Evaluation of Nutritional Status and Anxiety Levels in Patients Applying to the Radiation Oncology Outpatient Clinic during the COVID-19 Pandemic: Turkish Society for Radiation Oncology Group Study (TROD 12:02).

Cancer patients often face malnutrition, which negatively affects their response to cancer treatment. This study aims to analyze the effects of the COVID-19 pandemic on nutritional status and anxiety in cancer patients with different types and stages of cancer. This is a cross-sectional cohort study that includes 1,252 patients with varying cancer types from 17 radiation oncology centers. The nutritional risk scores (NRS-2002) and coronavirus anxiety scale (CAS) scores of all patients were measured. NRS-2002 ≥ 3 and CAS ≥ 5 were accepted as values at risk. Of all patients, 15.3% had NRS-2002 ≥ 3. Breast cancer was the most prevalent cancer type (24.5%) with the lowest risk of nutrition (4.9%, p < 0.001). Nutritional risk was significantly higher in patients with gastrointestinal cancer, head and neck cancer, and lung cancer (p < 0.005) and in patients with stage IV disease (p < 0.001). High anxiety levels (CAS ≥ 5) were significantly related to voluntary avoidance and clinical postponement of hospital visits due to the pandemic (p < 0.001), while clinical postponement was particularly frequent among patients with NRS-2002 < 3 (p = 0.0021). Fear and anxiety in cancer patients with COVID-19 cause hesitations in visiting hospitals, leading to disrupted primary and nutritional treatments. Thus, nutritional monitoring and treatment monitoring of cancer patients are crucial during and after radiotherapy.

Treatment outcomes of prostate cancer patients with Gleason score 8-10 treated with definitive radiotherapy : TROD 09-001 multi-institutional study.

PURPOSE: To validate the clinical outcomes and prognostic factors in prostate cancer (PCa) patients with Gleason score (GS) 8-10 disease treated with external beam radiotherapy (EBRT) + androgen deprivation therapy (ADT) in the modern era. METHODS: Institutional databases of biopsy proven 641 patients with GS 8-10 PCa treated between 2000 and 2015 were collected from 11 institutions. In this multi-institutional Turkish Radiation Oncology Group study, a standard database sheet was sent to each institution for patient enrollment. The inclusion criteria were, T1-T3N0M0 disease according to AJCC (American Joint Committee on Cancer) 2010 Staging System, no prior diagnosis of malignancy, at least 70 Gy total irradiation dose to prostate ± seminal vesicles delivered with either three-dimensional conformal RT or intensity-modulated RT and patients receiving ADT. RESULTS: The median follow-up time was 5.9 years (range 0.4-18.2 years); 5­year overall survival (OS), biochemical relapse-free survival (BRFS) and distant metastases-free survival (DMFS) rates were 88%, 78%, and 79%, respectively. Higher RT doses (≥78 Gy) and longer ADT duration (≥2 years) were significant predictors for improved DMFS, whereas advanced stage was a negative prognosticator for DMFS in patients with GS 9-10. CONCLUSIONS: Our results validated the fact that oncologic outcomes after radical EBRT significantly differ in men with GS 8 versus those with GS 9-10 prostate cancer. We found that EBRT dose was important predictive factor regardless of ADT period. Patients receiving 'non-optimal treatment' (RT doses <78 Gy and ADT period <2 years) had the worst treatment outcomes.

Lymphopaenia and accidental splenic doses: Do they have any prognostic value for locally advanced gastric cancer patients treated with radiochemotherapy?

AIM OF THE STUDY: To determine the effect of chemoradiotherapy (CRT)-induced lymphopaenia, and irradiated splenic volume and splenic doses on oncological outcomes in patients with locally advanced gastric cancer (LAGC). MATERIAL AND METHODS: A consecutive cohort of 52 patients with LAGC treated between 2005 and December 2016 was included. The absolute neutrophil, lymphocyte, and platelet counts were recorded prior to any treatment (baseline), just after the completion of CRT, and 2 -6 weeks after the completion of CRT (control evaluation). RESULTS: The median follow-up time was 30 months (range, 8 -130). The incidence of severe lymphopaenia was only 1% at control evaluation, but it was 93% after CRT (p< 0.001). Both in univariate and multivariate analyses, stage 3 disease (p< 0.001 and p = 0.041, respectively) and metastatic to dissected lymph node (MDLN) ratio > 20% (p< 0.001 and p = 0.032) had a negative effect on OS. Mean splenic dose ≥ 35 Gy was a significant poor prognostic factor for OS and recurrence-free survival (RFS) (p = 0.042 and p = 0.50, respectively). Maximum splenic dose ≥ 58 Gy effected OS unfavourably (p = 0.050). Volumetric modulated arc therapy (VMAT), intravenous CT, and age ≥ 65 years were significant predictors for subsequent severe lymphopaenia. CONCLUSIONS: Severe lymphopaenia could not be accepted as a predictive or prognostic factor for LAGC. Mean and maximum splenic doses should be kept on mind while evaluating the treatment dose-volume histograms (DVHs). Patient age, IV usage of concomitant CT agent, and RT technique can influence the ALC. Disease-related factors such as stage and MDLN ratio were the most important factors.

