Skin toxicity was assessed weekly throughout radiotherapy. Exercise behavior was quantified with the Godin Leisure Time Exercise Questionnaire (metabolic equivalent [MET] hours per week). Patients with >7 METs/week were designated the exercise cohort (n=10) and those with <7METs/week the non-exercise cohort (n=10). PROs were measured using standardized questionnaires. Continuous variables were compared using the Wilcoxon rank sum test and percentages were compared using Fisher’s exact test. Results: Median patient age was 56 (range 28-70) years. Median MET in the exercise cohort was 12.9/week (range 7.5-35.0, n=10); 0.0/week in the non-exercise cohort (range 0-5.8, n=10). Women in the exercise cohort experienced significant improvement in depression scores over the course of treatment as compared to those who did not exercise (p=0.013). Those in the exercise cohort also reported less fatigue on the FACT-Fatigue subscale at treatment completion (exercise: 133.0; non-exercise: 121.0) (p=0.6). In addition, only 30% of exercisers suffered from grade 2 dermatitis compared to 70% of non-exercisers (p=0.2), despite a similar body mass index (26.4 exercise cohort versus 28.1 non-exercise). Exercisers also had greater ROM in the affected (91.7 vs. 85.2%, p=0.1) and contralateral shoulder (95 vs. 90%, p=0.048) at treatment completion. No differences in pain or sleep scores were noted and lymphedema was mild (<3cm) in the entire patient cohort. Conclusion: The vast majority of current exercise oncology literature indicates that physical activity is an independent predictor of quality of life metrics in cancer patients. Our study notes a trend towards improved outcomes with increased exercise during radiation therapy, suggesting that accrual of additional patients to our pilot study is worthwhile. Ultimately, a concurrent exercise intervention may improve quality of life and reduce acute toxicity in patients undergoing breast radiation treatment. Citation Format: Ritu Arya, Lee W Jones, Rachel C Blitzblau, Manisha Palta, Lisa Massa, Gloria Broadwater, Janet K Horton. The association between exercise behavior and patient-reported outcomes in women with early breast cancer receiving locoregional radiation therapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-12-07.

Acute Toxicities Associated With 3-Dimensional Conformal External-Beam Accelerated Partial Breast Irradiation in a Prospective Phase 2 Trial

This study aimed to evaluate acute toxicities in patients enrolled in a prospective phase 2 trial on accelerated partial breast irradiation (APBI) using three-dimensional conformal radiation therapy (3D-CRT) at a dose of 30 Gy in 5 fractions every other day.

P0164 Toxicity profiles of adjuvant docetaxel-cyclophosphamide in Asian compared with caucasian patients with breast cancer

Background Ethnic differences in treatment-related toxicities exist between Eastern and Western patients. Our previous retrospective study has demonstrated racial differences in acute toxicities in patients receiving anthracycline-based chemotherapy. In this retrospective study, we aimed to compare the difference in tolerance to adjuvant docetaxel-cyclophosphamide (TC) between patients of different ethnicities. Methods Data were collected from six international breast cancer centres at which patients were planned for treatment with adjuvant TC (docetaxel 60–75 mg/m 2 and cyclophosphamide 600 mg/m 2 every 21 day for four cycles). Haematological toxicities were assessed by first episode of grade 2 or higher toxicity and disease-free survival was also evaluated. Findings From March 2004 to July 2013, 127 Asian patients (80 Chinese, 46 Japanese, and one Filipino) and 100 Caucasian patients were retrospectively compared for treatment-related toxicities. Baseline demographics and tumour characteristics were different between Asians and Caucasians. When compared to Caucasians, more Asians were premenopausal (61/126, 48.4% versus 30/95, 31.6%; p = 0.013) and less obese (6/127, 4.7% versus 21/100, 21.0%; p p p = 0.027). During the four cycles of chemotherapy, Asians had a significant higher rate of grade ⩾ 2 neutropenia than Caucasians (58/127, 45.7% versus 6/100, 6.0%; p p = 0.046) (table). Differences in grade ⩾ 3 neutropenia were also noted (39/127, 30.7% versus 4/100, 4.0%, p p = 0.764). Other hematological and non-hematological toxicities were much the same between the two ethnic groups. Of 205 patients eligible for survival analysis, 188 (91.7%) patients were disease-free and no significant difference in disease-free survival was observed between Asians and Caucasians at a median follow-up of 23 months. Interpretation Ethnic differences in toxicity profile were noted between Asian and Caucasian patients receiving TC, suggesting the possibility of different pharmcogenomics between ethnic groups. Further validation is essential to underpin differential treatment paradigms for various ethnic groups.

