Cem Onal

Prevention of acute radiation-induced esophagitis with glutamine in non-small cell lung cancer patients treated with radiotherapy: Evaluation of clinical and dosimetric parameters

BACKGROUND The purpose of this study was to evaluate the efficacy of oral glutamine in the prevention of acute radiation-induced esophagitis (ARIE) and weight loss in lung carcinoma patients, and to determine the clinical/dosimetric predictors of ARIE. PATIENTS AND METHODS Data from 41 patients with stage III lung carcinoma treated with thoracic irradiation were retrospectively analyzed. Twenty-two patients (53.6%) received prophylactic powdered glutamine in doses of 10g/8h. Prescribed radiation dose to planning target volume was 60Gy, in 30 fractions, 5 days/week. The primary endpoint included the ARIE incidence and its correlation with clinical/dosimetric factors relative to treatment with glutamine. RESULTS Glutamine was well tolerated. Grade 2 or 3 ARIE occurred in 20 (48.8%) of 41 patients: seven in the glutamine-supplemented group, and 13 in the glutamine-free group (p=0.002). All seven patients with grade 3 esophagitis were in the glutamine-free group (36.8% vs. 0%). Glutamine supplementation appeared to significantly delay ARIE onset for six days (22 days vs. 16 days; p=0.002). Glutamine-supplemented patients demonstrated a lower incidence of grade 2 or 3 ARIE (27.2%), and gained weight during radiotherapy (p=0.04). V55 was the only dosimetric parameter that correlated with the severity of ARIE in glutamine-free patients: a V55 of <35% had a 31% risk of ARIE grade 2 or 3, and the risk increased to 76% with a V55 of >or=35% (p=0.01). CONCLUSION This schedule and dosage of glutamine may be beneficial in the prevention of ARIE and weight loss in lung cancer patients undergoing thoracic irradiation.

Comparison of conventional and CT-based planning for intracavitary brachytherapy for cervical cancer: target volume coverage and organs at risk doses

BackgroundTo compare intracavitary brachytherapy (ICBT) planning methods for cervical cancer, based on either orthogonal radiographs (conventional plan) or CT sections (CT plan); the comparison focused on target volume coverage and dose volume analysis of organs at risk (OARs), by representing point doses defined by the International Commission on Radiation Units and Measurement (ICRU) and dose volume histograms (DVHs) from 3D planning.MethodsWe analyzed the dosimetric data for 62 conventional and CT-based ICBT plans. The gross tumor volume (GTV), clinical target volume (CTV) and organs at risk (OAR)s were contoured on the CT-plan. Point A and ICRU 38 rectal and bladder points were defined on reconstructed CT images.ResultsPatients were categorized on the basis of whether the >95% isodose line of the point-A prescription dose encompassed the CTV (group 1, n = 24) or not (group 2, n = 38). The mean GTV and CTV (8.1 cc and 20.6 cc) were smaller in group 1 than in group 2 (24.7 cc and 48.4 cc) (P < 0.001). The mean percentage of GTV and CTV coverage with the 7 Gy isodose was 93.1% and 88.2% for all patients, and decreased with increasing tumor size and stage. The mean D2 and D5 rectum doses were 1.66 and 1.42 times higher than the corresponding ICRU point doses and the mean D2 and D5 bladder doses were 1.51 and 1.28 times higher. The differences between the ICRU dose and the D2 and D5 doses were significantly higher in group 2 than in group 1 for the bladder, but not for the rectum.ConclusionThe CT-plan is superior to the conventional plan in target volume coverage and appropriate evaluation of OARs, as the conventional plan overestimates tumor doses and underestimates OAR doses.

Comparison of CT and PET-CT based planning of radiation therapy in locally advanced pancreatic carcinoma

BackgroundTo compare computed tomography (CT) with co-registered positron emission tomography-computed tomography (PET-CT) as the basis for delineating gross tumor volume (GTV) in unresectable, locally advanced pancreatic carcinoma (LAPC).MethodsFourteen patients with unresectable LAPC had both CT and PET images acquired. For each patient, two three-dimensional conformal plans were made using the CT and PET-CT fusion data sets. We analyzed differences in treatment plans and doses of radiation to primary tumors and critical organs.ResultsChanges in GTV delineation were necessary in 5 patients based on PET-CT information. In these patients, the average increase in GTV was 29.7%, due to the incorporation of additional lymph node metastases and extension of the primary tumor beyond that defined by CT. For all patients, the GTVCT versus GTVPET-CT was 92.5 ± 32.3 cm3 versus 104.5 ± 32.6 cm3 (p = 0.009). Toxicity analysis revealed no clinically significant differences between two plans with regard to doses to critical organs.ConclusionCo-registration of PET and CT information in unresectable LAPC may improve the delineation of GTV and theoretically reduce the likelihood of geographic misses.