Does a patient-specific bladder-filling protocol affect bladder volume and dose in postprostatectomy radiotherapy?

PURPOSE: Our aim is to develop a patient-specific bladder-filling protocol (PSP) using an ultrasound-based bladder scanner (BS) and compare the volumetric and dosimetric parameters with those of the standard filling protocol (SP) in postprostatectomy patients. METHODS: Twenty postprostatectomy patients who received salvage radiotherapy (72 Gy/36 fx) were included. For PSP, the patient was asked to drink 500 mL of water after emptying his bladder. Bladder volume was measured using BS every 10 min. Each patient's unique time to reach a 150-200 cc volume was used for simulation and treatment. For the SP, the patient was asked about the feeling of having a full bladder. Organs at risk (OAR) were contoured on cone-beam computed tomography (CBCT) scans that were transferred to the treatment planning system (TPS). Treatment plans were applied to CBCTs. Changes in bladder volume and doses for planning computed tomography (PCT) and CBCT were determined. RESULTS: In the SP, there was no significant difference in mean bladder volume for PCT and CBCT (p = 0.139); however, there was a trend for significance in the mean bladder dose (p = 0.074). In PSP, there was no significant difference in the mean bladder volume or dose for PCT and CBCT (p = 0.139 and p = 0.799, respectively). There was a significant difference in terms of mean CBCT bladder volume between the two protocols (p = 0.007), whereas no significant difference was detected in terms of bladder dose (p = 0.130). CONCLUSION: With PSP, optimal bladder filling was obtained and maintained throughout the whole treatment course, and it was reproducible in every fraction.

HPV status and immunohistochemical analysis of p16, p53 and PD­L1 expression as prognostic biomarkers in patients with squamous cell anal cancer receiving definitive radiotherapy/chemoradiotherapy.

Anal squamous cell carcinoma (SCC) treated with definitive radiotherapy (RT)/chemoradiotherapy (CRT) has shown high success rates, yet challenges such as treatment resistance and recurrence persist. The present study aimed to investigate the associations between immunohistochemical (IHC) evaluation, treatment response and prognosis in anal SCC. A retrospective cohort analysis included 42 patients with anal SCC treated at a single institution between 2006 and 2022. Human papillomavirus (HPV) status was determined, and the IHC analysis of p16, p53 and PD-L1 expression was conducted using formalin-fixed, paraffin-embedded biopsies. A complete response to RT/CRT was observed in 71.4% of patients. Recurrence occurred in 38.1% of cases, of which 7.1% had local-regional recurrence (LRR), 14.3% had distant recurrence (DR), and 16.7% had both LRR and DR. HPV positivity (71.4%) was significantly associated with p16 positivity. Lack of complete response was associated with HPV-negative status, p16-negative status, increased recurrence and DR. In addition, recurrence was significantly associated with p53-positive status, and p53 positivity was significantly associated with increased LRR. PD-L1 positivity, defined as a combined positive score (CPS) ≥1% was found in 73.8% of the patients, and exhibited significant associations with HPV positivity and p16 positivity. PD-L1 CPS ≥ 1% was also associated with an increased LRR. Univariate analysis revealed that age <65 years, a complete response and HPV positivity were associated with increased 5-year overall survival (OS), while a complete response, HPV positivity and p53-negative status were associated with increased 5-year disease-free survival (DFS). Multivariate analysis identified that age <65 years and HPV positivity are independent prognostic factors for 5-year OS, and a complete response and p53-negative status are independent prognostic factors for 5-year DFS. In conclusion, these findings suggust that the identification of HPV status and poor prognostic biomarkers at diagnosis may be used to guide personalized treatment strategies, with the combination of immunotherapy with standard CRT potentially providing improved outcomes.

