Search

At initial presentation, approximately 10–14 % of small-cell lung carcinoma (SCLC) patients manifest with radiologically evident brain metastases (BM) which arises up to 69 % at 2 years. Similarly, brain failures are reported in 21–54 % of all non-small-cell lung carcinoma (NSCLC) patients, and of these, the brain is the first site of relapse in 15–30 % cases. Although significant improvements have been achieved in local and distant control of both SCLC and NSCLC as a result of implementation of aggressive treatment modalities, unfortunately such aggressive treatments proved no noteworthy viability in lessening of overall brain or brain as the first site of relapse rates. Regarding its counteractive actions on BM emergence, the potential beneficial effects of prophylactic cranial irradiation (PCI) in patients with limited-stage SCLC (LS-SCLC), extensive-stage SCLC (ES-SCLC), and locally advanced NSCLC (LA-NSCLC) have been addressed with several randomized trials and meta-analysis. Based on the results of these investigations, PCI of 25 Gy (2.5 Gy in ten fractions) should be recommended for all medically fit LS- and ES-SCLC patients with any objective response to primary therapy in order to reduce BM incidence rates and to prolong OS times. Although the PCI studies in LA-NSCLC patients suggest significant reductions in BM incidence rates with PCI, yet in the absence of an established survival benefit, it is currently quite difficult to recommend its routine use in LA-NSCLC patients. However, future studies involving high-risk patients may prove worthy in determination of the exact impact if they are needed in order to reliably comment on the issue of PCI in LA-NSCLC patients.

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

To retrospectively assess the influence of prophylactic cranial irradiation (PCI) timing on brain relapse rates in patients treated with two different chemoradiotherapy (CRT) regimens for Stage IIIB non-small-cell lung cancer (NSCLC).A cohort of 134 patients, with Stage IIIB NSCLC in recursive partitioning analysis Group 1, was treated with PCI (30 Gy at 2 Gy/fr) following one of two CRT regimens. Regimen 1 (n = 58) consisted of three cycles of induction chemotherapy (ICT) followed by concurrent CRT (C-CRT). Regimen 2 (n = 76) consisted of immediate C-CRT during thoracic radiotherapy.At a median follow-up of 27.6 months (range, 7.2-40.4), 65 patients were alive. Median, progression-free, and brain metastasis-free survival (BMFS) times for the whole study cohort were 23.4, 15.4, and 23.0 months, respectively. Median survival time and the 3-year survival rate for regimens 1 and 2 were 19.3 vs. 26.1 months (p = 0.001) and 14.4% vs. 34.4% (p.001), respectively. Median time from the initiation of primary treatment to PCI was 123.2 (range, 97-161) and 63.4 (range, 55-74) days for regimens 1 and 2, respectively (p0.001). Overall, 11 (8.2%) patients developed brain metastasis (BM) during the follow-up period: 8 (13.8%) in regimen 1 and 3 (3.9%) in regimen 2 (p = 0.03). Only 3 (2.2%) patients developed BM at the site of first failure, and for 2 of them, it was also the sole site of recurrence. Median BMFS for regimens 1 and 2 were 17.4 (13.5-21.3) vs. 26.0 (22.9-29.1 months), respectively (p0.001).These results suggest that in Stage IIIB NSCLC patients treated with PCI, lower BM incidence and longer survival rates result from immediate C-CRT rather than ITC-first regimens. This indicates the benefit of earlier PCI use without delay because of induction protocols.

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.

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.

