Risk factors of radiation pneumonitis in patients with NSCLC treated with concomitant chemoradiotherapy--Are we underestimating diabetes?--Turkish oncology group (TOG)/Lung cancer study group.

INTRODUCTION: To evaluate the clinical and dosimetric parameters that increase the risk of radiation pneumonitis (RP) in locally advanced non-small cell lung cancer (NSCLC) patients treated with concomitant chemoradiotherapy of nationwide multicentric data analysis. METHODS: All data of 268 patients who underwent definitive chemoradiotherapy were retrospectively collected from eight institutes participating in this study. Patient, tumor and treatment-related factors and dosimetric parameters were analyzed for grade ≥2 RP. The toxicity scoring system of The Radiation Therapy Oncology Group used for grading the severity of pneumonitis. A relationship with the risk of RP with potential predictive factors were evaluated by univariate and multivariate analyses. A recursive partition analysis (RPA) was applied to stratify patients according to the risk of developing RP. RESULTS: There were 90 (33.6%) patients who had grade ≥2 RP. The median time to pneumonitis after treatment was 4 months (range:1-6 months). In univariate analysis, diabetes mellitus (DM), use of cisplatin/etoposide, total and daily radiotherapy (RT) fraction dose, the planning target volume (PTV) size, mean lung dose, V5, V10 and RT technique were associated with the development of pneumonitis. In multivariate analysis, only DM (P = 0.008) was found to be independent risk factors for RP. According to RPA, the risk of developing RP was highest in patients with DM. CONCLUSIONS: In our study, besides the known dosimetric factors, DM was found to be the most important risk factor causing RP development in multivariate analysis and RPA. The risk is tripled compared to patients without DM.

Circulating gelatinases are not prognostic of treatment response and survival in locally advanced rectal cancer patients undergoing preoperative chemoradiotherapy.

PURPOSE: To investigate whether the serum levels of matrix metalloproteinases (MMPs) are predictive on treatment response and survival in locally advanced rectal cancer (LARC) patients undergoing preoperative chemoradiotherapy. PATIENTS AND METHODS: Serum MMP-2 and MMP-9 was analyzed by enzyme-linked immunosorbent assay and obtained before, midway, and 1-month after the end of preoperative radiotherapy treatment. The prognostic significance of serum MMP-2 and MMP-9 levels and their association with other pathological findings for LARC patients were evaluated. RESULTS: Serum levels of MMP-2 or MMP-9 were found to decrease with increasing clinical stage and negative correlation was statistically significant (P < 0.05). There was no statistically significant difference in tumor response and survival between the low and high MMP-2 and MMP-9 groups. MMP-2 and MMP-9 were not correlated with local-regional recurrence. CONCLUSIONS: We propose that serum levels of MMP-2 and MMP-9 are not predictive on treatment response and survival in LARC patients.

Intensity-Modulated Radiation Therapy Improves the Target Coverage Over 3-D Planning While Meeting Lung Tolerance Doses for All Patients With Malignant Pleural Mesothelioma.

PURPOSE: To investigate high conformality on target coverage and the ability on creating strict lung dose limitation of intensity-modulated radiation therapy in malignant pleural mesothelioma. PATIENTS AND METHODS: Twenty-four radiation therapy plannings were evaluated and compared with dosimetric outcomes of conformal radiation therapy and intensity-modulated radiation therapy. Hemithoracal radiation therapy was performed on 12 patients with a fraction of 1.8 Gy to a total dose of 50.4 Gy. All organs at risk were contoured. Radiotherapy plannings were differed according to the technique; conformal radiation therapy was planned with conventionally combined photon-electron fields, and intensity-modulated radiation therapy was planned with 7 to 9 radiation beam angles optimized in inverse planning. Strict dose-volume constraints were applied. RESULTS: Intensity-modulated radiation therapy was statistically superior in target coverage and dose homogeneity (intensity-modulated radiation therapy-planning target volume 95 mean 100%; 3-dimensional conformal radiation therapy-planning target volume 95 mean 71.29%, P = .0001; intensity-modulated radiation therapy-planning target volume 105 mean 11.14%; 3-dimensional conformal radiation therapy-planning target volume 105 mean 35.69%, P = .001). The dosimetric results of the remaining lung was below the limitations on intensity-modulated radiation therapy planning data (intensity-modulated radiation therapy-lung mean dose mean 7.5 [range: 5.6%-8.5%]; intensity-modulated radiation therapy-lung V5 mean 55.55% [range: 47%-59.9%]; intensity-modulated radiation therapy-lung V20 mean 4.5% [range: 0.5%-9.5%]; intensity-modulated radiation therapy-lung V13 mean 13.43% [range: 4.2%-22.9%]). CONCLUSION: With a complex and large target volume of malignant pleural mesothelioma, intensity-modulated radiation therapy has the ability to deliver efficient tumoricidal radiation dose within the safe dose limits of the remaining lung tissue.