Evaluation of treatment outcomes and tolerability in older patients with rectal cancer treated with radiotherapy accompanied by the G-8 geriatric score: TROD13-003 multicenter study.

INTRODUCTION: The choice of treatment for rectal cancer often differs in older and younger patients, with the rate of radiotherapy use lower among older adults. In our daily practice, when evaluating a frail older patient with rectal cancer, we usually choose to give less treatment. This may be due to concern that the patient will not be able to tolerate radiotherapy. The Geriatric 8 score (G8GS) is a guide to evaluating treatment tolerability as it relates to frailty in older adults with cancer. The aim of this study was to evaluate treatment outcomes and tolerability in older patients with rectal cancer treated with radiotherapy (RT) accompanied by G8GS. MATERIALS AND METHODS: Patients aged 65 and older with stage I-III rectal adenocarcinoma who were treated with RT and had a G8 evaluation were included in this multicenter retrospective study. Prognostic factors related to G8GS were calculated using Chi-square and logistic regression tests and survival rates were calculated by the Kaplan-Meier test using the SPSS v24.0 software. All p-values ≤0.05 were considered statistically significant. RESULTS: A total of 699 patients from 16 national institutions were evaluated. The median age was 72 years (range 65-96), and the median follow-up was 43 (range 1-190) months. Four hundred and fifty patients (64%) were categorized as frail with G8GS ≤14 points. Frail patients had higher ages (p = 0.001) and more comorbidities (p = 0.001). Ability to receive concomitant and/or adjuvant chemotherapy rates were significantly higher in fit patients (p = 0.002 and p = 0.001, respectively). No significant difference was observed in terms of grade 3-4 early and late toxicity for both groups. Cancer-related death was higher (p = 0.003), and 5- and 8-year survival rates were significantly lower (p = 0.001), in the frail group. Age and being frail were significantly associated with survival. DISCUSSION: Radiotherapy is a tolerable and effective treatment option for older adults with rectal cancer even with low G8GS. Being in the frail group according to G8GS and having multiple comorbidities was negatively associated with survival. Addressing the medical needs of frail patients through a comprehensive geriatric assessment prior to radiotherapy may improve G8GS, allowing for standard treatment and increased survival rates.

Who would be the winner? A prognostic nomogram for predicting the benefit of postoperative radiotherapy ± chemotherapy in patients with locally advanced gastric cancer: TROD-02-01 study.

OBJECTIVES: We aimed to develop a basic, easily applicable nomogram to improve the survival prediction of the patients with stage II/III gastric cancer (GC) and to select the best candidate for postoperative radiotherapy (RT). METHODS: In this multicentric trial, we retrospectively evaluated the data of 1597 patients with stage II/III GC after curative gastrectomy followed by postoperative RT ± chemotherapy (CT). Patients were divided into a training set (n = 1307) and an external validation set (n = 290). Nomograms were created based on independent predictors identified by Cox regression analysis in the training set. The consistency index (C-index) and the calibration curve were used to evaluate the discriminative ability and accuracy of the nomogram. A nomogram was created based on the predictive model and the identified prognostic factors to predict 5-year cancer-specific survival (CSS) and progression-free survival (PFS). RESULTS: The multivariate Cox model recognized lymph node (LN) involvement status, lymphatic dissection (LD) width, and metastatic LN ratio as covariates associated with CSS. Depth of invasion, LN involvement status, LD width, metastatic LN ratio, and lymphovascular invasion were the factors associated with PFS. Calibration of the nomogram predicted both CSS and PFS corresponding closely with the actual results. In our validation set, discrimination was good (C-index, 0.76), and the predicted survival was within a 10% margin of ideal nomogram. CONCLUSIONS: In our relatively large cohort, we created and validated both CSS and PFS nomograms that could be useful for underdeveloped or developing countries rather than Korea and Japan, where the D2 gastrectomy is routinely performed. This could serve as a true map for oncologists who must make decisions without an experienced surgeon and a multidisciplinary tumor board.

Does neoadjuvant rectal score predict treatment outcomes better than the all grading systems used in neoadjuvantly treated rectal cancer?