Clinical Comparison of IMRT With 3D-CRT in Preoperative Chemoradiation Therapy for Locally-Advanced Rectal Cancer (LARC)

Preoperative chemoradiation (CRT) is the standard neoadjuvant treatment in patients with LARC. We designed this study to compare the potential advantages of IMRT and 3DCRT in locoregional control and acute toxicity in patients with LARC.

A comparative study of intensity-modulated radiotherapy with concurrent PF or TP chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma

Objective To investigate the survival data and acute toxicities in patients with locoregionally advanced nasopharyngeal carcinoma who receive intensity-modulated radiotherapy (IMRT)with concurrent chemotherapy using nedaplatin plus 5-fluorouracil (PF) or taxol plus nedaplatin (TP).Methods A retrospective analysis was performed on the clinical data of 152 patients with stage Ⅲ or Ⅳa nasopharyngeal carcinoma who were admitted to our hospital in 2009-2010.Of the 152 patients,80 received IMRT with concurrent PF chemotherapy,and 72 received IMRT with concurrent TP chemotherapy;there were at least 2 cycles of concurrent chemotherapy in both groups.The Kaplan-Meier method was used to calculate the survival rates,and the log-rank test was used to analyze the survival difference ; the chisquare test was used to compare the acute toxicities in the two groups.Results The follow-up rate was 100％.The 2-year relapse-free survival rate,distant metastasis-free survival rate,progression-free survival rate,and disease-specific death rate for the IMRT/PF group were 95％,82％,81％,and 13％,respectively,versus 97％,83％,79％,and 12％ for the IMRT/TP group (x2 =0.03,0.02,0.62,and 0.22,P=0.861,0.881,0.431,and 0.638).The incidence rates of leukopenia (grade ≥3),neutropenia (grade ≥ 3),thrombocytopenia (grade ≥ 3),ALT elevation (grade ≥ 2),and oral mucositis (grade ≥3) for the IMRT/PF group were 33％,23％,14％,8％,and 12％,respectively,versus 60％,47％,28％,18％,and 25％ for the IMRT/TP group (x2 =11.33,10.29,4.59,3.94,and 3.94,P =0.001,0.001,0.032,0.047,and 0.047).Conclusions Compared with IMRT with concurrent PF chemotherapy,IMRT with concurrent TP chemotherapy does not lead to significantly better survival and results in more acute toxicities in the patients with locoregionally advanced nasopharyngeal carcinoma. Key words: Nasopharyngeal neoplasms/intensity-modulated radiotherapy; Nasopharyngeal neoplasms/concurrent chemotherapy; Prognosis

11C Choline PET Guided Salvage Radiotherapy with Volumetric Modulation Arc Therapy and Hypofractionation for Recurrent Prostate Cancer after HIFU Failure: Preliminary Results of Tolerability and Acute Toxicity