Definitive chemoradiotherapy in Stage III nonsmall cell lung cancer: Turkey experience.

AIM: Concurrent chemoradiotherapy (CRT) is the standard therapy for patients with unresectable Stage III nonsmall cell lung cancer (NSCLC). The aim of this study was to assess the efficacy and safety of concurrent CRT in unresectable Stage III NSCLC in Turkey. PATIENTS AND METHODS: The study included 82 patients with histologically proven unresectable Stage III NSCLC, Eastern Cooperative Oncology Group performance status 0-1, who received concurrent CRT in two different referral centers. Treatment consisted of two cycles of cisplatin at 50 mg/m 2 on days 1, 8, 29, and 36 and etoposide 50 mg/m 2 between days 1 and 5, 29-33 and concurrent radiotherapy administered once daily, 1.8-2.0 Gy per fraction, at a total dose of 60-66 Gy. RESULTS: The stages of the patients were Stage IIIA in 39 (47.5%) and IIIB in 43 (52.5%) patients. Complete and partial responses were achieved in 15 (18.2%) and 31 (37.8%) of the patients, respectively. Twenty-eight (34.2%) patients had stable disease and 8 (9.8) had progressive disease. Forty-one (50%) patients recurred during follow-up. The primary site of recurrence was as distant metastasis in 19 (23.2%) patients. Median overall survival (OS) was 20 months (95% confidence interval; 12.9-27.09 months), 3 and 4 years survivals were 27.9% and 20.9%, respectively. Median progression-free survival (PFS) was 9 months, 3 and 4 years PFSs were 20.1% and 16.1%. Myelosuppression was the most common toxicity. In 15 (19.2%) patients grade 2-3 lung toxicity and in seven (8.5%) patients' grade 2-3 dysphagia were reported. CONCLUSION: Concurrent CRT with cisplatin and etoposide schedule is a well-tolerated regimen with acceptable toxicity profile and survival rates in patients with unresectable Stage IIIA/IIIB NSCLC. Median survival and OS results were consistent with the literature.

Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma.

BACKGROUND: We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC). METHODS: A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013. RESULTS: Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered. CONCLUSIONS: Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection.

Radical Oncological Surgery and Adjuvan Therapy in Non- Small Cell Lung Cancer Patients over 70 years of Age.

BACKGROUND: The incidence of lung cancer increases with age. Approximately 50% of non-small cell lung cancer (NSCLC) patients are over 70 years old. Because of the increasing elderly population, treatment approaches in this age group continue to be studied similar to groups of young people. MATERIALS AND METHODS: In the current study, 26 patients who underwent radical surgery and adjuvan chemoradiation at Ataturk Chest Diseases and Chest Surgery Training and Research Hospital were evaluated retrospectively. RESULTS: Of 21 patients (81%) were male and the average age was 74.4. Lobectomy was performed in 18 cases, pneumonectomy in 3, sleeve lobectomy in 3 and bilobectomy in 2. There was no perioperative or early period mortality. Overall survival was 24.5 months. CONCLUSIONS: From our study, lung cancer surgery and adjuvant therapy can be performed safely with low morbidity in the elderly.

PET-CT guided curative conformal radiation therapy in limited stage small cell lung cancer.