Prognostic value of pretreatment 18F-fluorodeoxyglucose uptake in patients with cervical cancer treated with definitive chemoradiotherapy.

Objective We analyzed the correlation of 18F-fluorodeoxyglucose (FDG) uptake into primary tumors using the maximum standardized uptake value (SUVmax) and clinicopathological factors of disease. The impact of the pretreatment SUVmax of the primary tumor on survival was investigated. Materials and Methods The records of 149 patients with biopsy-proven cervical cancer treated with definitive chemoradiotherapy (ChRT) were reviewed. All patients underwent pretreatment FDG positron emission tomography with computed tomography, and posttherapy FDG positron emission tomography with computed tomography was performed within a median interval of 4.2 months (range, 3.0–11.2 months) after the completion of chemoradiotherapy. Results The mean SUVmax in patients with lymph node metastasis was significantly higher than that in patients without metastasis (19.7 ± 8.2 vs 16.4 ± 8.2, respectively; P = 0.01). A significant difference existed between tumor size (<4 vs ≥4 cm) and the primary tumor SUVmax (14.7 ± 6.6 vs 18.7 ± 8.5, respectively; P = 0.02). The primary tumor pretreatment SUVmax for patients with complete remission was significantly lower than that of patients with partial response or progressive disease (15.6 ± 5.7 vs 28.0 ± 9.9, respectively; P < 0.001). The relationship between primary tumor FDG uptake and survival was evaluated by the cutoff value determined by receiver operating characteristic curve analysis. The area under the curve was 0.901 (P < 0.001; 95% confidence interval, 0.848–0.954), and 15.6 was determined as the SUVmax cutoff value. The 4-year actuarial overall survival (OS) and disease-free survival for SUVmax of less than 15.6 compared with SUVmax of 15.6 or greater were 85% vs 34% (P < 0.001) and 80% vs 29%, respectively (P < 0.001). In multivariate analysis, age, SUVmax of 15.6 or greater, and lymph node metastasis were independent prognostic factors of OS, and International Federation of Gynecology and Obstetrics stage IIB or higher, SUVmax of 15.6 or greater, and lymph node metastasis were significant factors for disease-free survival. Conclusion The primary tumor pretreatment SUVmax is correlated with increased tumor size and lymph node involvement at diagnosis, how well the primary tumor responds to treatment, the likelihood of disease recurrence, and OS.

Prognostic value of gross tumor volume delineated by FDG-PET-CT based radiotherapy treatment planning in patients with locally advanced pancreatic cancer treated with chemoradiotherapy

BackgroundWe aimed to assess whether gross tumor volume (GTV) determined by fusion of contrast-enhanced computerized tomography (CT) and 18F-fluoro-deoxy-D-glucose positron emission tomography-CT (FDG-PET-CT) based radiotherapy planning could predict outcomes, namely overall survival (OS), local-regional progression-free survival (LRPFS), and progression-free survival (PFS) in cases with locally advanced pancreas cancer (LAPC) treated with definitive concurrent chemoradiotherapy.MethodsA total of 30 patients with histological proof of LAPC underwent 50.4 Gy (1.8 Gy/28 fractions) of radiotherapy concurrent with continuously infused 5-FU followed by 4 to 6 courses of maintenance gemcitabine. Target volume delineations were performed on FDG-PET-CT-based RTP. Patients were stratified into 2 groups: GTV lesser (GTVL) versus greater (GTVG) than cut off value determined by receiver operating characteristic (ROC) analysis, and compared in terms of OS, LRPFS and PFS.ResultsMedian GTV delineated according to the FDG-PET-CT data was 100.0 cm3. Cut off GTV value determined from ROC curves was 91.1 cm3. At a median follow up of 11.2 months, median OS, LRPFS and PFS for the entire population were 10.3, 7.8 and 5.7 months, respectively. Median OS, LRPFS and PFS for GTVL and GTVG cohorts were 16.3 vs. 9.5 (p = 0.005), 11.0 vs. 6.0 (p = 0.013), and 9.0 vs. 4.8 months (p = 0.008), respectively.ConclusionsThe superior OS, LRPFS and PFS observed in GTVL patients over GTVG ones suggests a potential for FDG-PET-CT-defined GTV size in predicting outcomes of LAPC patients treated with definitive C-CRT, which needs to be validated by further studies with larger cohorts.