The purpose of this work was to evaluate tolerance, feasibility and acute toxicity in patients undergoing salvage radiotherapy after high-intensity focused ultrasound (HIFU) failure. From 2005 to 2011 a total of 15 patients were treated with HIFU as primary radical treatment. Between July 2011 and February 2013, all 15 patients presented biochemical relapse after HIFU and 11C choline PET documenting intrapostatic-only failure. Salvage EBRT was performed with moderate hypofractionation schedule in 28 fractions with volumetric modulation arc therapy (VMAT). Genito-urinary (GU) and rectal and bowel toxicity were scored by common terminology criteria for adverse events version 4 (CTCAE V.4) scale. Biochemical response was assessed by ASTRO Phoenix criteria. Median age of patients was 67 years (range: 53-85). The median Gleason score was 7 (range: 6-9). The median prostate specific antigen (PSA) at the time of biochemical relapse after HIFU was 5.2 ng/mL (range: 2-64.2). Seven of the 15 patients received androgen deprivation therapy (ADT) started after HIFU failure, interrupted before 11C choline PET and radiotherapy. Median prescribed dose was 71.4 Gy (range: 71.4-74.2 Gy) in 28 fractions. No radiation related major upper gastrointestinal (GI), rectal and GU toxicity were experienced. GU, acute grade 1 and grade 2 toxicities were recorded in 7/15 and 4/15 respectively; bowel acute grade 1 and grade 2 toxicities in 4/15 and 1/15; rectal acute grade 1 and grade 2 toxicities in 3/15 and 2/15 respectively. No grade 3 or greater acute or late toxicities occurred. Biochemical control was assessed in 12/15 (80%) patients. With a median follow up of 12 months, three out of 15 patients, with biochemical relapse, showed lymph-nodal recurrence. Our early clinical results and biochemical data confirm the feasibility and show a good tolerance of the 11C choline PET guided salvage radiation therapy after HIFU failure. The findings of low acute toxicity is encouraging, but longer follow-up is needed to assess late toxicity and definitive outcomes.

Invasion of the great vessels or atrium predicts worse prognosis in thymic carcinoma

PurposeWe evaluated treatment outcomes of thymic carcinomas to determine prognostic factors for survival.Materials and MethodsBetween May 1988 and May 2009, 41 patients had pathologic diagnosis of thymic carcinoma in Seoul National University Hospital, Seoul, Korea. Of these, 40 patients were followed up to 188 months after treatment. The mean age of all patients was 58.3 years and male to female ratio was 23 to 17.ResultsAmong 30 patients who underwent surgical resection, 26 achieved R0 resection and postoperative radiotherapy (PORT) was performed in 22 patients (73%). Various chemotherapeutic regimens were given with local treatment modalities, surgery and/or radiotherapy, in 12 patients. The 5-year locoregional control (LRC), distant metastasis-free survival, progression-free survival (PFS), and overall survival were 79.4%, 53.0%, 42.6%, and 63.6%, respectively. Patients with Masaoka stage I or II showed excellent prognosis of 5-year PFS around 90%. In advanced stages, invasion of the great vessels or atrium by thymic carcinomas was negative prognostic factor for PFS in univariate analysis. Lymph node involvement was statistically significant factor for LRC and PFS. Local or regional recurrence was infrequent after surgical resection followed by PORT, while distant metastasis was the major component of treatment failure.ConclusionComplete resection followed by PORT provided remarkable local control without severe acute toxicities in patients with stage II and favorable stage III thymic carcinoma. Invasion of the great vessels or atrium was statistically significant prognostic factor for PFS.

Accelerated intensity-modulated radiotherapy plus temozolomide in patients with glioblastoma: a phase I dose-escalation study (ISIDE-BT-1)