BACKGROUND: The prognosis of small cell lung cancer (SCLC) has been improving with the advances in diagnostic and therapeutic modalities. Positron emission tomography/computed tomography (FDG-PET/CT) which has been studied in non-small cell lung cancer (NSCLC) for a long time, and it has only recently been applied to SCLC. Therefore we sought to observe firstly the prognostic importance of the FDG uptake in limited disease small cell lung cancer (LD-SCLC) patients and secondly the clinical outcomes and toxicity profiles of LD-SCLC patients treated with conformal radiation therapy (RT) using FDG-PET/CT simulation. METHODS: Between 2009 and 2011, 33 LD-SCLC patients with LD-SCLC underwent disease staging using FDG-PET/CT conformal RT. Thoracic radiation was administered at a daily fraction of 2 Gy. Total dose was prescribed according to the treatment protocol such as, concurrent or sequential chemotherapy and in some patients according to the response of CT. All patients underwent chemotherapy. Survival was estimated using the Kaplan-Meier method. RESULTS: The median age of the patients was 58 years (range, 38-77 years). The median follow-up time was 20 months (range, 6.6-47.6 months). The 3-year overall survival (OS) and locoregional control rates were 23% and 48%, respectively. CONCLUSIONS: There are few studies examining the impact of PET-CT and the prognostic significance of FDG-uptake on outcomes in patients with LD-SCLC. Higher RT doses in response to higher FDG uptake may be safely applied for the purpose of locoregional control.

Estimating radiation therapy toxicity and tolerability with comprehensive assessment parameters in geriatric cancer patients.

Cancer prevalance and incidence is increasing with aging of populations and age is a critical factor in decision-making for anti-cancer treatment. However it is believed that chronological age is not enough to guide management in elderly cancer patients. Multidisciplinary evaluation and comprehensive geriatric assessment has gained importance regarding the treatment selection especially for definitive anti-cancer therapy recently. We here aimed to analyse the effect of the comprehensive geriatric assessment parameters on radiotherapy toxicity and tolerability in a series of geriatric cancer patients in Turkey.

Is there any impact of PET/CT on radiotherapy planning in rectal cancer patients undergoing preoperative IMRT?

BACKGROUND/AIM: To investigate the effect of positron emission tomography-computed tomography (PET/CT)-based contouring on dosimetric parameters in rectal cancer patients undergoing preoperative intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: Preoperative radiation therapy plans with conformal radiotherapy (CRT) or IMRT were created and examined according to the CT- and PET/CT-based contouring of 20 rectal cancer patients, retrospectively. RESULTS: The target volumes delineated with PET/CT were significantlylarger than the volumes created by CT (P= 0.043). Dose delivered to 98% of the planning target volume was high in IMRT planning contouring with CT and PET/CT compared with CRT planning, but the difference was not statistically significant (P = 0.056). Percent volumes receiving 105% of dose and 110% of dose were low in IMRT planning when compared with CRT (P < 0.0001 and P = 0.044, respectively). The volumes receiving 45 Gy for the small intestine, femur heads, and bladder and the maximum dose received by the bladder were significantly lower in IMRT. CONCLUSION: We showed that the target volumes created with PET/CT are significantly larger than the target volumes created with CT and that IMRT provides lower radiation exposure to the tumor-free tissues compared to the CRT planning. The dosimetric results primarily favor IMRT planning in rectal cancer patients and consequently present the significant alteration in target volumes.

The clinical and pathological features of 133 colorectal cancer patients with brain metastasis: a multicenter retrospective analysis of the Gastrointestinal Tumors Working Committee of the Turkish Oncology Group (TOG).

Brain metastasis in colorectal cancer is highly rare. In the present study, we aimed to determine the frequency of brain metastasis in colorectal cancer patients and to establish prognostic characteristics of colorectal cancer patients with brain metastasis. In this cross-sectional study, the medical files of colorectal cancer patients with brain metastases who were definitely diagnosed by histopathologically were retrospectively reviewed. Brain metastasis was detected in 2.7 % (n = 133) of 4,864 colorectal cancer patients. The majority of cases were male (53 %), older than 65 years (59 %), with rectum cancer (56 %), a poorly differentiated tumor (70 %); had adenocarcinoma histology (97 %), and metachronous metastasis (86 %); received chemotherapy at least once for metastatic disease before brain metastasis developed (72 %), had progression with lung metastasis before (51 %), and 26 % (n = 31) of patients with extracranial disease at time the diagnosis of brain metastasis had both lung and bone metastases. The mean follow-up duration was 51 months (range 5-92), and the mean survival was 25.8 months (95 % CI 20.4-29.3). Overall survival rates were 81 % in the first year, 42.3 % in the third year, and 15.7 % in the fifth year. In multiple variable analysis, the most important independent risk factor for overall survival was determined as the presence of lung metastasis (HR 1.43, 95 % CI 1.27-4.14; P = 0.012). Brain metastasis develops late in the period of colorectal cancer and prognosis in these patients is poor. However, early screening of brain metastases in patients with lung metastasis may improve survival outcomes with new treatment modalities.

Role of triamcinolone in radiation enteritis management.