Amaç: Bu çalışmada lokal ileri rektum kanserli hastalarda neoadjuvan kemoradyoterapi öncesi basit uygulanabilir, en temel parametrelerden birisi olan hemoglobin (Hb) seviyesi ile genel sağkalım arasındaki ilişkiyi araştırmayı amaçladık.Gereç ve Yöntem: Neoadjuvan kemoradyoterapi tedavisi sonrasında cerrahi uygulanan 123 lokal ileri rektum kanseri tanılı hasta retrospektif olarak çalışmamızda değerlendirildi. Tüm hastaların tedavi öncesi Hb değerleri bağımsız değişken olarak kaydedildi. Birincil amacımız tedavi Hb seviyesinin genel sağkalıma etkisi olarak belirlendi. Bulgular: Çalışmanın ortalama izlem süresi 40,3 ay (1,4-92ay) olarak tespit edildi. Yapılan ROC analizine göre Hb’nin cut-off değeri 12.5g/dl (AUC=0,673, %95 0.564-0.781) bulundu. Grup Hb’nin cut-off değerine göre normal-Hb (nHb; Hb>12) ve düşük-Hb (dHb≤12) iki gruba ayrıldığında nHb olan grupta Hb’ni düşük olan gruba göre genel sağkalım istatistiksel olarak daha uzun saptandı. Çok değişkenli analizde de p değeri anlamlılığını korudu.Sonuç: Neoadjuvan kemoradyoterapi tedavisi planlanan lokal ileri rektum kanseri tanılı hastalarda tedavi öncesi Hb değerinin bağımsız bir prognostik faktör olduğu düşünüldü., Purpose: This study aims to systematically evaluate the relationship between baseline blood count levels, simply and basically initiated, and treatment response in locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy.Materials and Methods: This retrospective study included 123 locally advanced rectal cancer patients who were treated with neoadjuvant chemoradiotherapy followed by surgery. Pretreatment Hb level was assessed as an independent variable for the whole study sample .The primary endpoint was the impact of pre-treatment Hb levels on overall survival. Results: At a median follow-up of 40,3 months (1,4-92 months). A Hb cut-off value of 12.5 g/dl (AUC=0.673, %95 0.564-0.781) was identified by using ROC analysis. Following the stratification of patients at this cut-off point into two groups: normal-Hb (nHb; Hb>12) and low-Hb (dHb≤12), the comparative survival analysis demonstrated that the patients in the nHb group had significantly increased OS than those in the dHb group, and retained its independent significant association with survival outcomes in the multivariate analysis. Conclusion: Knowledge of pretreatment hematological parameters appears to be an important prognostic factor in patients with rectal carcinoma.

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.

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

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.

A 44-year-old male who has 20 pack/year smoking history with no significant past medical history presented with a painful mass in his right upper neck, which had gradually enlarged for nearly 8 months. He had no problems with dysphagia, swallowing, chewing, phonation as well as any chest pain, palpitations, or dyspnea.

To investigate the safety and efficacy of single-dose 8-Gy palliative chest reirradiation (CRI) in metastatic non-small cell lung cancer (M-NSCLC) patients with painful thoracic failures (TF) within the previous radiation portal.We retrospectively analyzed the clinical data of 78 M-NSCLC patients who received single-dose 8-Gy CRI for painful TF after concurrent chemoradiation therapy to a total radiation dose of 52 to 66 Gy between 2007 and 2012. Primary endpoints included significant pain relief (SPR) defined as a ≥2 point decrement in the Visual Analogue Scale for Pain inventory (VAS-P), time to pain relief, and duration of pain control. Secondary objectives were survival and prognostic factors.Treatment was well tolerated, with only 5.1% grade 3 pneumonitis and 1.3% grade 2 esophagitis. Pre-CRI median and post-CRI minimum VAS-P were 7 and 3 (P.001), respectively. SPR was noted in 67 (85.9%) patients, and only 3 (3.9%) scored progressive pain. Median time to lowest VAS-P and duration of pain control were 27 days and 6.1 months, respectively. Median overall survival (OS) was 7.7 months, and the 1-year OS rate was 26.5%. On multivariate analyses, lower Eastern Cooperative Oncology group score (1-2; P.001), absence of anemia (P=.001), and fewer metastatic sites (1-2; P.001) were found to be associated with longer OS.Single-dose 8-Gy CRI provides safe, effective, and durable pain palliation for TF in radically irradiated M-NSCLC patients. Because of its convenience, lower cost, and higher comfort, the present protocol can be considered an appropriate option for patients with limited life spans.