Plasma citrulline levels predict intestinal toxicity in patients treated with pelvic radiotherapy.

Abstract Background. Radiotherapy (RT) for abdominal and pelvic malignancies often causes severe small bowel toxicity. Citrulline concentrations are known to decrease with intestinal failure. We thus evaluated the feasibility of plasma citrulline levels in predicting radiation-induced intestinal toxicity. Material and methods. Fifty-three patients (36 prostate cancer, 17 endometrial cancer) who received 45 Gy pelvic RT using conventional fractionation were prospectively evaluated. Patients with prostate cancer received an additional 25–30.6 Gy conformal boost. Plasma citrulline levels were assessed on day 0, mid- (week 3) and post-RT (week 8), and four months post-RT. Dose-volume histogram, citrulline concentration changes, and weekly intestinal toxicity scores were analyzed. Results. Mean age was 63 years (range: 43–81 years) and mean baseline citrulline concentration was 38.0 ± 10.1 μmol/l. Citrulline concentrations were significantly reduced at week 3 (27.4 ± 5.9 μmol/l; p < 0.0001), treatment end (29.9 ± 8.8 μmol/l; p < 0.0001), and four months post-treatment (34.3 ± 12.1; p = 0.01). The following factor pairs were significantly positively correlated: Citrulline concentration/mean bowel dose during, end of treatment, and four months post-RT; dose-volume parameters/citrulline change groups; cumulative mean radiation dose/intestinal toxicity at end and four months post-RT; citrulline changes/intestinal toxicity during and end of RT. Citrulline concentration changes significantly differed during treatment according to RTOG intestinal toxicity grades (p < 0.0001). Although the citrulline changes differed significantly within RTOG intestinal toxicity grades (p = 0.003), the difference between Grade 0 and Grade 1 did not differ significantly at the end of the treatment. At four months after RT, no significant differences were apparent. Conclusion. Citrulline-based assessment scores are objective and should be considered in measuring radiation-induced intestinal toxicity.

Comparison of rectal volume definition techniques and their influence on rectal toxicity in patients with prostate cancer treated with 3D conformal radiotherapy: a dose-volume analysis

BackgroundTo evaluate the impact of four different rectum contouring techniques and rectal toxicities in patients with treated with 3D conformal radiotherapy (3DCRT).MethodsClinical and dosimetric data were evaluated for 94 patients who received a total dose 3DCRT of 70 Gy, and rectal doses were compared in four different rectal contouring techniques: the prostate-containing CT sections (method 1); 1 cm above and below the planning target volume (PTV) (method 2); 110 mm starting from the anal verge (method 3); and from the anal verge to the sigmoid flexure (method 4). The percentage of rectal volume receiving RT doses (30–70 Gy) and minimum, mean rectal doses were assessed.ResultsMedian age was 69 years. Percentage of rectal volume receiving high doses (≥ 70 Gy) were higher with the techniques that contoured smaller rectal volumes. In methods 2 and 3, the percentage of rectal volume receiving ≥ 70 Gy was significantly higher in patients with than without rectal bleeding (method 2: 30.8% vs. 22.5%, respectively (p = 0.03); method 3: 26.9% vs. 18.1%, respectively (p = 0.006)). Mean rectal dose was significant predictor of rectal bleeding only in method 3 (48.8 Gy in patients with bleeding vs. 44.4 Gy in patients without bleeding; p = 0.02).ConclusionDifferent techniques of rectal contouring significantly influence the calculation of radiation doses to the rectum and the prediction of rectal toxicity. Rectal volume receiving higher doses (≥ 70 Gy) and mean rectal doses may significantly predict rectal bleeding for techniques contouring larger rectal volumes, as was in method 3.