We performed a dose-escalation trial to determine the maximum tolerated dose (MTD) of intensity-modulated radiotherapy (IMRT) with standard concurrent and sequential-dose temozolomide (TMZ) in patients with glioblastoma multiforme. Histologically proven glioblastoma patients underwent IMRT dose escalation. IMRT was delivered over 5 weeks with the simultaneous integrated boost (SIB) technique to the two planning target volumes (PTVs) defined by adding 5-mm margin to the respective clinical target volumes (CTVs). CTV1 was the tumor bed plus the enhancing lesion with 10-mm margin; CTV2 was the area of perifocal edema with 20-mm margin. Only the PTV1 dose was escalated (planned dose escalation: 60, 62.5, 65, 67.5, 70 Gy) while the PTV2 dose remained the same (45 Gy). Forty consecutive glioblastoma patients were treated. While no dose-limiting toxicity (DLT) was recorded during the dose escalation up to 67.5/2.7 Gy, two out of the first six consecutively enrolled patients on the highest dose level (70/2.8 Gy) experienced a DLT, and therefore a cohort expansion was required. 3/14 patients experienced a DLT on the highest planned dose level, and therefore the MTD was not exceeded. After a median follow-up time of 25 months no grade >2 late neurological toxicity was recorded. By using a SIB IMRT technique, a radiation dose of 70 Gy in 25 fractions (biological effective dose--BED--of 92.8 Gy) can be delivered with concurrent and sequential standard dose TMZ, without unacceptable acute toxicity in patients with glioblastoma.

Reduced-intensity conditioning for allogeneic stem cell transplant in primary immune deficiencies

Conventional myeloablative conditioning regimens prior to hematopoietic cell transplantation (HCT) are associated with significant transplant-related morbidity and mortality in children affected by primary immunodeficiency disorders. Reduced-intensity conditioning regimens have been extensively used without severe acute toxicity in patients with pre-HCT comorbidities, with the additional advantage of reducing or avoiding long-term sequelae such as infertility and growth retardation. Compared with myeloablative HCT, reduced-intensity conditioning regimens are associated with an increased incidence of mixed donor chimerism and graft rejection. While mixed donor engraftment is likely to correct the phenotypic expression of most children with primary immunodeficiency disorders, the use of donor lymphocyte infusion to increase donor chimerism or second HCT procedures may be required in some cases. Here we discuss the most recent data on the use of different reduced-intensity conditioning protocols in children with primary immunodeficiency disorders, highlighting significant clinical lessons and areas that need additional study.

Comparison of acute toxicity in patients treated with a 4-field box or IMRT to deliver elective pelvic nodal irradiation for localized high-risk prostate cancer.

69 Background: To deliver elective pelvic nodal irradiation (EPNI), a 4-field box (4FB) has been a common technique. More recently, there are increasing reports of using IMRT to deliver EPNI. Even though studies show a clear dosimetric benefit to bowel and bladder, there is a lack of good data demonstrating decreased toxicity with the use of IMRT in this setting. Methods: From 2004-2010, 230 patients with localized high risk prostate cancer were enrolled into 3 sequential prospective phase I/II trials of delivering EPNI (45 Gy) along with a concomitant hypofractionated IMRT boost to the prostate (67.5 Gy total) in 25 fractions over 5 weeks time. All patients were to receive 3 years of adjuvant androgen deprivation. During the accrual period, the method used to deliver the EPNI portion of the treatment changed as new literature emerged about target volumes for EPNI. The 3 methods used to deliver EPNI in this large cohort were 1) 4FB, 2) IMRT with 2cm CTV margins around the pelvic vessels as suggested by Shih et al (IMRT-Shih), and 3) IMRT with nodal volumes as suggested by RTOG (IMRT-RTOG). Common Terminology Criteria for Adverse Events v3.0 was used to assess acute toxicity prospectively during treatment and then at 3 months. Results: For EPNI, 94 patients were treated with a 4FB, 53 were treated with IMRT-Shih, and 83 were treated with IMRT-RTOG. There were no acute grade 3 GI toxicities. Patients in the 4FB group had higher rates of acute grade ≥ 2 proctitis compared to the IMRT-Shih and IMRT-RTOG groups (16.0% vs 2.0% vs 2.4%, p=0.0009). The 4FB group also had higher rates of grade ≥ 2 flatulence compared to the 2 other IMRT groups (17.0% vs 7.6% vs 0%, p<0.0001). With regards to acute GU toxicities, patients in the 4FB group had higher rates of grade ≥ 3 urinary frequency compared to the 2 other IMRT groups (5.3% vs 0% vs 0%, p=0.027). Conclusions: In this non-randomized comparison, IMRT resulted in statistically significant decreases in acute proctitis, flatulence, and urinary frequency when compared to a 4FB technique to deliver EPNI in localized high risk prostate cancer. Analysis for possible confounding factors will be performed.