Aims and Background To investigate the objective utility of our clinical routine of reproducible deep-inspiration breath-hold irradiation for left-sided breast cancer patients on reducing cardiac exposure. Methods and Study Design Free-breathing and reproducible deep-inspiration breath-hold scans were evaluated for our 10 consecutive left-sided breast cancer patients treated with reproducible deep-inspiration breath-hold. The study was based on the adjuvant dose of 50 Gy in 25 fractions of 2 Gy/fraction. Both inverse and forward intensity-modulated radiotherapy plans were generated for each computed tomography dataset. Results Reproducible deep-inspiration breath-hold plans with forward intensity-modulated radiotherapy significantly spared the heart and left anterior descending artery compared to generated free-breathing plans based on mean doses – free-breathing vs reproducible deep-inspiration breath-hold, left ventricle (296.1 vs 94.5 cGy, P = 0.005), right ventricle (158.3 vs 59.2 cGy, P = 0.005), left anterior descending artery (171.1 vs 78.1 cGy, P = 0.005), and whole heart (173.9 vs 66 cGy, P = 0.005), heart V20 (2.2% vs 0%, P = 0.007) and heart V10 (4.2% vs 0.3%, P = 0.007) – whereas they revealed no additional burden on the ipsilateral lung. Reproducible deep-inspiration breath-hold and free-breathing plans with inverse intensity-modulated radiotherapy provided similar organ at risk sparing by reducing the mean doses to the left ventricle, left anterior descending artery, heart, V10-V20 of the heart and right ventricle. However, forward intensity-modulated radiotherapy showed significant reduction in doses to the left ventricle, left anterior descending artery, heart, right ventricle, and contralateral breast (mean dose, 248.9 to 12.3 cGy, P = 0.005). The mean doses for free-breathing vs reproducible deep-inspiration breath-hold of the proximal left anterior descending artery were 1.78 vs 1.08 Gy and of the distal left anterior descending artery were 8.11 vs 3.89 Gy, whereas mean distances to the 50 Gy isodose line of the proximal left anterior descending artery were 6.6 vs 3.3 cm and of the distal left anterior descending artery were 7.4 vs 4.1 cm, with forward intensity-modulated radiotherapy. Overall reduction in mean doses to proximal and distal left anterior descending artery with deep-inspiration breath-hold irradiation was 39% (P = 0.02) and 52% (P = 0.002), respectively. Conclusions We found a significant reduction of radiation exposure to the contralateral breast, left and right ventricles, as well as of proximal and especially distal left anterior descending artery with the deep-inspiration breath-hold technique with forward intensity-modulated radiotherapy planning.

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

To compare the protective effects of the potent antioxidants, melatonin and octreotide, against radiation-induced intestinal injury. A total of 42 male 3-month-old Swiss albino mice (40 ± 10 g) were matched according to body weight and randomly assigned to one of six groups: control; radiation treatment (RT) only; melatonin only (15 mg/kg, i.p.); melatonin + RT; octreotide only (50 μg/kg i.p.); and octreotide + RT. Intestinal damage was induced by exposure to a single whole-body radiation dose of 8 Gy. All mice tolerated the experimental interventions, and no deaths were observed. Irradiation induced architectural disorganization, including inflammatory mononuclear cell infiltration, villitis, and desquamation with eosinophilic necrosis, and diminished mucosal thickness, crypt height, and villous height. In the melatonin + RT and octreotide + RT groups, the villous pattern was well preserved; desquamation at villous tips and edema was prominent, but necrosis was absent. The radiation-induced decrease in mucosal thickness was significantly reduced by pretreatment with melatonin (p

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

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.

Sarcomatoid carcinoma is a rare tumor of the urinary bladder accounting for less than 0.5% of all primary urinary bladder tumors. Since the patients were presented with large tumor with extended stages, outcome was found to be poor. In order to improve local control, adjuvant local treatment may be practical. We report a rare case with sarcomatoid carcinoma of the urinary bladder diagnosed with immunuhistochemical (IHC) study and treated with 3D-conformal radiotherapy (3DCRT) post-operatively. A 55-year old female patient complained about painless hematuria for 2 months. Computed tomography of the pelvic region revealed tumor and wall thickening at the left posterolateral side of the bladder. Total cystectomy with lymph node dissection and total abdominal hysterectomy and bilateral salphingo-oopherectomy was performed and histopathological and immunohistochemical findings strongly correlate with sarcomatoid carcinoma. The patient was treated with 3D conformal radiotherapy (3DCRT) with a total dose of 59.4 Gy with 1.8 Gy fractional daily doses. Patient was alive without any local recurrence and distant metastasis 10 months after surgery.

