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Perpetual advances in the diagnostic tools, local plus systemic cancer treatments, and ensued lengthened survival times led to striking increments in the incidence rates of brain metastases (BMs), with a collective incidence range of 20-40% for all solid cancers. Stereotactic radiosurgery (SRS) and innovative molecularly targeted therapies are continuously gaining growing significance in the triumphant management of BMs, as the brain represents a sanctuary site for the vast majority of the conventional cytotoxic chemotherapies. In this scenario, the molecularly targeted agents appear to be an attractive alternative to traditional chemotherapeutics as they can modulate cancer metabolism and progression and exert synergism with radiation therapy. Therefore, the present paper intends to sum up the accessible proof on the consolidated utilization of SRS and molecularly targeted agents in the precise management of BMs from certain solid cancers, specifically the non-small-cell lung, breast, and renal-cell carcinomas, and malignant melanomas.

Stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) have settled down in the center of modern palliative and recently curative intent treatments in the last two decades. Being special, technology-driven, direct knowledge and experience based clinical procedures, both SRS and SBRT require high precision, accuracy and reproducibility to be safely and effectively delivered, which delineates the importance of quality assurance (QA) procedures from head to toe. In this review, we focused on summary of the comprehensive QA program covering clinical, technical and patient-specific treatment aspects, which need to be individualized per department based on several current recommendation guidelines.

Stereotactic radiosurgery (SRS) has been utilized broadly for brain metastases not only for intact ones but as well as of late for the postoperative cavity of metastases after surgery, due to the advantages of SRS to preserve neurocognitive functions, maintain local control and prescribe the treatment in a short time frame. Randomized trials have proven the safety and efficacy of cavity SRS compared to observation. As WBRT offers no survival advantage in comparison to SRS and frequent monitorization with brain MRIs for early salvage upon failure, there has been a revolution in clinical approach for patients with limited intact brain metastases to treat with SRS only and omit WBRT. Likewise, the postoperative cavity SRS for brain metastases has gained a growing reputation. In this review, we summarize the proof for evidence-based optimization in the postoperative setting of the surgically removed brain metastases.

As a notable cause of cancer-related morbidity and mortality, brain metastases (BMs) represent the most prevalent intracranial tumors arising in up to 40% of all adult solid tumors during the course of treatment. Intracranial stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) gained wide appreciation by the radiation oncology communities for the treatment of BM with regards to the grim prognosis of such patients after alternative therapies, including the whole brain radiotherapy (WBRT). Additional concerns on the neurocognitive deterioration and comparably low tumor control rates offered by the conventional WBRT further quickened the implementation of SRS to the daily practice of radiation oncology clinics. However, the striking diversities among the treatment algorithms and the treatment planning systems of the gamma knife-, linear accelerator- (LINAC), tomotherapy-, robotic Cyberknife-, or the proton therapy-based SRS render the administration of SRS/FSRT challenging. Acknowledging these difficulties, the present review intended to offer a thorough outline of the main principals of the SRS/FSRT technique from the initial patient fixation to the final machine and dose delivery quality assurance treads.

Brain metastases (BMs), the most frequent intracranial tumors, are diagnosed in approximately 30% of all adult patients over the span of planned treatment against a broad spectrum of solid cancers. The prognosis of patients presenting with BM is bleak with an expected median OS of only 4-7 months. However, some particular patients’ groups may enjoy longer survival durations with effective systemic and local therapies. At present, the feasible alternatives for active management of BMs typically include the whole-brain radiotherapy (WBRT), surgery, definitive SRS, postoperative SRS, systemic chemotherapy, targeted therapies, and their combination variants. Considering the local treatment, the severe neurotoxic effects of WBRT, and the increased risk for radionecrosis and leptomeningeal dissemination after postoperative SRS and together with the ineligibility of certain patients during the postoperative period prompted the energetic quest of alternative treatment strategies for such patients. In this respect, the novel preoperative SRS (PO-SRS) was proposed to provide at least equivalent local control rates with lesser radionecrosis and leptomeningeal dissemination risk. Respecting the scarcity of related literature, the present review aimed to meticulously detail theplausible rationale and accessible evidence for the novel PO-SRS in the management of patients presenting with BMs.

Brain metastases (BM) of various primaries merely remain the most prevalent type of intracranial tumors, and approximately 25% of all cancer patients are diagnosed with this poor prognostic disease condition somewhere during their treatment course. Contingent upon the general wellbeing status of the potential patient, currently available major treatment options typically include palliative radiotherapy, chemotherapy, and best supportive care. Various published studies have convincingly shown the likelihood to stratify BM patients into particular prognostic gatherings according to the conceivable combinations of multiple patients- and tumor-related characteristics; namely the prognostic scoring systems, which might be useful in the accurate prediction of survival, and thusly, the appropriate choice of the best-fit treatment alternative. In this present article, we meant to review the pros and cons of the as of now accessible and broadly acknowledged prognostic scoring systems for BMs and their clinical values.

Brain metastases (BMs) represent the most common intracranial tumors, and nearly 25% of all cancer patients are diagnosed with this poor prognostic disease condition somewhere during their treatment course. Depending on the potential patient's general well-being status, the main prevailing treatment options typically incorporate palliative radiotherapy, chemotherapy, targeted agents, immunotherapy, best supportive care, and less frequently surgery in select patients. Past investigations demonstrated the probability to stratify BM patients into particular prognostic gatherings according to the credible combinations of multiple patients- and tumor-related features: the prognostic scoring systems. Such frameworks may serve usefully in the accurate prediction of survival outcomes and the appropriate selection of the best-fit treatment elective. In this present review, we intended to survey the advantages and disadvantages of the broadly recognized on-the-spot prognostic scoring systems for BMs and their clinical merits.

To investigate the prognostic significance of pre-treatment Glasgow prognostic score (GPS) in stage IIIB non-small-cell lung cancer (NSCLC) older patients treated with radical concurrent chemoradiotherapy (C-CRT).We included 83 stage IIIB NSCLC older patients (age 70 years) treated with C-CRT consisting of 60-66 Gy (2 Gy/fx) thoracic radiotherapy and at least 1 cycle of platinum-based chemotherapy. Patients were grouped into three: GPS-0: c-reactive protein (CRP) ≤ 10 mg/L and albumin35 g/L, GPS-1: CRP ≤ 10 mg/L and albumin ≤35 g/L or CRP 10 mg/L and albumin35 g/L, GPS-2: CRP 10 mg/L and albumin ≤35 g/L according to the definition. The relationship between GPS groups and overall survival (OS) was the primary objective, while locoregional- (LRPFS) and progression-free survival (PFS) were secondary objectives.For the whole cohort, the median OS, LRPFS, and OS were 19.7 (95% confidence interval [CI]: 16.8-22.6), 13.2 (95% CI: 8.7-17.7), and 8.3 months (95% CI: 6.6-10.0), respectively. Comparisons between the GPS-0, GPS-1, and GPS -2 groups revealed that the lower GPS was associated with significantly superior median OS (25.8 versus 16.3 versus 9.4 months; p .001) which retained its independent significance in multivariate analysis (p .001), as well. Similarly, the respective median LRPFS (20.0 versus 10.4 versus 6.3 months; p .001), and PFS (11.3 versus 7.3 versus 4.1 months; p .001) durations were also significantly longer in the earlier GPS groups.The present results suggested that the GPS was useful in three layered stratification of older stage IIIB NSCLC patients undergoing C-CRT in terms of OS, LRPS, and PFS times.