AIM: To investigate the role of triamcinolone in the management of acute and chronic enteritis caused by pelvic radiotherapy. METHODS: Twenty-eight patients with rectum adenocarcinoma or endometrium adenocarcinoma were studied. We compared the results of 14 patients treated with injected triamcinolone acetonide (TA) with those of 14 patients who were not treated with TA. For the TA group, 40 mg of TA was injected intramuscularly on the 1(st), 11(th) and 21(st) d of radiotherapy; the control group received no injections. All of the study participants had a median age of 65 years, had undergone postoperative radiotherapy and were evaluated weekly using Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer Acute Morbidity Score Criteria, and complete blood counts for every 10 d. RESULTS: Triamcinolone was found to effectively prevent and treat radiation-induced acute gastrointestinal (enteritis) and genitourinary (cystitis) side effects (P = 0.022 and P = 0.023). For the lower GI side effect follow up, 11 patients in the control group had Grade 2 toxicity and 3 patients had Grade 1 toxicity. In the TA group, 5 patients had Grade 2 toxicity and 9 patients had Grade 1 toxicity. For the genitourinary system side effect follow up, 4 patients had Grade 2 toxicity and 6 patients had Grade 1 toxicity. Additionally, 2 patients had Grade 2 toxicity and 2 patients had Grade 1 toxicity. The neutrophil counts did not differ between the TA group and the control group. There was no meaningful difference between age groups and primary cancers. At the 12th mo of follow up, there were no differences between groups for chronic side effects. CONCLUSION: Triamcinolone is a moderately potent steroid, that is inexpensive and has a good safety profile. It would be beneficial for reducing medical expenses related to treatment of radiation induced enteritis.

High FDG uptake predicts poorer survival in locally advanced nonsmall cell lung cancer patients undergoing curative radiotherapy, independently of tumor size.

OBJECTIVES: Despite radical radiotherapy and chemotherapy (CT), the prognosis of locally advanced nonsmall cell lung cancer (NSCLC) is poor. New prognostic indicators are being looked forward to improve the survival. [18F]-fluorodeoxyglucose (FDG) uptake on PET/CT has been observed as a prognostic marker mainly in early-stage disease. Our aim was to examine the prognostic value of FDG uptake in locally advanced NSCLC. MATERIALS AND METHODS: Between 2009 and 2011, 103 NSCLC patients underwent disease staging using FDG PET/CT before conformal radiotherapy. Thoracic radiation was administered at a daily fraction of 2 Gy. Total dose was prescribed according to the tumor response against CT. All patients underwent CT. Survival was estimated using the Kaplan-Meier method. RESULTS: The median age of the patients was 59 years (range 39-83). The median follow-up time was 22.63 months (range 6-48.03 months). There was a statistically significant difference in overall survival (OS) between the low (<10.7) and high (≥10.7) standardized uptake value (SUVmax) groups (p = 0.006) on univariate analysis (3-year OS was 42% in the low (<10.7) and 23% in the high (≥10.7) SUVmax groups). On multivariate analysis with determining tumor size, tumor SUVmax provided additional significant prognostic information on OS (HR 1.046; 95 % CI 1.009-1.085, p = 0.015). CONCLUSIONS: FDG uptake has predictive value in locally advanced NSCLC, independently of tumor size.

Clinical Features and Prognostic Factors of Hodgkin's Lymphoma: A Single Center Experience.

BACKGROUND: Hodgkin's lymphoma (HL) is a B cell lymphoma characterized by the presence of Reed-Sternberg cells. HL comprises 1% of all cancer cases and 14% of all lymphoma cases. AIMS: We designed a retrospective study to investigate the clinical features and prognostic factors of HL patients diagnosed at an experienced oncology centre. STUDY DESIGN: Retrospective study. METHODS: Demographic characteristics, histopathological and clinical features, treatment modalities and response to treatment were obtained from hospital records. Dates of initial diagnosis, remission and relapse, last visit and death were recorded for survival analyses. RESULTS: We analysed data of 391 HL patients (61% male, 39% female; mean age 35.7±15.1 years). The most common classical HL histological subtype was nodular sclerosing HL (NSHL) (42.7%). The most common stage was II 50.4%. The most common chemotherapy regimen was doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) (70.6%). Five and 10-year survival rates were 90% and 84%, respectively. Early-stage patients with good prognostic factors had better overall and relapse-free survival rates. The presence of "B" symptoms, albumin level, Eastern Cooperative Oncology Group (ECOG) performance score, and LDH were prognostic factors that affect the survival in both univariate and multivariate analyses. CONCLUSION: This is the first study that demonstrates the demographic, clinical and prognostic features of HL patients in Turkey, and provides a general picture of the HL patients in our country.