BACKGROUND: /Objective: To compare the prognostic value of the yield pathologic (yp) stage, used 4 tumor regression grading (TRG) systems, and neoadjuvant rectal score(NARS) in patients with locally advanced rectal cancer (LARC) who received long-term neoadjuvant chemoradiotherapy (nCRT). METHODS: Between 2005 and 2017, we included 302 patients with LARC who treated with nCRT. Postoperative pathological responses were graded by using Dworak, American Joint Committee on Cancer, Mandart, Memorial Sloan Kettering Cancer Center, grading systems and NARS([5ypN-3(kT-pT)+12]2/9,61) calculations. Their results were compared in terms of treatment outcomes. RESULTS: The median follow-up time was 51 months (range 5-136). There was a significant relation between cT stage and the response in used grading systems(p < 0,001). Median overall(OS), local recurrence free(LRFS), and distant metastasis free(MFS) survival rates were 50, 48, and 45 months, respectively. 5-year OS, LRFS, and MFS rates were 71%, 92%, and 72%, respectively. According to the NARS and treatment response grating systems, a significant difference was found between the low risk and high risk groups in terms of OS, LRFS, and MFS rates. While it was not seen any difference in terms of OS and MFS, NARS was found to predict LRFS better than other grading systems. In multivariate analysis, high NARS was found to be correlated with worse OS and worse MFS. On the other hand, pCR was the another important factor affecting treatment outcomes. CONCLUSIONS: While used systems except NARS group patients according to ypT status in surgical tissue, NARS add the value of ypN status in addition to ypT status. It could be suggested to use NARS to predict LRFS.

Evaluation of the relationship between the eighth edition of TNM staging, the mMasoaka, and World Health Organization histopathological classification for thymoma.

Aim of Study: The aim of this study was to describe the correlation between the eighth tumor, node, and metastasis (TNM), mMasaoka staging, and the World Health Organization (WHO) histopathologic classification and to identify prognostic values in predicting survival and recurrence of thymoma. Materials and Methods: Medical files of 90 patients with thymoma diagnosed between 1992 and 2018 were evaluated for this trial. Results: The distributions of patients were similar between mMasaoka and eighth TNM staging according to early (I, II) and advanced stages (IIIA, IIIB, IV). Interestingly, 55 of 63 stage I patients with TNM staging showed difference as 31 of them up-staged to stage IIA and 24 of them up-staged to stage IIB in mMasoaka staging. Both staging systems closely correlated with WHO classification (p < 0.001); stages I and II were associated with low-risk groups (type A, AB, B1), and stages III and IV were associated with high-risk groups (type B2, B3). WHO classification was not a prognostic factor for overall survival (OS) (P = 0.13) and progression-free survival (PFS) (p = 0.08), but it was a prognostic factor for 10-year cancer-specific survival (CSS) (p = 0.04). Myasthenia gravis was associated to early stages (stage I, II) (p = 0.007) and related with better prognosis. Conclusions: Our study showed a correlation between both staging system and WHO classification. A certain difference was found between eighth TNM staging and the mMasoaka staging in terms of stage I disease. Both staging systems effectively prognosticated OS, CSS, and PFS. To clarify the prognostic relevance and clinical usefulness of the WHO classification may be beneficial in clinical practice for the treatment decision.

Postoperative radiotherapy in rectal cancer: long-term results of 290 patients.

BACKGROUND/AIMS: To evaluate treatment results and to identify prognostic factors affecting local-relapse-free (LRFS), disease-free (DFS) and overall survival (OS) in patients treated with postoperative radiotherapy (RT) for rectal cancer. METHODOLOGY: A retrospective review was performed in 290 patients treated between January 1990 and December 2005. Median RT dose was 54 Gy. A total of 220 (75.8%) patients also received 5-fluorouracil based chemotherapy. RESULTS: During a median follow-up of 56 months (range 9-216 months), 68 patients (23.4%) developed local recurrence and 96 patients (33.1%) developed distant metastases. Five-year LRFS, DFS, and OS rates were 74.6%, 52.6%, and 53.7%, respectively. On multivariate analysis, significant prognostic factors for LRFS were age, pathologic T stage (pT), and distance from anal verge; for DFS were pT stage, and positive surgical margin; for OS were pT and pathologic N (pN) stages. One hundred and fifty-two node-positive patients whose number of retrieved and metastatic nodes are known were evaluated according to the lymph node ratio (LNR). OS and DFS rates significantly decreased with increasing LNR (p = 0.005, and p = 0.023 respectively). RT related Grade 3-4 late morbidity rate was 3.1%. A second primary malignancy developed in 4.8% of patients. CONCLUSION: Among several prognostic factors, pT stage significantly predicted for LRFS, DFS and OS on multivariate analysis, while pN stage was significant for all three only on univariate analysis. LNR which affected DFS and OS could be an important tool for prognostic prediction for node-positive patients.