Representing the most common intracranial tumors brain metastases (BMs) are diagnosed in nearly 30% to 54% of all patients during or after their treatment courses against solid cancers. Although the prognosis of BM patients is extremely poor with an estimated median OS of usually less than 7 months. Nevertheless, nowadays some patients’ groups may experience significantly longer survival durations after the implementation of effective systemic and local therapies, such as surgery and radiotherapy (RT). Currently, the noteworthy alternatives for the management of BMs include the neurosurgery, whole-brain RT (WBRT), definitive SRS, postoperative SRS, systemic chemotherapy, targeted therapies, immunotherapy and their various blends. Regarding the local treatment maneuvers, the well-recognized severe neurotoxicity of WBRT and the augmented risk for radionecrosis and leptomeningeal dissemination after postoperative SRS and the ineligibility of certain patients during the postoperative period mandated the search for safer and potentially more effective treatment alternatives for such patients’ group. In this regard, the novel preoperative SRS (PO-SRS) was proposed to provide at least comparable local control rates with lesser radionecrosis and leptomeningeal dissemination risk. The present chapter details the conceivable rationale and available proof for the novel PO-SRS in the management armamentarium of the cancer patients presenting with BMs.

Stereotactic radiosurgery (SRS) has been utilized broadly for brain metastases not only for intact ones but as well as of late for the postoperative cavity of metastases after surgery, due to the advantages of SRS to preserve neurocognitive functions, maintain local control and prescribe the treatment in a short time frame. Randomized trials have proven the safety and efficacy of cavity SRS compared to observation. As WBRT offers no survival advantage in comparison to SRS and frequent monitorization with brain MRIs for early salvage upon failure, there has been a revolution in clinical approach for patients with limited intact brain metastases to treat with SRS only and omit WBRT. The recent implementation of the PO-SRS applications to the treatment algorithm of resected BMs has reputably enhanced the local control at the surgical resection bed in comparison to observation or WBRT Likewise, the postoperative cavity SRS for brain metastases has gained a growing reputation. In this review, we summarize the proof for evidence-based optimization in the postoperative setting of the surgically removed brain metastases.

Background: this preliminary simulation study aimed to compare the dosimetric outcomes of carotid arteries (CAs) and pharyngeal constrictor muscle (PCM) in patients with T1N0M0 glottic carcinoma undergoing helical tomotherapy-intensity modulated radiotherapy (HT-IMRT) and 3-dimensional conformal radiotherapy (3D-CRT) plans. Methods: in addition to the clinical target volume (CTV) which was defined as the entire larynx, the CAs and PCM of 11 glottic carcinoma patients were delineated. The CTV was uniformly expanded 5 mm to create a planning target volume (PTV) relative to the PCM and at a distance of 2 mm from the CA. The dosimetric characteristics in HT-IMRT and lateral opposed fields-based 3D-CRT plans were analyzed. Results: median D(95%)and V(100%)of PTV were significantly higher in HT-IMRT (p < 0.001) compared to 3D-CRT. The right/left CA dosimetric outcomes, including the mean doses (20.7/21.5 Gy versus 48.7/50.5 Gy), D-max(53.6/52.0 Gy versus 67.4/67.7 Gy), V-30(25.0/27.1% versus 77.6/80.3%), V-40(8.0/7.9% versus 74.6/71.9%), and V-50(2.0/1.2% versus 70.0/71.6%) were also significantly lower in HT-IMRT (p < 0.05), similar to the mean PCM doses (49.6 Gy versus 62.6 Gy for 3D-CRT;p < 0.001), respectively. Conclusions: our present results demonstrated the feasibility of simultaneous sparing of the CAs and PCM in HT-IMRT- compared to 3D-CRT plans in glottic carcinoma patients undergoing definitive radiotherapy., NA

Objectives. To evaluate the potential prognostic utility of pretreatment systemic immune-inflammation index (SII) in newly diagnosed glioblastoma multiforme (GBM) patients who underwent postneurosurgical radiotherapy and concurrent plus adjuvant temozolomide. Methods. The retrospective data of GBM patients who underwent postneurosurgical radiotherapy and concurrent plus adjuvant temozolomide were analyzed. For each patient, SII was calculated using the platelet, neutrophil, and lymphocyte measures obtained on the first day of treatment: SII=platelets×neutrophils/lymphocytes. The receiver operating characteristic (ROC) curve analysis was utilized for the evaluation of optimal cut-off values for SII those linked with the outcomes. Primary and secondary endpoints constituted the overall (OS) and progression-free survival (PFS) per conveyance SII group. Results. A total of 167 patients were included. The ROC curve analysis identified the optimum SII cut-off at a rounded 565 value that significantly interacted with the PFS and OS and stratified patients into two groups: low-SII (SII<565; n=71) and high-SII (SII≥565; n=96), respectively. Comparative survival analyses exhibited that the high-SII cohort had significantly shorter median PFS (6.0 versus 16.6 months; P<0.001) and OS (11.1 versus 22.9 months; P<0.001) than the low-SII cohort. The relationship between the high-SII and poorer PFS (P<0.001) and OS (P<0.001) further retained its independent significance in multivariate analysis, as well. Conclusions. The outcomes displayed here qualified the pretreatment SII as a novel independent prognostic index for predicting survival outcomes of newly diagnosed GBM patients undergoing postneurosurgical radiotherapy and concurrent plus adjuvant temozolomide.

Objective. We investigated the prognostic impact of C-reactive protein to albumin ratio (CRP/Alb) on the survival outcomes of newly diagnosed glioblastoma multiforme (GBM) patients treated with radiotherapy (RT) and concurrent plus adjuvant temozolomide (TMZ). Methods. The pretreatment CRP and Alb records of GBM patients who underwent RT and concurrent plus adjuvant TMZ were retrospectively analyzed. The CRP/Alb was calculated by dividing serum CRP level by serum Alb level obtained prior to RT. The availability of significant cutoff value for CRP/Alb that interacts with survival was assessed with the receiver-operating characteristic (ROC) curve analysis. The primary endpoint was the association between the CRP/Alb and the overall survival (OS). Results. A total of 153 patients were analyzed. At a median follow-up of 14.7 months, median and 5-year OS rates were 16.2 months (95% CI: 12.5–19.7) and 9.5%, respectively, for the entire cohort. The ROC curve analysis identified a significant cutoff value at 0.75 point (area under the curve: 74.9%; sensitivity: 70.9%; specificity: 67.7%; P<0.001) for CRP/Alb that interacts with OS and grouped the patients into two: CRP/Alb n = 61) and ≥0.75 (n = 92), respectively. Survival comparisons revealed that the CRP/Alb P<0.001) and 5-year (20% versus 0%) rates than the CRP/Alb ≥0.75, which retained its independent significance in multivariate analysis (P<0.001). Conclusion. Present results suggested the pretreatment CRP/Alb as a significant and independent inflammation-based index which can be utilized for further prognostic lamination of GBM patients.