Definitive Chemoradiation Therapy Following Surgical Resection or Radiosurgery Plus Whole-Brain Radiation Therapy in Non-Small Cell Lung Cancer Patients With Synchronous Solitary Brain Metastasis: A Curative Approach

PURPOSE/OBJECTIVES The aim of this study was to evaluate the impact of definitive thoracic chemoradiation therapy following surgery or stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT) on the outcomes of patients with non-small cell lung cancer (NSCLC) with synchronous solitary brain metastasis (SSBM). METHODS AND MATERIALS A total of 63 NSCLC patients with SSBM were retrospectively evaluated. Patients were staged using positron emission tomography-computed tomography in addition to conventional staging tools. Thoracic radiation therapy (TRT) with a total dose of 66 Gy in 2 Gy fractions was delivered along with 2 cycles of cisplatin-based chemotherapy following either surgery plus 30 Gy of WBRT (n=33) or SRS plus 30 Gy of WBRT (n=30) for BM. RESULTS Overall, the treatment was well tolerated. All patients received planned TRT, and 57 patients (90.5%) were also able to receive 2 cycles of chemotherapy. At a median follow-up of 25.3 months (7.1-52.1 months), the median months of overall, locoregional progression-free, neurological progression-free, and progression-free survival were 28.6, 17.7, 26.4, and 14.6, respectively. Both univariate and multivariate analyses revealed that patients with a T1-T2 thoracic disease burden (P=.001), a nodal stage of N0-N1 (P=.003), and no weight loss (P=.008) exhibited superior survival. CONCLUSIONS In the present series, surgical and radiosurgical treatments directed toward SSBM in NSCLC patients were equally effective. The similarities between the present survival outcomes and those reported in other studies for locally advanced NSCLC patients indicate the potentially curative role of definitive chemoradiation therapy for highly selected patients with SSBM.

Radiation recall pneumonitis caused by erlotinib after palliative definitive radiotherapy.

Background: Radiation recall pneumonitis (RRP) occurs in a previously irradiated field and is triggered by certain cytotoxic drugs, principally chemotherapeutic agents such as erlotinib. Erlotinib is a reversible epidermal growth factor receptor tyrosine kinase inhibitor (TKI) and is an effective second-line treatment for patients with advanced-stage non-squamous-cell lung cancer. Previously, only 2 cases of radiation recall after erlotinib treatment have been reported. Here, we report a case of RRP caused by treatment with erlotinib 4 months after palliative definitive hypofractionated radiation therapy (RT). Patient and Methods: A 58-year-old male patient with non-small cell lung cancer (adenocarcinoma) was treated with polychemotherapy, palliative RT (30 Gy in 10 fractions), and erlotinib thereafter. Results: Dosimetric analysis obtained from a 3-dimensional conformal RT planning system revealed that the volume of lung receiving at least 20 Gy (V20) was 21.2% and the mean lung dose was 12.7 Gy. These data indicate that systemic administration of a TKI, even after palliative RT, may lead to unexpected toxicity when the radiation field encompasses visceral organs. Conclusion: We conclude that the use of a TKI after RT may trigger radiation pneumonitis. Although evidence is limited, we advise clinicians to be cautious of RRP after erlotinib treatment.

Comparison of the protective effects of melatonin and amifostine on radiation-induced epiphyseal injury.

Purpose: We compared the effects of amifostine and melatonin in preventing radiation-induced epiphyseal growth plate injury in rats. Materials and methods: Four-week-old (65–85 g), growing male Sprague-Dawley rats were randomly assigned to receive radiation alone, at 25 Gy in three fractions (group R), or this dose of fractionated radiation proceeded by prophylactic amifostine 200 mg/kg i.p. (group A), melatonin 15 mg/kg i.p. (group M), or amifostine + melatonin (group AM). The right rear extremity of each animal was irradiated while the contralateral leg was shielded from radiation, as a control. Bone growth based on the length of the tibia, femur, and overall limb was calculated 6 weeks after the treatment. Results: In groups R, A, M, and AM, the mean growth loss (GL) for the overall limb was 56.9 ± 8.1%, 46.8 ± 7.7%, 36.6 ± 4.3%, and 38.5 ± 5.1%, respectively. The limb length discrepancies (LLD) in groups R, A, M, and AM were 13.8 ± 1.4%, 10.5 ± 0.3%, 7.4 ± 0.7%, and 8.8 ± 1.1%, respectively. Differences in LLD were significant between each treatment group and group R (range: p = 0.0001–0.001). Differences in either of mean GL and LLD were not significant between groups M and AM; however both of these groups had significantly less GL and LLD than group A. Conclusions: We observed a superior radioprotective function of melatonin over amifostine in preventing radiation-induced epiphyseal growth plate injury, without any increase in radioprotective effect by adding amifostine to melatonin.