Postoperative gemcitabine alone and concurrent with radiation therapy in locally advanced pancreatic carcinoma.

AIMS AND BACKGROUND: To evaluate the treatment results of gemcitabine alone and concurrent with radiotherapy after R0/R1 resection of locally advanced pancreatic cancer. METHODS AND STUDY DESIGN: From 1999 to 2005, 55 patients with stage II resected pancreatic cancer treated with gemcitabine-based radiochemotherapy were retrospectively evaluated. Initially, one cycle of induction gemcitabine was administered and followed by weekly gemcitabine concurrent with radiotherapy. After the completion of radiochemotherapy, patients received 3 additional courses of gemcitabine. RESULTS: Thirteen patients were stage IIA and 42 were stage IIB. Forty-six patients (83.6%) had R0 and 9 patients (16.4%) had R1 resection. All of the patients received induction chemotherapy and radiotherapy, all but 3 received concurrent radiochemotherapy, and 46 (84%) patients received maintenance chemotherapy. During induction, concurrent and maintenance phases of the protocol, 11%, 13.5% and 19.5% of the patients had at least one > or = grade 3 toxicity, respectively. Within a median 47 months (range, 34-105) of follow-up, 4 (7.3%) patients had isolated local recurrence, 5 (9%) patients had local recurrence and distant metastases, and 27 (49%) had only distant metastases. Median disease-free survival and overall survival were 13 (range, 4-105) and 19 months (range, 6-105), respectively. In multivariate analysis, nodal stage, AJCC stage and number of lymph nodes dissected were the significant factors affecting disease-free survival whereas Karnofsky performance status was the only significant factor for overall survival. CONCLUSIONS: The prognosis for pancreatic cancer remains poor despite adjuvant radiochemotherapy. More aggressive treatments should be considered in patients with unfavorable prognostic factors.

Prognostic significance of early complete response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy: Multicentric study of Turkish Society for Radiation Oncology Group (TROD).

BACKGROUND/AIMS: To assess the effect of various parameters on the oncologic outcomes, including the time interval between therapy and surgery (S) in locally advanced rectal cancer (LARC) patients receiving preoperative chemoradiotherapy (CRT). MATERIALS AND METHODS: The data of 914 LARC patients who received preoperative CRT between 1994 and 2015 were collected retrospectively. Patients received 45-50.4 Gy RT with 5FU based chemotherapy (CT). They all underwent radical resection followed by maintenance CT. Clinical and pathologic variables were compared between the pCR and no-pCR groups. Survival was estimated by the Kaplan-Meier method and Cox proportional hazard model was used in multivariate analysis. RESULTS: After median follow-up of 60.5 (range=12-297.6) months, median overall survival (OS) was 58.75 months and disease-free survival (DFS) 53.32 months. pCR was observed in 18.9% of all cases. pCR, lymphovascular invasion and metastatic lymph node ratio (mLNR) were significantly associated with OS and DFS on multivariate analysis. The 5-year OS and DFS rates were better in pCR group (95.3% vs 80.7% for OS, p<0.0001 and 87.4% vs 71% for DFS, p<0.0001). pCR patients with 4-8 weeks interval had lower rates of distant metastasis (9% vs 20%, p=0.01) and any recurrences (13.6% vs 29.6%, p=0.001) than the remaining. Both OS and DFS were better in favor of pCR achieved at 4-8 week interval time (p<0.0001 for each). CONCLUSION: pCR after preoperative CRT in LARC correlated with better oncologic outcome. The best OS and DFS durations were achieved in patients who experienced pCR after 4-8-weeks interval before surgery.

Atypical and malignant meningioma: outcome and prognostic factors in 119 irradiated patients. A multicenter, retrospective study of the Rare Cancer Network.