Background: we retrospectively compared the incidence of isolated elective nodal failure (IENF) and toxicity rates and survival outcomes after elective nodal irradiation (ENI) versus involved-field RT (IFRT) by employing the propensity score matching (PSM) methodology in stage IIIB/C inoperable non-small-cell lung cancer (NSCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT). Methods: our PSM examination included 1048 stage IIIB/C NSCLC patients treated with C-CRT from January 2007 to December 2016: a total dose of 66 Gy (2 Gy/fraction) radiotherapy and 1-3 cycles of platinum-based doublet chemotherapy concurrently. The primary and secondary endpoints were the IENF and toxicity rates and survival outcomes after ENI versus IFRT, respectively. Propensity scores were calculated for each group to adjust for confounding variables and facilitate well-balanced comparability by creating 1: 1 matched study groups. Results: the median follow-up was 26.4 months for the whole study accomplice. The PSM analysis unveiled 1: 1 matched 646 patients for the ENI (N = 323) and IFRT (N = 323) cohorts. Intergroup comparisons discovered that the 5-year isolated ENF incidence rates (3.4% versus 4.3%; P=0.52) and median overall survival (25.2 versus 24.6 months; P=0.69), locoregional progression-free survival (15.3 versus 15.1 months; P=0.52), and progression-free survival (11.7 versus 11.2 months; P=0.57) durations were similar between the ENI and IFRT cohorts, separately. However, acute grade 3-4 leukopenia (P=0.0012), grade 3 nausea-vomiting (P=0.006), esophagitis (P=0.003), pneumonitis (P=0.002), late grade 3-4 esophageal toxicity (P=0.038), and the need for hospitalization (P, NA

We aimed to assess the efficacy of external beam radiotherapy (EBRT) in central airway obstruction (CAO) and associated factors for metastatic lung cancer (MLC) patients. Records of 72 MLC patients presenting with CAO were retrospectively analyzed. The serial chests X-rays prior and after the EBRT were compared for response assessment. The primary end-point was radiologic response, while overall-(OS) and CAO-free survival, and predictors of better outcomes constituted secondary endpoints. The EBRT doses ranged between 8 to 40 Gy (1-13 fractions). Median follow-up and OS were 5.6 (range: 1.3-17.8) and 7.6 months (95% CI: 6.5-8.7), respectively. Objective CAO resolution was achieved in 58 patients (80.6%) on serial chest X-rays with a median time to maximum CAO response of 23 days (range: 3-86). In responders the response was durable (8.1 months) almost nearly for all their remaining life spans (8.3 months) with only 19.0% CAO recurrences. Median OS was also significantly longer in responders (8.3 vs. 2.4 months; p= 39 Gy (p= 39 Gy (p=0.008) were the factors to relate with better OS on multivariate analyses. The EBRT proves effective and durable CAO palliation with only 19.0% re-CAO rate in MLC patients. Better CAO responses may be achieved in patients treated with smaller tumor size, small-cell histology, and higher BED10 values.

BACKGROUND: To compare the efficacies of standard dose-(SDRT) and escalated dose radiotherapy (EDRT) in newly diagnosed glioblastoma (GBM) with concurrent and adjuvant temozolomide (TMZ). MATERIALS AND METHODS: Outcomes of 126 newly diagnosed GBM patients who received SDRT (60 Gy, 30 fractions) or EDRT (70 Gy, 30 fractions) with concurrent plus adjuvant TMZ were retrospectively analyzed. Both groups received concurrent TMZ (75 mg/m2) during the course of RT and at least one course of adjuvant TMZ (150–200 mg/m2), thereafter. Overall survival (OS) and local progression free survival (LPFS) constituted the primary and secondary endpoints, respectively. RESULTS: At median 14.2 months follow-up, 26 (20.6%) patients were alive. Median LPFS and OS were 9.2 [95% confidence interval (CI); 8.4–10.0] and 15.4 months (95% CI; 12.1–18.8), respectively, for the entire cohort. Although the median OS was numerically superior in the EDRT this difference could not reach statistical significance (22.0 vs. 14.9 months; P = 0.45), Likewise, LPFS was also (9.9 vs. 8.9 months; P = 0.89) not different between the two treatment groups. In multivariate analysis, better recursive partitioning analysis class (3–4 vs. 5; P = 0.044) and extensive surgery (gross total resection vs. subtotal resection/biopsy only; P= 0.021) were identified to associate significantly with superior OS times, irrespective of the RT protocol. CONCLUSIONS: Although the current median OS of 22 months of the EDRT group is promising, no statistically significant survival advantage for EDRT was observed even in the presence of TMZ. Randomized studies with larger population sizes and available genetic markers are warranted to conclude more reliably on the fate of EDRT plus TMZ.

Purpose To assess the survival outcomes and prognostic factors of young (≤45 years) Stage IIIB nonsmall cell lung cancer (NSCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT). Materials and Methods Medical records of 145 Stage IIIB NSCLC patients (≤45 years) who received 60-66 Gy thoracic radiotherapy and concurrent 1-3 cycles of cisplatin-based doublet chemotherapy were retrospectively evaluated. The primary endpoint was overall survival (OS), while locoregional progression-free survival (LRPFS), progression-free survival (PFS), and evaluation of potential prognostic factors constituted the secondary endpoints. Results At median 21.6 months (range: 7.3-62.5) of follow-up, the median and 4-year survival estimates were 24.8 months and 24.2% for OS, 15.7 months and 18.9%, for LRPFS and 12.0 months and 11.2% for PFS, respectively. On univariate analyses, among all factors, the smaller tumor size (≤7.0 cm; P = 0.03), lower T-stage (T1-T2; P = 0.02), lower N-stage (N2; P = 0.01), absence of anemia before C-CRT (hemoglobin [Hb] ≥12 g/dL; P < 0.001), and lower/no pretreatment weight loss (WL ≤5%; P < 0.001) were found to be associated significantly with longer median OS durations, which also retained their independent significance on multivariate analyses, except for tumor size category. Conclusions The encouraging median 24.8 months OS duration observed here in young NSCLC patients accords well with the results of recent landmark locally advanced NSCLC series without age stratification. Other than the well-established T and N stages, extra exhibit of superior OS in patients with initial Hb ≥12 g/dL and ≤5% WL levels suggests a noteworthy prognostic role for these two latter variables in the stratification of such patients.