Long-term complications in Hodgkin's lymphoma survivors.

Background. Although patients with Hodgkin's lymphoma (HL) achieve prolonged survival, long-term complications are a major cause of morbidity and mortality among long-term survivors of HL. Methods. We retrospectively evaluated long-term complications in 336 HL survivors treated between January 1990 and January 2006 at the Department of Medical Oncology of the Hacettepe University Institute of Oncology who were >16 years old at presentation. All patients were regularly followed up every 3 months for the first 2 years after complete response, biannually for 3 years, and annually after 5 years. Results. Median follow-up was 8.5 years. The mean age (±SD) of the patients at the time of diagnosis was 35.7 ± 13.1 years. The male to female ratio was 61%/39%. During follow-up, 29 second malignancies (8.6%) were diagnosed in 28 patients with HL; 22 were solid tumors and 7 were hematological malignancies. Forty-seven (14.0%) of all patients with HL were found to have thyroid abnormalities. During follow-up, 54 (16.1%) patients developed cardiovascular complications. Overall, 29 (8.6%) patients developed late pulmonary toxicities. The cumulative number of chronic viral infections was 13 (3.9%). Conclusions. Long-term survivors of HL need to be properly followed up not only for disease control but also for evaluation of possible late morbidities to minimize the consequences.

Comparison of intracavitary brachytherapy and stereotactic body radiotherapy dose distribution for cervical cancer.

PURPOSE: To compare the dose distribution characteristics of stereotactic body radiotherapy (SBRT) with intracavitary high-dose-rate (HDR) brachytherapy in patients with cervical carcinoma. METHODS AND MATERIALS: HDR intracavitary brachytherapy treatment plans for 11 women with cervical carcinoma were evaluated in this analysis. The total HDR brachytherapy dose was 28Gy given in four fractions. HDR brachytherapy was delivered with the microSelectron HDR therapy unit (Nucletron B. V., Veenendaal, The Netherlands). SBRT plans for each patient were generated with MultiPlan for CyberKnife Robotic Radiosurgery System (Accuray Inc., Sunnyvale, CA). The dose distributions, dose-volume histograms, and maximum dose points of the target and critical organs were recorded for both plans. RESULTS: SBRT yielded significantly better target coverage; the median target coverage for the 100% isodose line was 50.7% for HDR brachytherapy plans, whereas it was 99.1% for SBRT plans. The dose distributions for critical organs were similar in both types of plans. The exceptions were the 25% isodose being significantly better in brachytherapy plans for rectum, and the 100% isodose exposure being higher in brachytherapy plans for rectum, bladder, and sigmoid colon. Some significant differences were also found in maximum doses received by a 2-cc volume of bladder in favor of SBRT plans. In addition, maximum bone marrow doses were significantly higher in SBRT plans. CONCLUSION: SBRT plans achieved better target coverage and better dose distributions to critical organs except bone marrow compared with HDR brachytherapy plans in patients with locally advanced cervical cancer.

Incidence of hypothyroidism after radiotherapy for nasopharyngeal carcinoma.

OBJECTIVES: The thyroid gland is frequently affected by radiotherapy applied for the treatment of head and neck tumors. Hypothyroidism is observed as a late side effect of radiotherapy, especially seen in the patients who have surgery in the treatment procedure. METHODS: We evaluated the radiation-induced hypothyroidism for a selected type of head and neck cancer- nasopharyngeal cancer (NPC)-which does not include surgery involving the thyroid gland in the treatment. RESULTS: We observed 12 patients (14%) who developed hypothyroidism, two of which were subclinical hypothyroidism. The patients with hypothyroidism were statistically significantly younger than the euthyroid patients, but there were no statistically significant differences among the two groups in disease stages, radiotherapy neck doses, and gender. CONCLUSIONS: We recommend life-long TSH screening after RT to the neck owing to the incidence of RTinduced hypothyroidism and the importance of early thyroid hormone replacement therapy in patients becoming hypothyroid for maintaining optimal quality of life.

Paraganglioma in sella.

We report a very rare case of a paraganglioma arising from sellar and suprasellar region which has been treated with radiotherapy following multiple surgeries.