152 Clinical prediction for acute toxicity in patients with locally advanced non-small cell lung cancer receiving concurrent chemoradiation

152 Clinical prediction for acute toxicity in patients with locally advanced non-small cell lung cancer receiving concurrent chemoradiation

Prophylactic Percutaneous Endoscopic Gastrostomy in Patients With Advanced Head and Neck Tumors Treated by Combined Chemoradiotherapy

Context Few studies have evaluated outcomes of combined chemoradiotherapy for Stage III–IV head and neck squamous cell carcinoma in terms of the use of nutritional support by means of percutaneous endoscopic gastrostomy (PEG). Objectives To compare nutritional status and treatment interruption because of acute toxicity in patients with advanced head and neck tumors who were treated by combined chemoradiotherapy and received or did not receive prophylactic PEG tubes. Methods This was a retrospective study that evaluated data obtained from a cancer center in Montpellier, France. A total of 139 consecutive patients treated for Stage III–IV head and neck squamous cell carcinoma from January 1, 1998 to June 30, 2003 were evaluated in terms of nutritional status before and after therapy, treatment interruption because of toxicity, and duration of hospitalization. Results Seventy-eight of the 139 patients (58%) did not receive prophylactic PEG feeding, and 61 patients (44%) received PEG feeding. Pretreatment nutritional status was worse in the PEG group. Compared with the initial nutritional status, nutritional status at the end of treatment was unchanged in the PEG group and much worse in the group that did not receive the PEG ( P < 0.05). Cumulative incidence of treatment interruption because of toxicity was significantly lower in the PEG group than in the no-PEG group (100 and 236 days of interruption, respectively, P = 0.03) and hospitalization was significantly shorter ( P = 0.003). Conclusion Prophylactic PEG sustains nutritional status and reduces the cumulative incidence of treatment interruption caused by toxicity and duration of hospitalization. A randomized study is warranted to validate these results.

Nucleotide Excision Repair Gene Polymorphisms May Predict Acute Toxicity in Patients Treated with Chemoradiotherapy for Bladder Cancer

Platinum-based chemoradiotherapy (CRT) as bladder conservation therapy has shown promising results for muscle-invasive bladder cancer. However, treatment-related toxicity remains a major consideration in therapeutic planning. Some common polymorphisms in genes involved in DNA repair (encoding enzymes that repair DNA damaged by platinum agents and ionizing radiation) are reported to result in modulation of the repair capacity. We investigated associations between functional genetic polymorphisms involved in DNA repair and acute toxicity of CRT to determine the predictive value of these polymorphisms for toxicity. The study group comprised of 101 bladder cancer patients treated with platinum-based CRT, and seven polymorphisms in XPC (Lys939Gln, rs2228001), XPD (Lys751Gln, rs13181), XPG (Asp1104His, rs17655), XRCC1 (Arg399Gln, rs25487), XRCC3 (Thr241Met, rs861539), TP53 (Arg72Pro, rs1042522) and MDM2 (SNP309, T>G, rs2279744) were genotyped. More than two total variant alleles in nucleotide excision repair genes, including XPC, XPD and XPG, were significantly associated with grade 3 or 4 neutropenia (adjusted odds ratio [aOR]: 6.8; 95% CI: 2.0-26; p = 0.0026). There were no significant associations between any genotypes and grade 2 or greater nausea/vomiting or diarrhea. Any grade 3 or 4 hematological toxicity was significantly associated with the Gln/Gln or Lys/Gln + Gln/Gln genotypes of XPC compared with Lys/Lys (aOR: 10; 95% CI: 2.0-65; p = 0.0070 or aOR: 6.3; 95% CI: 1.9-29; p = 0.0069; respectively). These results suggest that nucleotide excision repair gene polymorphisms, especially in XPC, might potentially be predictive factors for acute toxicity of CRT for bladder cancer, helping individual patient selection for bladder conservation therapy. However, further studies with larger sample sizes are needed to draw final conclusions.