We present an extremely rare case of Woringer-Kolopp disease with CD4+/CD8+ immunohistochemical features in a 27-year-old male patient, which involved the right gluteal region continuing down to the lower thigh. Although the lesions had been present for 15 years, the disease abruptly changed its indolent clinical behavior in the last 3 months and gained local aggressiveness without features of dissemination. The patient was successfully treated with 6 MeV electron-beam radiotherapy and the radiation portal was determined to be the gross lesion plus 1-cm margins around the lesion. Radiation therapy was administered with a hypofractionated dose schedule of 2.8 Gy per fraction in 13 fractions, 5 days a week, to a total of 36.4 Gy. No radiation-induced toxicity was reported during therapy. The patient's follow-up was ordinary with no recurrence after a follow-up period of 38 months and the cosmetic result was excellent.

Background Prophylactic cranial irradiation (PCI) has been demonstrated to reduce or delay the incidence of brain metastases (BM) in locally advanced non-small cell lung carcinoma (LA-NSCLC) patients with various prognostic groups. With this current cohort we planned to evaluate the potential usefulness of prophylactic cranial irradiation (PCI) specifically in recursive partitioning analysis (RPA) Group 1, which is the most favorable group of LA-NSCLC patients. Methods Between March 2007 and February 2008, 62 patients in RPA group 1 were treated with sequential chemoradiotherapy and PCI for stage IIIB NSCLC. The induction chemotherapy consisted of 3 courses of cisplatin (80 mg/m2) and docetaxel (80 mg/m2); each course was given every 21 days. Thoracic radiotherapy (TRT) was given at a dose of 60 Gy using 3-D conformal planning. All patients received a total dose of 30 Gy PCI (2 Gy/fr, 5 days a week), beginning on the first day of the TRT. Then, all patients received 3 further courses of the same chemotherapy protocol. Results Six (9.7%) patients developed brain metastases during their clinical course. Only one (2%) patient developed brain metastasis as the site of first treatment failure. Median brain metastasis-free survival, overall survival, and progression free survival were 16.6, 16.7, and 13.0 months, respectively. By univariate analysis, rates of BM were significantly higher in patients younger than 60 years of age (p = 0.03). Multivariate analysis showed no significant difference in BM-free survival according to gender, age, histology, and initial T- and N-stage. Conclusion The current finding of almost equal bone metastasis free survival and overall survival in patients with LA-NSCLC in RPA group 1 suggests a longer survival for patients who receive PCI, and thereby have a reduced risk of BM.

A rare case of primary appendiceal mucinous adenocarcinoma is reported. The presenting signs and symptoms were suggestive of acute appendicitis. An appendectomy was performed resulting in a histological diagnosis of grade 2 mucinous adenocarcinoma of the appendix. The patient was referred to our clinic where he underwent a complementary right hemicolectomy with lymph node dissection. Two of the 17 resected lymph nodes were tumor positive but there was no residual tumor in the hemicolectomy specimen. The patient was staged as T4N1M0 and adjuvant multimodality treatment was planned because he was considered at high risk for local-regional recurrence and distant metastasis. Three cycles of capecitabine 1250 mg/m2 on days 1–14 and oxaliplatin 130 mg/m2 on day 1, every 21 days (CAPOX) were administered, then a total dose of 50.4 Gy external-beam radiation therapy was deliveredtothe primarytumor region and 45 Gy to the lymphatics, and finally3 further cycles of the CAPOX regimen were administered. Multimodality treatment was well tolerated by the patient, who is still alive 25 months after the hemicolectomy procedure with no evidence of disease progression.

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

As a result of improved local and regional control with aggressive multimodality protocols, the brain has become one of the major sites of relapse in patients with locally advanced non-small cell lung carcinoma (LA-NSCLC). The demonstrated efficacy of prophylactic cranial irradiation (PCI) in small-cell lung carcinoma led to studies of its effectiveness in LA-NSCLC, which indicated that PCI also has a high potential to reduce the incidence or delay the occurrence of brain metastases in this patient group. This report provides an extensive review of the current evidence from nonrandomized and randomized trials regarding the use of PCI in LA-NSCLC and discusses related key issues including risk factors, patient selection criteria, timing of PCI, preferred PCI dosing scheme, toxicity profile and potential novel PCI techniques.

