Trends in the treatment of human papillomavirus-associated oropharyngeal carcinoma in Slovakia.

The optimal treatment of oropharyngeal cancer (OPC) associated with human papillomavirus (HPV) is currently a subject of clinical research. This questionnaire study investigated current trends in the treatment of HPV-associated (HPV+) OPC in Slovakia with the incorporation of deintensification of oncological treatment into routine clinical practice outside of clinical trials. The Slovak Cooperative Head and Neck Cancer Group (SCHNCG) developed a questionnaire aimed at identifying trends in the oncological treatment of HPV+ OPC intended for all radiation oncology (RO) facilities in Slovakia. Specialists in the field of RO responded to general questions about the character of their individual institutions as well as to 4 theoretical clinical scenarios (case reports) regarding the treatment of HPV+ OPC, focusing primarily on the applied dose of radiotherapy (RT), the extent of target volumes, and the type of concurrent chemotherapy (CHT). The questionnaire study involved 35 RO specialists from 14 institutions in Slovakia. Regarding primary chemoradiotherapy (CRT) in T1N1M0 HPV+ OPC, 16 respondents (45.7%) would consider de-escalation of the RT dose to <70 Gy. In the case of postoperative RT in pT1pN1M0 HPV+ OPC with negative resection margins (R0) and absent extracapsular extension (ECE), 4 physicians (11.4%) would consider de-escalation of the RT dose to <60 Gy in the tumor bed area, while the majority of the treating specialists (n=19, 54.3%) would omit concurrent CHT. In the case of primary RT in elderly patient with T2N1M0 HPV+ OPC, the same number of physicians (n=16, 45.7%) would consider de-escalation of the RT dose to <70 Gy, and 14 respondents (40.0%) would completely omit CHT. In a high-risk patient with T2N3M0 HPV+ OPC with a complete response after 3 cycles of induction chemotherapy (iCHT), none of the respondents would indicate a reduction in the RT dose to the area of the original tumor and lymphadenopathy to <60 Gy. The doses and extent of irradiated volumes in the treatment of HPV+ OPC in Slovakia vary among different institutions. The tendency to de-escalate RT doses and reduce doses of concurrent systemic therapy in Slovakia is high and there was also an observed trend to reduce the extent of radiation treatment fields.

Chemotherapy and radiotherapy in locally advanced head and neck cancer: an individual patient data network meta-analysis.

BACKGROUND: Randomised, controlled trials and meta-analyses have shown the survival benefit of concomitant chemoradiotherapy or hyperfractionated radiotherapy in the treatment of locally advanced head and neck cancer. However, the relative efficacy of these treatments is unknown. We aimed to determine whether one treatment was superior to the other. METHODS: We did a frequentist network meta-analysis based on individual patient data of meta-analyses evaluating the role of chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC]) and of altered fractionation radiotherapy (Meta-Analysis of Radiotherapy in Carcinomas of Head and Neck [MARCH]). Randomised, controlled trials that enrolled patients with non-metastatic head and neck squamous cell cancer between Jan 1, 1980, and Dec 31, 2016, were included. We used a two-step random-effects approach, and the log-rank test, stratified by trial to compare treatments, with locoregional therapy as the reference. Overall survival was the primary endpoint. The global Cochran Q statistic was used to assess homogeneity and consistency and P score to rank treatments (higher scores indicate more effective therapies). FINDINGS: 115 randomised, controlled trials, which enrolled patients between Jan 1, 1980, and April 30, 2012, yielded 154 comparisons (28 978 patients with 19 253 deaths and 20 579 progression events). Treatments were grouped into 16 modalities, for which 35 types of direct comparisons were available. Median follow-up based on all trials was 6·6 years (IQR 5·0-9·4). Hyperfractionated radiotherapy with concomitant chemotherapy (HFCRT) was ranked as the best treatment for overall survival (P score 97%; hazard ratio 0·63 [95% CI 0·51-0·77] compared with locoregional therapy). The hazard ratio of HFCRT compared with locoregional therapy with concomitant chemoradiotherapy with platinum-based chemotherapy (CLRTP) was 0·82 (95% CI 0·66-1·01) for overall survival. The superiority of HFCRT was robust to sensitivity analyses. Three other modalities of treatment had a better P score, but not a significantly better HR, for overall survival than CLRTP (P score 78%): induction chemotherapy with taxane, cisplatin, and fluorouracil followed by locoregional therapy (ICTaxPF-LRT; 89%), accelerated radiotherapy with concomitant chemotherapy (82%), and ICTaxPF followed by CLRT (80%). INTERPRETATION: The results of this network meta-analysis suggest that further intensifying chemoradiotherapy, using HFCRT or ICTaxPF-CLRT, could improve outcomes over chemoradiotherapy for the treatment of locally advanced head and neck cancer. FUNDINGS: French Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC.