PURPOSE: To retrospectively analyze and assess the outcomes and prognostic factors in a large number of patients with atypical and malignant meningiomas. METHODS AND MATERIALS: Ten academic medical centers participating in this Rare Cancer Network contributed 119 cases of patients with atypical or malignant meningiomas treated with external beam radiotherapy (EBRT) after surgery or for recurrence. Eligibility criteria were histologically proven atypical or anaplastic (malignant) meningioma (World Health Organization Grade 2 and 3) treated with fractionated EBRT after initial resection or for recurrence, and age >18 years. Sex ratio (male/female) was 1.3, and mean (+/-SD) age was 57.6 +/- 12 years. Surgery was macroscopically complete (Simpson Grades 1-3) in 71% of patients; histology was atypical and malignant in 69% and 31%, respectively. Mean dose of EBRT was 54.6 +/- 5.1 Gy (range, 40-66 Gy). Median follow-up was 4.1 years. RESULTS: The 5- and 10-year actuarial overall survival rates were 65% and 51%, respectively, and were significantly influenced by age >60 years (p = 0.005), Karnofsky performance status (KPS) (p = 0.01), and high mitotic rate (p = 0.047) on univariate analysis. On multivariate analysis age >60 years (p = 0.001) and high mitotic rate (p = 0.02) remained significant adverse prognostic factors. The 5- and 10-year disease-free survival rates were 58% and 48%, respectively, and were significantly influenced by KPS (p = 0.04) and high mitotic rate (p = 0.003) on univariate analysis. On multivariate analysis only high mitotic rate (p = 0.003) remained a significant prognostic factor. CONCLUSIONS: In this multicenter retrospective study, age, KPS, and mitotic rate influenced outcome. Multicenter prospective studies are necessary to clarify the management and prognostic factors of such a rare disease.

High dose rate endobronchial brachytherapy in the management of lung cancer: response and toxicity evaluation in 158 patients.

The aim of this study was to evaluate the symptomatic and endoscopic responses as well as the toxicities in 158 patients with endobronchial lung cancer treated with high dose rate endobronchial brachytherapy (HDR-EB). Forty-three patients with stage III NSCLC were treated with 60Gy external beam radiotherapy (ERT) and three applications of 5Gy each of HDR-EB (group A). Seventy-four patients who did not receive previous RT were treated with 30Gy ERT and two applications of 7.5Gy HDR-EB with palliative intent (group B). Forty-one patients with recurrent tumor who were irradiated previously were treated with three applications of 7.5Gy HDR-EB, with palliative intent (group C). In group A, bronchoscopic complete (CR) and overall response rates (ORR) were 67% and 86%, respectively. Symptomatic improvement was obtained in 58% of patients with cough, 77% of patients with dyspnea and 100% of patients with hemoptysis. Two and 5-year survival rates were 25.5% and 9.5%, respectively and the median survival time (MST) was 11 months. In group B, the bronchoscopic CR and ORR were 39% and 77%, respectively and 28% and 72% in group C. The symptomatic response rates were 57% and 55% for cough, 90% and 78% for dyspnea and 94% and 77% for hemoptysis, with a MST of 7 and 6 months in Groups B and C, respectively. Eighteen patients (11%) died of fatal hemoptysis (FH) with the median time to this event of 7 months. Treatment intent (p<0.001), total BED (p<0.001) and the number of HDR-EB fractions (p<0.001) were significant prognostic factors for FH. HDR-EB provides effective palliation in relieving the symptoms of patients with endobronchial lung cancer, however, there is a risk of developing FH that is associated with a high BED and multiple HDR-EB applications.

Mature results of neoadjuvant chemotherapy followed by radiotherapy in nasopharyngeal cancer: is it really old fashioned?

Nasopharyngeal carcinoma (NPC) is known as a radiosensitive and chemosensitive tumor. The interest in neoadjuvant chemotherapy (NACT) has been refreshed in recent years due to promising results with more effective chemotherapeutic agents in head and neck tumors. The aim of this retrospective study is to evaluate the long-term toxicity and efficacy of NACT followed by radiotherapy (RT). From January 1995 to December 2002, 73 NPC patients were consecutively treated at Ege University Medical School Department of Radiation Oncology and the results were analyzed retrospectively. The NACT consisted of cisplatin 100 mg/m(2)/day and epirubicine 100 mg/m(2)/day, every 3 weeks. External radiotherapy by conventional fractionation was delivered 3 weeks after NACT. Response evaluated after NACT followed by radiotherapy showed 75% complete response (CR) rate. After a median follow-up time of 74 months, 32 relapses were noted. Most of the local failures were observed in 2 years (median 17 months) and the most common site for distant failure was bone. A total of 27 deaths had occurred due to uncontrolled disease. Xerostomia, soft tissue fibrosis and loss of sensorineural hearing were the most common long-term side effects. Only one treatment related death was observed and this patient died due to temporal lobe necrosis 22 months after the radiotherapy. The 5-year disease-free, distant metastasis-free and overall survival rates were 58, 77 and 68%, respectively. Current study showed that NACT with cisplatin and epirubicine followed by radiotherapy provided promising results with low toxicity in NPC patients.