A subgroup of liver metastases, especially those emanating from colorectal carcinoma, may be cured. Surgical excision is accepted as the mainstay of treatment for these malignancies; unfortunately, however, the majority of patients presents with advanced unresectable hepatic involvement and have no standard treatment option available. Radiation therapy (RT) has not played a significant role in managing liver metastases, because the liver has little tolerance to radiation. In patients with good hepatic function, however, very-high-dose RT may be used safely and effectively if a small volume of the liver (25%) is irradiated. In particular, RT, and especially three-dimensional conformal RT (3D-CRT), may be used to manage medically unfit patients or those with an unresectable metastatic liver lesion. This review discusses existing literature on use of various types of RT, including whole-liver irradiation, partial hepatic irradiation with 3D-CRT, and hypofractionated high-dose irradiation with stereotactic body RT, and future directions for this treatment modality.

Cancer cachexia is a syndrome characterized with progressive weight loss and abnormal wasting of fat and muscle tissue, and affects 40 to 85% of all terminally ill patients, accounting more than 20% of all cancer deaths. Current treatment for cancer cachexia principally depends on its prevention rather than reversing the present disease state, and the clinical results are far from being satisfactory. Although the exact mechanism and predisposing factors have yet to be clarified in detail, our growing knowledge about the pathophysiology and biochemical changes considering this life threatening condition should help in development of future therapeutic strategies. In the present paper, the current preclinical and clinical features considering the pathophysiology and treatment of cancer related cachexia are reviewed.

Objective: To evaluate the efficacy of octreotide in the treatment of chemoradiotherapy (CRT)-induced diarrhea (CRTID) refractory to conventional loperamide treatment in this pilot study. Methods: Forty-two rectal carcinoma (T3–4N0–2M₀) patients with grade 2 or 3 diarrhea refractory to loperamide were enrolled to receive octreotide. Eligible patients were treated with pelvic radiotherapy combined with bolus 5- fluorouracil CRT. Octreotide was administered subcutaneously, 150 µg three times daily, for 5 consecutive days. Only complete resolution of diarrhea was considered as therapeutic success. Results: Diarrhea mainly occurred in the first 4 weeks of CRT (83.3%) and completely resolved in 34 patients (80.9%) following octreotide administration. Mean time to response was 2.7 days: 27 patients (64%) responded during the first 3 days, and the remaining 7 (17%) on days 4 and 5. No significant side effect was reported. Eight patients (19.1%) with refractory diarrhea were hospitalized for additional treatment. No treatment delay was reported in complete responders, whereas an average 7.7-day delay was observed in refractory patients. Antidiarrheal treatment was administered on an outpatient basis in the response group, whereas refractory patients were hospitalized for an average of 8.8 days. Conclusion: Daily subcutaneous octreotide administration (150 µg t.i.d.) for 5 days is apparently an effective, tolerable treatment modality for concurrent CRTID refractory to loperamide.

Background In this retrospective study, we investigated potential impact of weight change according to oral glutamine supplementation (GLT) on survival in patients with stage IIIB non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy. Materials and methods Of the 142 patient evaluated retrospectively, 84 received GLT (GLT+), and 58 refused GLT intake (GLT-) and analyzed as control group. GLT was given at a daily dose of 30 g in powder form mixed with fruit juices. All patients received thoracic radiotherapy (TRT) to a total dose of 60-66 Gy (2Gy/Fx) concurrently with 2 cycles of cisplatin-based chemotherapy. Results During CRT, 76 (53.5) cases lost weight while remaining cases retained or gained weight. Weight loss in GLT- group (74.1%) was more frequent than GLT+ group (39.3%) (p Table 1 ) revealed cases in GLT+ group that retained or gained weight had the best outcome compared to the others. Bonferoni correction of two groups that retained of gained weight (p must be Table: 1620 Survival results according to glutamine supplementation (GLT) and wieght loss (WL) GLT- and KK+ GLT- and KK- GLT+ and KK+ GLT+ and KK- P-value Median OS Months) (95%CI) 15.7 (11.8-19.6) 21,7 (12.1-31.3) 13.5 (9.8-17.2) Not reached yet 1-year OS 65.1 93.3 60.6 98.0 2-year OS 12.1 44.9 3.8 58.3 Conclusion Results of this study demonstrated that GLT supplementation during CRT could prevent weight loss, yielding a better survival outcome in locally advanced NSCLC. Moreover, weight loss indicates poor prognosis irrespective of GLT use, and no long term survivors in GLT- group with weight loss suggests GLT resistance as a potentially poor prognostic factor, which warrants to be verified by further studies with larger cohorts. Disclosure All authors have declared no conflicts of interest.