To investigate the incidence and influence of tumor cavitation (TC) on survival outcomes of locally advanced squamous cell lung cancer (LA-SqCLC) patients treated with concurrent chemoradiation therapy (C-CRT).Records of 789 stages IIIA/B squamous cell lung cancer (SqCLC) patients treated with C-CRT who received 1 to 3 cycles of platinum-based doublet chemotherapy during 60 to 66 Gy radiation therapy (RT) were analyzed retrospectively. Primary endpoint was the association between overall survival (OS) and pretreatment TC status. Secondary endpoints included locoregional progression-free survival (LRPFS), progression-free survival (PFS), and incidence of TC and correlated factors.Pretreatment TC occurred in 95 patients (12%), being significantly more common in those patients with ever-smoking history (12.6% vs 3.9%; P .001), weight loss5% (20.9% vs 7.1%; P .001), and hemoptysis (27.1% vs 6.4%; P .001). Rates of acute and late toxicities were similar in patients who presented with and without TC (P .05 for each). For the whole cohort, at a median follow-up of 22.9 months (range: 2.4-71.1), the respective median OS, LRPFS, and PFS estimates were 23.7, 14.7, and 10.7 months. In multivariate analysis, stage IIIB disease (P .001; hazard ratio [HR]: 1.33; 95% CI: 1.21-1.45), weight loss5% (P .001; HR: 2.10; 95% CI: 1.85-2.35), anemia (P .001; HR: 1.82; 95% CI: 1.67-1.97), and presence of TC (P .001; HR: 1.54; 95% CI: 1.37-1.71) appeared to be independently associated with poorer OS durations, likewise the LRPFS (P .001 for each of these covariates), and PFS (P .001 for each of these covariates), respectively.Present results showed that the TC occurred in 12% of LA-SqCLC patients, which was strongly associated with poorer PFS, LRPFS, and OS outcomes after definitive C-CRT.

To evaluate the prognostic value of the Glasgow Prognostic Score (GPS), the combination of C-reactive protein (CRP) and albumin, in glioblastoma multiforme (GBM) patients treated with radiotherapy (RT) and concurrent plus adjuvant temozolomide (GPS).Data of newly diagnosed GBM patients treated with partial brain RT and concurrent and adjuvant TMZ were retrospectively analyzed. The patients were grouped into three according to the GPS criteria: GPS-0: CRP 10 mg/L and albumin 35 g/L; GPS-1: CRP 10 mg/L and albumin 35 g/L or CRP 10 mg/L and albumin 35 g/L; and GPS-2: CRP 10 mg/L and albumin 35 g/L. Primary end-point was the association between the GPS groups and the overall survival (OS) outcomes.A total of 142 patients were analyzed (median age: 58 years, 66.2% male). There were 64 (45.1%), 40 (28.2%), and 38 (26.7%) patients in GPS-0, GPS-1, and GPS-2 groups, respectively. At median 15.7 months follow-up, the respective median and 5-year OS rates for the whole cohort were 16.2 months (95% CI 12.7-19.7) and 9.5%. In multivariate analyses GPS grouping emerged independently associated with the median OS (P 0.001) in addition to the extent of surgery (P = 0.032), Karnofsky performance status (P = 0.009), and the Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) classification (P 0.001). The GPS grouping and the RTOG RPA classification were found to be strongly correlated in prognostic stratification of GBM patients (correlation coefficient: 0.42; P 0.001).The GPS appeared to be useful in prognostic stratification of GBM patients into three groups with significantly different survival durations resembling the RTOG RPA classification.

In a limited prospective data environment of skull base tumors including olfactory neuroblastoma, chordoma, chondrosarcoma, and jugulotympanic paraganglioma, this chapter tries to summarize the worldwide experience from initial admission to follow-up covering the up-to-date multimodality management options of adjuvant, definitive, or palliative intent radiotherapy along with the best possible applicable modality of IMRT, VMAT, SRS, FSRT, and proton-beam therapy.

We aimed to identify the fatal pulmonary hemorrhage- (FPH-) related risk factors in stage 3B/C squamous-cell lung carcinoma (SqCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT). Medical records of 505 stage 3B/C SqCLC patients who underwent 66 Gy radiotherapy plus 1-3 cycles of concurrent chemotherapy with available pretreatment thoracic computerized tomography scans were retrospectively analyzed. Primary end-point was the identification of FPH-related risk factors. Examined factors included the basal patient and tumor characteristics with specific emphasis on the tumor cavitation (TC) status, tumor size (TS) and cavitation size (CS), tumor volume and cavitation volume (TV and CV), relative cavitation size (RCS = CS/Ts), and relative cavitation volume (RCV=CV/TV). FPH emerged in 13 (2.6%) patients, with 12 (92.3%) of them being diagnosed 0.14 (37.5% versus 11.1% for RCV 0.14. Diagnosis of >90% FPHs, NA

PURPOSE To evaluate the radioprotective efficacy of amifostine on irradiated mature rat retina. METHODS A total of 108 Wistar albino rats were categorized into 3 groups, namely, apoptosis (n = 48), acute effects (n = 40), and late changes in retinal cell layers (n = 20). Each group was further subcategorized into 4 arms: control, amifostine (A), radiotherapy + placebo (RT), and RT + A arms, respectively. Intraperitoneal amifostine (260 mg/kg) was administrated to A and RT + A arms 30 minutes before irradiation. Control and A groups were sham-irradiated, whereas a single dose of 20 Gy whole-cranium irradiation was delivered to RT and RT + A arms. Apoptosis was assessed in 8, 12, and 18 hours after irradiation. Electron microscope was used 2 weeks after irradiation for evaluation and scoring of early morphologic changes in retina. Late effects were assessed and scored accordingly by using both the electron and the light microscope on Week 10. RESULTS At acute phase, although no notable change was seen in 8 hours, significant increase in apoptosis was detected in 12 hours in RT arm (P = 0.029). Comparative analyses between the groups in 3 different time points displayed a higher apoptotic rate in RT group than the RT + A group (P = 0.008). Similarly, comparisons between groups for late effects on the basis of electron microscopic findings revealed lower scores in the RT + A than the RT arm (P < 0.001). CONCLUSION This study suggested a potential radioprotective role for amifostine on mature rat retina by reducing radiation-induced apoptosis in retinal cells. These results form a basis for such preclinical investigations and call for future clinical studies.

Chemoradiotherapy is the current standard of care in patients with advanced inoperable stage IIIA or IIIB non-small cell lung cancer (NSCLC). Three-dimensional radiotherapy (3DCRT) has been a trusted method for a long time and has well-known drawbacks, most of which could be improved by Intensity Modulated Radiotherapy (IMRT). IMRT is not currently the standard treatment of locally advanced NSCLC, but almost all patients could benefit to a degree in organ at risk sparing, dose coverage conformality, or dose escalation. The most critical step for a radiation oncology department is to strictly evaluate its own technical and physical capabilities to determine the ability of IMRT to deliver an optimal treatment plan. This includes calculating the internal tumor motion (ideally 4DCT or equivalent techniques), treatment planning software with an up-to-date heterogeneity correction algorithm, and daily image guidance. It is crucial to optimise and individualise the therapeutic ratio for each patient during the decision of 3DCRT versus IMRT. The current literature rationalises the increasing use of IMRT, including 4D imaging plus PET/CT, and encourages the applicable knowledge-based and individualised dose escalation using advanced daily image-guided radiotherapy.