Resources and management strategies for the use of radiotherapy in the treatment of lung cancer in Central and Eastern European countries: results of an International Atomic Energy Agency (IAEA) survey.

PURPOSE: To assess resources and management strategies for the use of radiotherapy (RT) in the treatment of lung cancer in developing Central and Eastern European countries. MATERIALS/METHODS: Questionnaires on patterns of care of NSCLC and SCLC were sent to radiation oncologists of Central and Eastern Europe. Comparisons were made between two groups of countries-ex-USSR states and other Eastern and Central European countries. RESULTS: Twenty-four out of twenty-eight surveyed countries responded. There were significant differences in access to modern treatment facilities (3D planning systems, number of linear accelerators), percentage of patients with lung cancer receiving radiotherapy, schedules of palliative RT, use of postoperative RT for early stages between both analysed groups of countries. 3D systems were in use in 25% of centres for an entire treatment, in 28% for a part of the treatment, and in 47% curative RT was 2D planned. Sequential chemo-RT was the most common approach to radical management of NSCLC, followed by RT alone and concomitant chemo-RT; median percentages of patients receiving respective treatments per centre were 57%, 30%, and 10%. For SCLC, the concurrent approach was declared by 56%, and the sequential approach by 42% of responders. CONCLUSIONS: Patterns of care of lung cancer in the analysed countries differed in some part from existing, evidence-based data on lung cancer. In particular, this difference was observed between ex-USSR countries and the rest of European developing countries in the equipment available and specific diagnostic and treatment parameters in radiotherapy of lung cancer, the latter group's practices more resembling those of developed European countries.

Evaluation of the Radiation Dose-Volume Effects of Optic Nerves and Chiasm by Psychophysical, Electrophysiologic Tests, and Optical Coherence Tomography in Nasopharyngeal Carcinoma.

PURPOSE: To evaluate the radiation dose-volume effects of optic nerves and chiasm by visual psychophysical, electrophysiologic tests, and optical coherence tomography in patients with locally advanced nasopharyngeal carcinoma. MATERIALS AND METHODS: A series of visual tests including visual acuity, visual field, contrast sensitivity, visual evoked potential, and optical coherence tomography were administered to 20 patients with locally advanced (T3-T4) nasopharyngeal carcinoma who were treated with definitive chemoradiotherapy. Volume that received 55 Gy (V55), mean dose (Dmean), highest dose to 5% of the volume (D5), and maximum dose (Dmax) for optic nerves and chiasm were evaluated for each patient. Cutoff values were identified as V55: 50%, Dmean: 50 Gy, D5: 55 Gy, and Dmax: 60 Gy. The effects of radiation dose-volume on ophthalmologic tests were evaluated. RESULTS: Ophthalmological evaluation revealed optic neuropathy with simultaneous retinopathy in 6 eyes of 4 patients and radiation retinopathy alone in both eyes of 1 patient. Regarding radiation dose-volume effects of the optic nerve, significant detrimental effect of all parameters was observed on visual acuity. Visual field and contrast sensitivity were affected significantly with V55 ≥ 50% and Dmean ≥ 50 Gy. Visual evoked potential latency was affected significantly with Dmean ≥ 50 Gy, D5 ≥ 55 Gy, and Dmax ≥ 60 Gy. For the chiasm, significant detrimental effect of all parameters was observed on visual acuity as well. Retinal nerve fiber layer thickness and visual evoked potential amplitude were not affected by any of the dose-volume parameters neither optic nerves nor chiasm. CONCLUSION: The volume receiving the threshold dose, mean dose, and 5% of the volume receiving the maximum dose are important parameters besides maximum dose to optic nerves and chiasm. A comprehensive ophthalmological evaluation including visual field, contrast sensitivity, visual evoked potential latency, and amplitude should be performed for these patients. Visual evoked potential latency is an objective predictor of vision loss before the onset of clinical signs.