Background Impact of re-staging with 18F-fluoro-deoxy-glucose positron emission tomography (PET-CT) on management decision and clinical outcomes in patients with locally-advanced pancreatic carcinoma (LAPC) initially planned to undergo concurrent chemoradiotherapy (CRT) was investigated. Materials and methods Seventy-one consecutive patients with conventionally staged LAPC were re-staged with PET-CT before CRT. Patients were categorized into non-metastatic (M0) and metastatic (M1) groups according to PET-CT findings. M0patients underwent 50.4 Gy (1.8 Gy/fr) of radiotherapy and concurrent 5-FU followed by maintenance gemcitabine. Results Re-staging PET-CT revealed conventional imaging occult distant metastases in 19 cases (26.8%). Of 52 patients with LAPC confirmed by PET-CT, additional regional lymph nodes were identified to be involved in 7 (13.4%), mandating enlargement of radiation field. Taken together, PET-CT results changed or revised initial management decision in 37.2% patients. Median follow-up times for the whole, M0 and M1 cohorts were 11.3, 14.5, and 6.2 months, respectively. Median overall, locoregional progression-free, and progression-free survivals for the same cohorts were 11.4, 7.8, and 5.1 months,16.1, 9.9, and 7.4 months, and 6.2, 3.4, and 2.5 months, respectively. Survival differences between M0 and M1 cohorts were statistically significant (p Conclusions Current results demonstrated the importance of PET-CT based re-staging of LAPC in selection of suitable patients for CRT, prevention of useless aggressive treatment in metastatic cases, and precise estimation of survival outcomes of LAPC patients following radical CRT. Disclosure All authors have declared no conflicts of interest.

Background Vitamin D is a growth factor improving bone mineralization, and regulating osteoblastic activity and longitudinal bone growth. In this study, impact of vitamin D supplementation administered prior to fractionated radiotherapy (RT) in reducing RT-induced epiphyseal injury is investigated. Materials and methods Six week old male Sprague-Dawley rats were enrolled to one of the four groups: Group 1 was assigned as control group (n = 7); Group 2 received fractionated RT alone; Group 3 received 50000 IU/kg i.m. vitamin D3 injection alone; and Group 4 received 50000 IU/kg i.m. vitamin D3 injection prior to fractionated RT. Fractionated RT in the irradiated groups was delivered to distal femur and proximal tibia in the left legs of each rats to a total dose of 24 Gy in 3 fractions with the contralateral right leg as the non-irradiated control. Vitamin D3 injection in Group 3 was performed on the day before the RT. Bone growth was calculated according to the lengths of femur, tibia and total leg measured on the radiographs taken at the time and 6 weeks after the delivery of RT. Results RT resulted in a mean percent overall limb growth loss of 56.2 ± 6.7 and a mean percent overall limb discrepancy of 12.7 ± 1.3. Administration of 50000 IU/kg i.m. vitamin D3 before RT reduced the mean percent overall limb growth loss and the mean percent overall limb discrepancy to 28.5 ± 5.6 and 4.4 ± 3.3, respectively. These values were significantly different compared with the groups receiving irradiation alone (P = 0.001 for each). Conclusion These results demonstrates the potential for vitamin D3 administered before fractionated RT to significantly reduce the RT-induced epiphyseal injury. Disclosure All authors have declared no conflicts of interest.