Highlights • SBRT provides a satisfying local control rate of 88% in patients with spMets. • Post-SBRT vertebral compression rate of 4% corresponds to the current literature. • >6 months of bisphosphonates use is associated with lower fracture-free survival., Purpose We aimed to retrospectively assess the incidence of vertebral compression fractures (VCF), examine clinicopathologic factors potentially associated with VCF, and evaluate treatment response in patients who received stereotactic body radiotherapy (SBRT) for spine metastases (spMets). Methods and Materials We identified 78 patients with 125 spMets at baseline and subsequent assessments. Patients received SBRT doses of 16 or 18 Gy. Patients with pre-existing VCF and co-existing local progression were excluded. Spine instability neoplastic score (SINS) was used for spMets categorization. Response to SBRT and VCF were assessed according to the Positron Emission tomography Response Criteria In Solid Tumors (PERCIST) and Genant scores, respectively. Kaplan–Meier analyses were used to assess local control of disease and vertebral compression fracture-free survival (FFS). Results We treated 103 cases with single spMets and 11 cases involving double spMets with SBRT. Progressive disease was reported in 3.2% and 8.2% of the cases in the first and last PET/CT reports, respectively. The distribution of treatment response in the remaining patients was: complete response in 30.6% of patients, partial response in 47.1% of patients, and stable disease in 22.3% of patients in the first PET/CT; complete response in 62.3% of patients, partial response in 16.7% of patients, and stable disease in 21% of patients at the last monitoring. Local failures were observed in 15 (12%) of cases. Median SINS was 5 (range: 1−13); majority of patients in our cohort (70.4%) were categorized as stable according to SINS, five (4%) patients had Grade 3 VCF at a median time of 16 months after SBRT (range: 2−22 months), and 60% of VCF occurred after an interval of at least 12 months after SBRT. No bisphosphonate usage was significantly associated with VCF (r = −0.204; p = 0.022). Median FFS was 21 months. Univariate analyses indicated that female gender (p 6 months of bisphosphonates use (p = 0.002), and the lowest vertebral body collapse score (p = 0.023) were associated with higher FFS. Female gender (p = 0.007), >6 months of bisphosphonates usage (p = 0.018), and the lowest vertebral body collapse score (p = 0.044) retained independent significance. Conclusions This study demonstrated that spine SBRT with doses of 16–18 Gy promises good local control of disease with acceptable VCF rates. Lowest vertebral body collapse score, female gender, and >6 months of bisphosphonate use were significantly associated with longer FFS.

The impact of [18F]fluorodeoxyglucose-positron emission tomography (PET)/computed tomography (CT) restaging on management decisions and outcomes in patients with locally advanced pancreatic carcinoma (LAPC) scheduled for concurrent chemoradiotherapy (CRT) is examined. Seventy-one consecutive patients with conventionally staged LAPC were restaged with PET/CT before CRT, and were categorized into non-metastatic (M0) and metastatic (M1) groups. M0 patients received 50.4 Gy CRT with 5-fluorouracil followed by maintenance gemcitabine, whereas M1 patients received chemotherapy immediately or after palliative radiotherapy. In 19 patients (26.8%), PET/CT restaging showed distant metastases not detected by conventional staging. PET/CT restaging of M0 patients showed additional regional lymph nodes in 3 patients and tumors larger than CT-defined borders in 4. PET/CT therefore altered or revised initial management decisions in 26 (36.6%) patients. At median follow-up times of 11.3, 14.5, and 6.2 months for the entire cohort and the M0 and M1 cohorts, respectively, median overall survival was 16.1, 11.4, and 6.2 months, respectively; median locoregional progression-free survival was 9.9, 7.8, and 3.4 months, respectively; and median progression-free survival was 7.4, 5.1, and 2.5 months, respectively (P

Introduction: The aim of this study was to compare computed tomography (CT)- and positron emission tomography (PET)/CT-based gross tumor volume (GTV) delineation and its subsequent expansion to the planning target volume (PTV), and to analyze the resultant doses of 3-dimensional conformal radiotherapy (3D-CRT) to critical organs. Methods: 15 patients with unresectable extrahepatic cholangiocarcinoma (EHCC) were enrolled into this study. PTVCT-based plans were initially made, and then PTVPET-CT-based plans were created using the same beam angles and isocenter. The dosimetric parameters analyzed included GTVCT, PTVCT, GTVPET-CT and PTVPET-CT. Prescribed and delivered radiation doses to target volumes and delineated organs at risk were also compared. Results: Mean GTV and PTV were significantly reduced in the PET/CT-based plan compared to the CT-based plan; the mean reductions of GTV and PTV were 28.7% and 15.2%, respectively. The mean value for GTVPET/GTVCT mismatch was 49.5 ± 28.9%, and that for GTVCT/GTVPET was 95.9 ± 19.5%. The mean value for PTVPET-CT/PTVCT mismatch was 21.9 ± 7.0% and that for PTVCT/PTVPET-CT was 39.1 ± 9.2%. Liver doses were significantly reduced (17.1%) in the PET/CT-based plan compared to the CT-based plan; the doses received by at least 30% and 50% of the liver were 30.0%, and 27.3%, respectively. Conclusion: The potential benefit of PET/CT is the reduction in geographic misses and regional treatment failures associated with CT-based planning.

Background: Anaplastic astrocytoma (AA; WHO grade-III) patients determination of prognostic factors helps generating multimodal therapy protocols. For this purpose, in the Baskent University, Adana Medical Research Center, specific characteristics of AA patients who have surgery were retrospectively investigated and factors which affect prognosis has been determined. Patients and Methods: Between January 2005 and 2009, 20 patients who have AA have been evaluated retrospectively. Totally, 20 patients had 31 operations. Sixteen patients had only adjuvant radiation therapy (RT). In the postoperative period, 8 patients received adjuvant RT. Nine of 10 patients with tumor recurrence received concomitant therapy with temozolomide (ConcT with TMZ) protocol. No adjuvant therapy protocol could be applied in three patients with poor general condition in the postoperative period. Results: Median survival for patients died was 16±17 months; one year survival was 75% and five year survival 25%. After univariate analysis, preoperative Karnofsky performance score (KPS) was ≥80 ( P=0.005577FNx01), postoperative KPS was ≥80 ( P=0.003825FNx01), type of tumor resection ( P=0.001751FNx01), multiple operations ( P=0.006233FNx01), and ConcT with TMZ protocol ( P=0,005766FNx01) were all positive prognostic factors which extend the survival. Conclusions: The results of the multivariate analysis did not put forward an independent prognostic factor acting on the survival period ( P>0.05).

Weight loss (WL), as a key step of the irreversible and fatal cancer-related anorexia cachexia syndrome is present to some degree in 80% of non-small cell lung cancer (NSCLC) patients upon diagnosis which has been clearly proved to negatively alter patients' performance status, quality of life (QOL), response to treatment, and prognosis. However, WL is not a problem encountered only upon diagnosis but is also commonly reported during the course of aggressive chemotherapy, radiotherapy (RT) and particularly the concurrent chemoradiotherapy (C-CRT) which may further diminish QOL measures and clinical outcomes. In general, the NSCLC literature has concentrated on WL during the treatment course, but recent studies have demonstrated that it is possible to preserve or even experience weight gain (WG) during or just short after the discontinuation of various cancer treatments in approximately 40% to 45% NSCLC patients. Considering the fact that recent evidence suggest a prognostic and predictive role for WG in anticipation of longer survival times and better response rates in weight gainers, this current manuscript will specifically aim to realize the actual value of WG in locally advanced and metastatic NSCLC patients which may potentially be added to the conventional prognostic and predictive factors as a novel surrogate marker of outcomes in such patients.