Neoadjuvant radiotherapy/chemoradiotherapy in locally advanced non-small cell lung cancer.

Locally advanced non-small cell lung cancer (NSCLC) consists of a heterogeneous group of patients, and the optimal treatment is still controversial. The current standard of care is concurrent chemoradiotherapy. The prognosis is still poor, with high rates of local and distant failure despite multimodality treatment. One of the efforts to improve outcomes in these patients is to use neoadjuvant treatment to improve resectability, and downstaging the nodal disease, which has a clear impact on prognosis. Radiotherapy as the sole neoadjuvant modality has been used historically without any survival benefit, but with increased toxicity. After the demonstrating a survival benefit by combining radiotherapy and chemotherapy, phase II studies were started to determine the neoadjuvant administration of these two modalities together. Although the results of these studies revealed a heterogeneous postinduction pathologic complete response, tumor and nodal down-staging can be achieved at the cost of a slightly higher morbidity and mortality. Subsequent phase III trials also failed to show a survival benefit to surgery, but indicated that there may be a subset of patients with locally advanced disease who can benefit from resection unless pneumonectomy is not provided. In order to increase the efficacy of radiotherapy, hyperfractionated-accelerated schedules have been used with promising complete pathologic response rates, which might improve prognosis. Recently, studies applying high radiotherapy doses in the neoadjuvant setting demonstrated the safety of resection after radiotherapy, with high nodal clearance rates and encouraging long-term survival results. In conclusion, neoadjuvant treatment of locally advanced NSCLC is one of the most challenging issues in the treatment of this disease, but it can be offered to appropriately selected patients, and should be done by a multidisciplinary team. Individual risk profiles, definite role of radiotherapy with optimal timing, and dose need to be clarified by carefully designed clinical trials.

Can adaptive threshold-based metabolic tumor volume (MTV) and lean body mass corrected standard uptake value (SUL) predict prognosis in head and neck cancer patients treated with definitive radiotherapy/chemoradiotherapy?

PURPOSE: To evaluate the predictive value of adaptive threshold-based metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax) and maximum lean body mass corrected SUV (SULmax) measured on pretreatment positron emission tomography and computed tomography (PET/CT) imaging in head and neck cancer patients treated with definitive radiotherapy/chemoradiotherapy. MATERIALS AND METHODS: Pretreatment PET/CT of the 62 patients with locally advanced head and neck cancer who were treated consecutively between May 2010 and February 2013 were reviewed retrospectively. The maximum FDG uptake of the primary tumor was defined according to SUVmax and SULmax. Multiple threshold levels between 60% and 10% of the SUVmax and SULmax were tested with intervals of 5% to 10% in order to define the most suitable threshold value for the metabolic activity of each patient's tumor (adaptive threshold). MTV was calculated according to this value. We evaluated the relationship of mean values of MTV, SUVmax and SULmax with treatment response, local recurrence, distant metastasis and disease-related death. Receiver-operating characteristic (ROC) curve analysis was done to obtain optimal predictive cut-off values for MTV and SULmax which were found to have a predictive value. Local recurrence-free (LRFS), disease-free (DFS) and overall survival (OS) were examined according to these cut-offs. RESULTS: Forty six patients had complete response, 15 had partial response, and 1 had stable disease 6 weeks after the completion of treatment. Median follow-up of the entire cohort was 18 months. Of 46 complete responders 10 had local recurrence, and of 16 partial or no responders 10 had local progression. Eighteen patients died. Adaptive threshold-based MTV had significant predictive value for treatment response (p=0.011), local recurrence/progression (p=0.050), and disease-related death (p=0.024). SULmax had a predictive value for local recurrence/progression (p=0.030). ROC curves analysis revealed a cut-off value of 14.00 mL for MTV and 10.15 for SULmax. Three-year LRFS and DFS rates were significantly lower in patients with MTV ≥ 14.00 mL (p=0.026, p=0.018 respectively), and SULmax≥10.15 (p=0.017, p=0.022 respectively). SULmax did not have a significant predictive value for OS whereas MTV had (p=0.025). CONCLUSION: Adaptive threshold-based MTV and SULmax could have a role in predicting local control and survival in head and neck cancer patients.