Background Chromosomal rearrangements in the receptor tyrosine kinase (RTK) ROS1 define a new molecular subset of NSCLC. ALK inhibitors can inhibit ROS1 kinase activity in cell lines. We examined the efficacy and safety of crizotinib, a small molecule inhibitor of two other RTKs, MET and ALK, in patients with advanced, ROS1-rearranged NSCLC. Methods Patients with advanced NSCLC harboring ROS1 rearrangement, as determined using a break-apart FISH assay, were recruited into an expansion cohort of the original phase 1 study of crizotinib. Patients were treated with crizotinib at the standard oral dose of 250 mg BID. The objective response rate (ORR) was determined based on RECIST v1.0. The disease control rate (DCR; stable disease [SD] + partial response [PR] + complete response [CR]) was evaluated at weeks 8 and 16. Results At the time of data cut-off on April 19, 2012, 15 patients with ROS1 NSCLC had received crizotinib and 14 were evaluable for response. The median age was 54 years (range 31–72). Fourteen patients were never-smokers and all had adenocarcinoma histology. All patients were confirmed negative for ALK rearrangement. The median number of prior treatments was 1 (range 0–6). The first ROS1 patient received crizotinib on October 19, 2010. To date, the ORR is 57% (8/14; 95% CI 28.9–82.3), with 7 PR and 1 CR. There were 4 SD, one of which was unconfirmed as PR at the time of data cut-off. The DCR at 8 weeks was 79% (11/14). Median duration of treatment was 25.7 weeks (range 0.1 + to 65.3 + ), and 12 patients continue on study. The pharmacokinetics, antitumor activity and safety profile of crizotinib in this group of patients were similar to those observed in patients with ALK-positive NSCLC. Conclusions Crizotinib is associated with clinically significant antitumor activity in patients with ROS1 NSCLC. Similar to ALK, ROS1 rearrangement defines another unique molecular subset of NSCLC patients for whom crizotinib therapy may be highly effective. Importantly, this study represents the first clinical investigation of ROS1 as a driver mutation and therapeutic target in cancer. Disclosure S.I. Ou: Advisory role: Pfizer, Genentech. Compensated Honoraria: Pfizer, Genentech, Lilly. Myself Research funding: Pfizer. Myself (institution). D.R. Camidge: Advisory role: Pfizer. Myself. Honoraria: Pfizer. Myself. L. Tye: Employment: Pfizer. Clinician. Myself. Stock Ownership; Pfizer. Myself. K. Wilner: Emplyement: Pfizer. Senior Director. Myself. Compensated. Stock ownership: Pfizer. Myself. M. Varella-Garcia: Honoraria: Abbott Molecular. Myself. funding for the trial provided by NIH - yes. A.T. Shaw: Advisory role: Pfizer, Ariad, Chugai, Novartis, Daiichi-sankyo. Myself. Compensated Research funding: Astra Zeneca, Novartis. Myself. All other authors have declared no conflicts of interest.

Background Timing and patterns of disease progression in patients with unresectable locally-advanced pancreas carcinoma (LAPC) treated with definitive concurrent radiochemotherapy (C-RCT) was analyzed. Materials and method Fifty-two patients with histologic proof of LAPC underwent 50.4 Gy (1.8 Gy per fraction) of C-RCT with 5-FU followed by maintenance gemcitabine. Disease was considered to be unresectable if contrast-enhanced CT or staging laparoscopy/laparotomy revealed a low likelihood of complete resection and/or any of the following: involvement of superior mesenteric artery/cealiac trunk, encasement of 180 degrees or more of the circumference of superior mesenteric/portal vein, and/or evidence of narrowing of or thrombus within the superior mesenteric/portal vein. Elective nodal irradiation was not adopted. Primary aim was to assess timing and patterns of disease progression. Results Treatment was well tolerated and all patients were able to receive intended C-RCT regimen. At median 17.4 months of follow-up 38 (73.1%) were dead. Median, 1- and 2-year overall- and progression-free survival estimates were 16.1 months, 61.2% and 22.6%, and 7.4 months, 27% and 12.3% respectively. Analysis for timing of disease progression revealed that 7 (13.5%), 15 (28.8%), 20 (38.5%), and 22 (42.3%) patients experienced disease progression at 3, 4, 5, and 6 months, respectively, since initiation of R-RCT. Interestingly, although there were no isolated local or regional failures during this early follow-up period, all failures were presented as distant metastases with/without local/regional disease progression. Conclusion Results of this study demonstrated that, despite aggressive staging and treatment strategies, early distant disease progression are common source of treatment failures in unresectable LAPC. Present findings impact the urgent need for more efficacious chemotherapeutic agents for control of distant metastatatic tumor deposits and better treatment strategies, such as induction chemotherapy followed by C-RCT, to eliminate early treatment failures and unnecessary and futile C-RCT in metastatic disease state. Disclosure All authors have declared no conflicts of interest.