Background: Trichilemmal carcinoma (TLC) is a rare adnexal malignant tumor developing from the outer root sheath of hair follicles with no distinct clinical features which might clinically be misdiagnosed as actinic keratosis, nodular melanoma, basal or squamous cell carcinoma. Albeit no consensus exists on standard treatment of TLC, tumor excision with adequate clear margins is the current widely accepted treatment consideration with no previous literature on use of radiotherapy (RT) in definitive or postoperative settings. Case presentation: A 60-year-old woman who was repeatedly treated with cryotherapy located on her left nasal alae for an initial diagnosis of actinic keratosis and diagnosed as TLC at last surgery was referred for RT of microscopic surgical margins. The patient was treated with 6 MeV electron beam RT prescribed to surgical bed plus 1-cm margins at all directions, namely the planning target volume. The total and per fraction doses were 60 and 2 Gy, respectively, which is commonly practiced for any skin tumor with positive margins. The treatment was well tolerated with no acute or chronic complications. The patient was alive with no local, regional, or distant recurrences at the 49 months of her follow-up. Conclusions: Although the follow-up period is relatively short and further evidence is needed to confirm the exact role of RT in adjuvant treatment of TLC, the outcomes of present rare case of a nasal TLC suggests that adjuvant RT in patients with positive surgical margins may provide satisfactory local tumor control.

Thymic tumors, defined as neoplasms of thymic epithelial cells, are the most common anterior mediastinal tumors in adults (approximately 20 % of anterior mediastinal tumors) with heterogeneous biological, oncological, and histological characteristics. The incidence is frequent between the fourth and sixth decades (Lewis et al. Cancer 60(11):2727–2743, 1987). No risk factors are evident aside from strong correlation with myasthenia gravis and other paraneoplastic syndromes (Safieddine et al. J Thorac Oncol: Off Publ Int Assoc Study Lung Cancer 9(7):1018–1022, 2014). Aside from diagnosis by chance in a chest X-ray or computerized tomography (CT) scan or diagnosis based on paraneoplastic syndromes like myasthenia gravis (MG, approximately 45 % of thymomas) and thymoma that was found in 10–15 % of MG cases (Muller-Hermelink et al. Ann NY Acad Sci 681:56–65, 1993; Detterbeck and Parsons Annals Thorac Surg 77(5):1860–1869, 2004), local pressure symptoms such as chest pain, dyspnea, coughing, and venous congestion could lead to the diagnosis of thymoma or thymic carcinoma. Invasive thymomas and thymic carcinomas consist of only 0.2–1.5 % among all thymic tumors, and radiotherapy could play an important role in their treatment due to their radiosensitivity; however, their low incidence and slow natural growth increase the difficulty to delineate the role of radiotherapy aside from the retrospective series in the literature.

During the last decade, technology has provided remarkable improvements and accessibility to cutting edge techniques in many departments. The major goal is set to improve quality of life and toxicity profiles of mediastinal treatments without compromising the local control and overall survival. Moving from 2D to 3D and 4D simulation has exposed the secrets of moving targets to individualize margins on specified targets and organs at risk, in addition to ensure precision to minimize the interobserver variability in target delineation via incorporation of FDG–PET fusion in customization. Image-guided radiotherapy with either planar or volumetric imaging increased accurate and appropriate daily localization, promoting comfort to encourage dose escalation or respiratory phase-specific treatment strategies along with motion management in thoracic malignancies. As randomized trials are lacking for many new technologies, knowledge-based tailoring and implementation of any site and stage-specific requirement per patient has been a common practice in the recent years, such as SBRT, IMRT, VMAT, or protons.

Although surgical resection is directly related with anatomic boundaries and as a summary an all-or-none modality, even surgical prognosticators to define post-resection functional status could remain suboptimal. Radiotherapy, on the other site, is not an anatomical dissection, not a straightforward modality, and cannot be easily defined in numbers because of lack of correlation of effected anatomic units and heterogeneity of the effect on each unit. So evaluation before radiotherapy is overall a risk assessment with the baseline functional status and radiotherapy-induced expected loss in the function. Radiotherapy-triggered changes are gradual over time, sometimes as unusual reactions or hypersensitivity pneumonitis, and the compensation by the unirradiated lung is unpredictable. Overall, a radiation oncologist is expected to minimize the potential toxicity risks in an environment of various combinations of medical inoperability, poor pulmonary functionality, riskily localized or large parenchyma endangering bulky tumors, etc. and is mostly asked to be prepared to accept potential morbidities in this referred population with great expectations who will face a certain death if not treated.

Brain metastasis (BM) is either present at the initial presentation or emerges somewhere during the treatment course in up to 64 % patients. Therapeutic strategies of BM include chemotherapy, neurosurgery, whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or different combinations of them. In general, the priority of the single- or combination-treatment modality is usually decided in view of the information about the patient’s performance status, extracranial disease status, number, size, total volume, and localization of the BM. Based on the comparative phase III trials, with its high-precision capability in delivery of large doses of RT in a single session, SRS appears to be a noninvasive alternative to neurosurgery for single BM. Similarly, available data suggests almost equal effectiveness of SRS in ≤3 versus >3 BM situations. Therefore, in lack of any documented evidence suggesting inefficacy of SRS in patients with >3 BM, it is reasonable to offer SRS for suitable patients with larger BM. Tumor bed SRS (TB-SRS) is a relatively new treatment approach with no randomized data published to date. Available literature on use of TB-SRS is encouraging, but much is still unknown about the required doses and optimal margins, which underlines the need for appropriately designed future studies on this highly specific issue. Clinically, SRS alone results in better neurocognitive functions compared to WBRT and is equivalent to neurosurgery with no overall survival differences compared to these treatment options. Therefore, SRS alone can be safely utilized in particular patients with close follow-ups for distant brain recurrences. Technically, SRS can be performed in various ways by using Gamma Knife or high-capacity novel linear accelerators. Absolutely some technical differences exist among diverse SRS hardware and related treatment planning systems with associated pros and cons, but available comparative outcomes do not suggest any differences in clinical outcomes including the tumor control and survival rates, as long as the fundamental tenets of SRS are pursued.

Small-cell lung cancer (SCLC) represents for approximately 10–15 % all lung cancers. Typically, SCLC presents in senior patients (>70 years) with a substantial smoking history. According to historic Veteran’s Administration Lung Study Group staging criteria, SCLC is simply divided into two respective stages: limited stage (LS-SCLC) and extensive stage SCLC (ES-SCLC). Despite fundamental improvements in imaging and treatment modalities, prognosis of SCLC patients is still poor with median survival ranges of only 15–20 months for LS-SCLC and 8–13 months for ES-SCLC. Unless diagnosed quite early, which constitutes only less than 5 % of all SCLC patients, surgery currently has little or almost no role in the standard management of SCLC. Therefore, surgery is recommended for only medically fit stage I SCLC patients with peripherally located lesions. Based on the results of multiple randomized controlled trials and/or meta-analyses, the optimal treatment of LS-SCLC is cisplatin-etoposide (EP)-based concurrent chemoradiotherapy (45 Gy b.i.d thoracic radiotherapy) followed by prophylactic cranial irradiation (PCI: 25 Gy in ten fractions) for every patients with any objective response after chemoradiotherapy. Similarly, evidence-based treatment of ES-SCLC includes EP combination chemotherapy followed by thoracic radiotherapy and PCI in patients with any objective response. In order to achieve best results, the thoracic radiotherapy and chemotherapy should be integrated as soon as possible (preferably at first course of chemotherapy), and the overall interval between the start of chemotherapy and the completion of thoracic radiotherapy should be kept as short as possible, namely

Retinoblastoma (RB) is the most common orbital tumor of childhood. Treatment strategy depends on number, loalization and extent of disease (unilateral vs bilateral) involvement. Currently, significant improvements in treatment and long survival rates have been achieved in management of this tumor group that mandates for search of more sophisticated novel treatment modalities to reduce the risks of treatment related side effects and secondary malignancies. In recent years, both the role and techniques of radiation therapy (RT) have significantly changed in parallel to the improvements in technology. Present review aims to discuss the current treatment modalities in RB, and the role and alternative techniques of RT in the light of recent literature.