Impact of 3D vs. Intensity Modulated Radiation Therapy on Acute Toxicities in Patients Treated for Cervical Cancer

Impact of 3D vs. Intensity Modulated Radiation Therapy on Acute Toxicities in Patients Treated for Cervical Cancer

Abstract LB-213: Plasma soluble VEGFR1 is a potential dual biomarker of response and toxicity for bevacizumab with chemoradiation in locally advanced rectal cancer

Abstract We explored plasma and urinary concentration of four members of the vascular endothelial growth factor (VEGF) family as potential response and toxicity biomarker of bevacizumab with neoadjuvant chemoradiation in patients with localized rectal cancer. The levels of VEGF, placental growth factor (PlGF) and soluble VEGF receptors 1 and −2 (sVEGFR1 and sVEGFR2) were measured by multiplex array in plasma and urine at baseline and during treatment. Pre-treatment values and changes over time were analyzed as potential biomarkers of pathological response to treatment (evaluated histologically using ypT, Mandard and N scoring at surgery) as well as for all acute toxicities in patients with locally advanced rectal cancer treated prospectively from 2002 to 2008 with bevacizumab, 5-fluorouracil and radiation therapy prior to surgery in a phase I/II trial (N=32 patients). Of all biomarkers, the pretreatment plasma sVEGFR1 - an endogenous blocker of VEGF and a factor linked with “vascular normalization” - was strikingly associated with both tumor regression and with the number of adverse events after preoperative (neoadjuvant) bevacizumab and chemoradiation. Thus, plasma sVEGFR1 is a strong candidate as the first biomarker to stratify patients for bevacizumab therapy. Therefore, future studies of bevacizumab and/or cytotoxics should be further explore sVEGFR1 as biomarker in neoadjuvant setting as well as in metastatic disease. This study was partially supported by NIH grants R21-CA99237, P01-CA80124, R01-CA115767, R01-CA85140, R01-CA126642 and Federal Share/NCI Proton Beam Program Income grants, and by the National Foundation for Cancer Research. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-213.

Generation of donor natural killer cells from CD34+ progenitor cells and subsequent infusion after HLA-mismatched allogeneic hematopoietic cell transplantation: a feasibility study

Post transplant infusion of donor-type natural killer (NK) cells has been shown to have an anti-leukemia-enhancing effect without evoking GVHD in murine hematopoietic cell transplantation (HCT) models. Here, we tested 14 patients (age, 23-65 years), 12 with acute leukemia and 2 with myelodysplastic syndrome, who underwent HLA-mismatched HCT and subsequently received donor NK cell infusions. Cell donors (age, 16-51 years), comprising seven siblings, five offspring, and two mothers of the patients, underwent growth factor-mobilized leukapheresis for 3-5 days. Cells collected on the first 2-4 days were used for HCT, whereas those collected on the last day were CD34 selected by magnetic-activated cell sorting (median, 2.22 x 10(6) cells/kg; range, 0.29-5.66). Donor NK cells were generated from the CD34(+) cells by ex vivo cell culture over a 6-week period (median, 9.28 x 10(6) cells/kg; range, 0.33-24.50; CD122/CD56(+) 64%; CD3(+) 1.0%; and viability 88%). There were no signs of acute toxicity in patients infused with these cells 6-7 weeks post transplant. Overall, one and five patients developed acute and chronic GVHD during post transplant period, respectively. These results showed that clinical-grade donor NK cell production from CD34(+) cells is feasible.