In this study, we investigated the shrinking effect of concurrent three-dimensional conformal radiotherapy (3D-CRT) and androgen deprivation (AD) on prostate volume, and its possible impact on the dose received by the rectum and bladder during the course of 3D-CRT. The difference between the prostatic volumes determined on pre-treatment planning CT (PL-CT) and post-treatment CT (PT-CT) following a 3D-CRT course was assessed in 52 patients with localised prostate carcinoma. The changes in mean prostate volume when compared with PL-CT and PT-CT-based measurements were assessed. The pre- and post-treatment mean prostate volumes for the whole study population were 49.7 cm(3) and 41.0 cm(3) (p _ 0.02), respectively. The study cohort was divided into two groups depending on the duration of neoadjuvant androgen deprivation (NAD): 23 patients (44.7%) were designated as "short NAD" (or =3 months; SNAD) and the remaining 29 (55.3%) as "long NAD" (3 months; LNAD). Patients on SNAD experienced a significantly greater reduction in prostate volume compared with those on LNAD (14.1% vs 5.1%; p _ 0.03). A significant increase in rectum V(40-60) values in PT-CT compared with PL-CT was demonstrated. LNAD patients had significantly higher rectal V(50-70) values at PT-CT compared with the SNAD group. There was a significant decline in V(30)-V(75) bladder values in PT-CT compared with PL-CT in the SNAD group. In conclusion, a higher prostate volume reduction during 3D-CRT was demonstrated when RT planning was performed within 3 months of NAD. However, this reduction and daily organ motion may lead to an unpredictable increase in rectal doses.

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.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.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 of35% had a 31% risk of ARIE grade 2 or 3, and the risk increased to 76% with a V55 ofor=35% (p=0.01).This schedule and dosage of glutamine may be beneficial in the prevention of ARIE and weight loss in lung cancer patients undergoing thoracic irradiation.

To assess the impact of the presence and degree of pretreatment weight loss (WL) on the survival of locally-advanced pancreas cancer (LAPC) patients treated with concurrent chemoradiotherapy (C-CRT).Seventy-three patients who received 50.4 Gy C-CRT were analyzed. All patients underwent laparoscopy (n = 18) or laparotomy (n = 55), and biopsies were obtained for histologic examination of the primary tumor and enlarged/metabolically active regional lymph nodes. Pretreatment WL and percentage WL (PWL) were calculated by utilizing data obtained 6 months prior to and during hospital admission. The primary objective was to assess the influence WL status on overall survival (OS), and the secondary objective was the identification of a PWL cut-off value, if available.Forty-five (61.6%) patients had WL. Median OS was 14.4 months for the entire study population which was significantly longer in the non-WL than the WL cohort (21.4 vs. 11.3 months; p 0.003). On further analysis a cut-off value of 3.1% was identified for WL. Accordingly, patients with WL 3.1% had significantly longer OS than those with WL ≥ 3.1% (25.8 vs. 10.1 months; p 0.001). In multivariate analysis, both the WL status (p 0.001) and PWL (p = 0.002) retained their independent significance.Both the presence and degree of WL prior to C-CRT had strong adverse effects on the survival of LAPC patients, even if they presented with a BMI 20 kg/m(2). Additionally, a WL of ≥3.1% in the last 6 months appeared to be a strong cut-off for the stratification of such patients into distinctive survival groups.

AIM: In this study, factors affecting survival, local failure, distant brain failure, whole brain failure and whole-brain radiation therapy (WBRT) free survival according to histological subtypes were investigated in patients with brain metastases from non-small cell lung cancer (NSCLC). MATERIAL and METHODS: Patients with positive pathology reports for adenocarcinoma (ACA) and squamous cell carcinoma (SCC) were included in the study. Seventy-eight ACA and 26 SCC patients were included in the study. Patients with previous history of cerebral metastasis surgery and WBRT were excluded from the study. RESULTS: The median survival was calculated as 12.6 months for patients with ACA and 5.9 months for patients with SCC. One-year distant brain failure was calculated as 65.1\% in ACA patients and 39.6\% in SCC patients. One-year whole brain failure was calculated as 58.1\% in ACA patients and 39.6\% in SCC patients. The one-year freedom from WBRT rate was calculated as 72.8\% in ACA patients and 56.3\% in SCC patients. SCC histology was considered as a significant factor in deterioration of overall survival in multivariate analysis. SCC histology, the increase in the number of metastases and RPA class were factors that caused an increase in distant brain failure. Also, SCC histology, the increase in the number of metastases and RPA class were factors that caused an increase in whole brain failure. CONCLUSION: SCC histology may be an important prognostic factor for overall survival. Also, due to high distant brain failure rate in SCC histology, WBRT can be added to treatment early.

We retrospectively investigated the impact of weight change (WC) during concurrent chemoradiation therapy (C-CRT) on clinical outcomes of stage 3B non-small cell lung cancer (NSCLC) patients.A total of 425 patients treated with C-CRT were included. All patients received 60 to 66 Gy of thoracic radiation therapy concurrently with 1 to 3 cycles of platinum-based chemotherapy. Pre- and posttreatment weight measurements on first and last days of C-CRT were used for WC. Patients were divided into 2 groups: group 1=weight loss (WL); group 2=weight preservation/gain (WP) for comparative analyses.Following C-CRT, 252 patients (59.3%) experienced WL, while 89 patients (20.9%) and 84 patients (19.8%) showed WP or WG. At median 24.2 months of follow-up, 142 patients (33.4%) were alive (84 WP [48.6%] and 58 WL [23.0%]), and 58 (13.6%) of them were free of disease progression (41 [23.7%] for WP and 17 [6.7%] for WL). Median overall survival (OS), locoregional progression-free survival (LRPFS), progression-free survival (PFS), and distant metastases-free survival (DMFS) for the entire population were 22.8, 14.4, 10.6, and 11.7 months, respectively. Intergroup comparisons between WP and WL cohorts revealed significantly superior OS, LRPFS, PFS, and DMFS in WP patients (P.05 for each). On multivariate analyses, only WL and advanced T stage were associated with poor prognosis (P.05).Present results in 425 stage 3B NSCLC patients demonstrated that WL during C-CRT is strongly associated with inferior survival outcomes compared to WP. This emerging finding might be useful by forming an encouraging basis for future investigations in facilitating a way to improve the outcomes of these patients experiencing WL during C-CRT.

Background We evaluated influence of limited-field radiotherapy with no elective nodal irradiation (ENI) on outcomes and toxicity profile in patients with locally advanced pancreatic adenocarcinoma (LAPAC), treated with definitive concurrent chemoradiotherapy (C-CRT). Methods Thirty-five patients with histological proof of LAPAC underwent 50.4 Gy of C-CRT with 5-FU followed by maintenance gemcitabine. Target volume included primary tumor and lymph nodes that appeared to be involved on either contrast-enhanced computerized tomography or 18F-fluoro-deoxyglucose positron emission tomography. Results No grade 4/5 acute/late toxicity was reported at median 15.7 months. Acute hematologic plus non-hematologic grade 3 toxicity was noted in 10 (28.6%) patients. At long-term, 2 patients (5.7%) experienced grade 3 gastric outlet obstructions at 8.7 and 10.9 months, respectively. No isolated regional relapses were noted. Median overall-survival (OS), progression-free survival (PFS), and locoregional-PFS (LRPFS) were 15.2, 9.1 and 7.3 months, respectively. Corresponding 1- and 2-year survival estimates were 60.0% and 20.0% for OS, 41.9% and 17.4% for LRPFS, and 34.0% and 12.7% for PFS, respectively. Conclusions Compared to ENI literature, first report of a limited-field C-CRT study carried out in Turkey showed that omission of ENI was relatively well tolerated without compromising survival and locoregional control rates in patients with LAPAC.

Worldwide, lung carcinoma (LC) is the commonest and deadliest form of cancer in men and women, exceeding the mortality of prostate, breast, and colorectal cancers combined (Jemal et al., 2009). Irrespective of histologic subtype, more than 90% of all LC is strongly associated with cigarette smoking (Alavanja et al., 2002), and the risk significantly increases with the number of cigarettes smoked per day, degree of inhalation, age at initiation, and life-long cumulative exposure (Tyczynski et al., 2003). Although survival at 5-year is less than 15%, yet, there exists no single proven chemopreventive measure reducing the risk of LC development, except for cessation of cigarette smoking. Histologically, non-small cell LC (NSCLC) and small-cell LC (SCLC) are the two commonest types of LC, constituting 85-90% and 10-15% of all cases, respectively (Rosenzweig et al., 2010). SCLC (previously called oat cell carcinoma) is relatively less common than NSCLC; however, because of a more aggressive growth pattern and clinical course, its treatment is more challenging. Although there is no significant difference in outcome by histologic subtype, the World Health Organization classification subdivides SCLC into three cell types; pure or classic, variant cell, and mixed (Brambilla et al., 2001). SCLC displays a high propensity to metastasize, and usually a remarkable but temporary responsiveness to chemotherapy and radiotherapy (RT). Although some may be cured, most patients succumb to disease because of rapid development of drug resistance and resultant disease progression. Median survival for metastatic SCLC is only 10 months, which is interestingly very similar to patients with relatively much more drug resistant NSCLC of similar stage (Chute et al., 1997). Despite great improvements in imaging, pathology, genetics, chemotherapy, and RT techniques, this did not translate into the clinical outcomes, thus, the current overall survival rate for SCLC patients is not different than that was 20 years before (Chute et al., 1997). This chapter has been designated to focus specifically on treatment of SCLC patients, with specific emphasises on the technical basis and outcomes of current RT and concurrent chemoradiotherapy (C-CRT). Therefore, readers interested in more comprehensive information about the epidemiology, etiology, preventive measures, pathologic and genetic basis and surgical treatment of SCLC are referred to excellent reviews available in this book.

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.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.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; p0.0001), treatment end (29.9 ± 8.8 μmol/l; p0.0001), 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 (p0.0001). 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.Citrulline-based assessment scores are objective and should be considered in measuring radiation-induced intestinal toxicity.

BACKGROUND To evaluate pathologically confirmed incidence of pseudoprogression and its impact on survival in glioblastoma multiforme (GBM) patients treated with radiotherapy and concurrent temozolomide (TMZ), followed by 6 months of TMZ maintenance therapy. MATERIALS AND METHODS Sixty-three patients with histologic proof of GBM underwent 60 Gy (2 Gy/fr, 30 fractions) of brain radiotherapy concurrent with continuous 75 mg/m/d TMZ, followed by 6 cycles of maintenance TMZ (200 mg/m/d for 5 d, every 28 d). Response assessment was performed by magnetic resonance imaging every 2 months. All patients with radiologic doubt of early tumor progression (≤6 mo) underwent salvage surgery. RESULTS All patients underwent surgical resection. Gross total, subtotal resection, and biopsy were performed in 17 (27.0%), 32 (51.6%), and 14 (21.4%) patients, respectively. Lesion enlargement on first follow-up magnetic resonance imaging evidenced in 28 (44.4%) patients. Salvage pathologies revealed pseudoprogression in 12 of 28 (42.8%) patients corresponding to an overall pseudoprogression rate of 19%. Survival analysis revealed that patients with pseudoprogression had superior overall and progression-free survival rates at both 1 and 2 years (P

Background When combined with adequate tumoricidal doses, accurate target volume delineation remains to be the one of the most important predictive factors for radiotherapy (RT) success in locally advanced or medically inoperable malignant pleural mesothelioma (MPM) patients. Recently, 18-fluorodeoxyglucose positron emission tomography (PET) has demonstrated significant improvements in diagnosis and accurate staging of MPM. However, role of additional PET data has not been studied in RT planning (RTP) of patients with inoperable MPM or in those who refuse surgery. Therefore, we planned to compare CT with co-registered PET-CT as the basis for delineating target volumes in these patients group. Methods Retrospectively, the CT and co-registered PET-CT data of 13 patients with histologically proven MPM were utilized to delineate target volumes separately. For each patient, target volumes (gross tumor volume [GTV], clinical target volume [CTV], and planning target volume [PTV]) were defined using the CT and PET-CT fusion data sets. The PTV was measured in two ways: PTV1 was CTV plus a 1-cm margin, and PTV2 was GTV plus a 1-cm margin. We analyzed differences in target volumes. Results In 12 of 13 patients, compared to CT-based delineation, PET-CT-based delineation resulted in a statistically significant decrease in the mean GTV, CTV, PTV1, and PTV2. In these 12 patients, mean GTV decreased by 47.1% ± 28.4%, mean CTV decreased by 38.7% ± 24.7%, mean PTV1 decreased by 31.1% ± 23.1%, and mean PTV2 decreased by 40.0% ± 24.0%. In 4 of 13 patients, hilar lymph nodes were identified by PET-CT that was not identified by CT alone, changing the nodal status of tumor staging in those patients. Conclusion This study demonstrated the usefulness of PET-CT-based target volume delineation in patients with MPM. Co-registration of PET and CT information reduces the likelihood of geographic misses, and additionally, significant reductions observed in target volumes may potentially allow escalation of RT dose beyond conventional limits potential clinical benefits in tumor control rates, which needs to be tested in future studies.

Background To evaluate the impact of four different rectum contouring techniques and rectal toxicities in patients with treated with 3D conformal radiotherapy (3DCRT). Methods Clinical 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. Results Median 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). Conclusion Different 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.