Molecular profiling and characteristics of non-small-cell lung cancer patients in Georgia.

Aims: In patients with advanced non-small-cell lung cancer, the correlation between histopathology, smoking status, driver oncogene mutations and PD-L1 overexpression were investigated. Patients and methods: A total of 202 patients were identified. Research was done in Georgia. Results: EGFR mutations were detected in 6% of the tested cases (12/187) and five out of 12 EGFR+ cases had histology consistent with squamous cell carcinoma. No statistically significant correlation was observed between PD-L1 expression, smoking status and clinicopathological characteristics. However, the correlation between smoking status and histology was statistically significant (p = 0.0264), as never-smokers had a higher incidence of adenocarcinoma histology. Conclusion: The study showed a small percentage of EGFR mutations associated with adenocarcinoma histology and revealed a solid existence of this mutation in squamous cell carcinoma histology. A higher incidence of adenocarcinoma histology was observed in never-smokers.

Towards continuous and real-time attention monitoring at work: reaction time versus brain response.

Continuous and objective measurement of the user attention state still represents a major challenge in the ergonomics research. Recently available wearable electroencephalography (EEG) opens new opportunities for objective and continuous evaluation of operators' attention, which may provide a new paradigm in ergonomics. In this study, wearable EEG was recorded during simulated assembly operation, with the aim to analyse P300 event-related potential component, which provides reliable information on attention processing. In parallel, reaction times (RTs) were recorded and the correlation between these two attention-related modalities was investigated. Negative correlation between P300 amplitudes and RTs has been observed on the group level (p < .001). However, on the individual level, the obtained correlations were not consistent. As a result, we propose the P300 amplitude for accurate attention monitoring in ergonomics research. On the other hand, no significant correlation between RTs and P300 latency was found on group, neither on individual level. Practitioner Summary: Ergonomic studies of assembly operations mainly investigated physical aspects, while mental states of the assemblers were not sufficiently addressed. Presented study aims at attention tracking, using realistic workplace replica. It is shown that drops in attention could be successfully traced only by direct brainwave observation, using wireless electroencephalographic measurements.

Effect of radiotherapy delay in overall treatment time on local control and survival in head and neck cancer: Review of the literature.

Treatment delays in completing radiotherapy (RT) for many neoplasms are a major problem affecting treatment outcome, as increasingly shown in the literature. Overall treatment time (OTT) could be a critical predictor of local tumor control and/or survival. In an attempt to establish a protocol for managing delays during RT, especially for heavily overloaded units, we have extensively reviewed the available literature on head and neck cancer. We confirmed a large deleterious effect of prolonged OTT on both local control and survival of these patients.

Computer simulation of cervical tissue response to a hydraulic dilator device.

BACKGROUND: Classical mechanical dilators for cervical dilation are associated with various complications, such as uterine perforation, cervical laceration, infections and intraperitoneal hemorrhage. A new medical device called continuous controllable balloon dilator (CCBD) was constructed to make a significant reduction in all of the side effects of traditional mechanical dilation. METHOD: In this study we investigated numerically the cervical canal tissue response for Hegar and CCBD using our poroelastic finite element model and in-house software development. Boundary conditions for pressure loading on the tissue for both dilators in vivo were measured experimentally. Material properties of the cervical tissue were fitted with experimental in vivo data of pressure and fluid volume or balloon size. RESULTS: Obtained results for effective stresses inside the cervical tissue clearly showed higher stresses for Hegar dilator during dilation in comparison with our CCBD. CONCLUSION: This study opens a new avenue for the implementation of CCBD device instead of mechanical dilators to prevent cervical injury during cervical dilation.

Consolidation Systemic Therapy in Locally Advanced, Inoperable Nonsmall Cell Lung Cancer-How to Identify Patients Which Can Benefit from It?

BACKGROUND: Consolidation systemic therapy (ST) given after concurrent radiotherapy (RT) and ST (RT-ST) is frequently practiced in locally advanced inoperable nonsmall cell lung cancer (NSCLC). Little is known, however, about the fate of patients achieving different responses after concurrent phases of the treatment. METHODS: we searched the English-language literature to identify full-length articles on phase II and Phase III clinical studies employing consolidation ST after initial concurrent RT-ST. We sought information about response evaluation after the concurrent phase and the outcome of these patient subgroups, the patterns of failure per response achieved after the concurrent phase as well as the outcome of these subgroups after the consolidation phase. RESULTS: Eighty-seven articles have been initially identified, of which 20 studies were excluded for various reasons, leaving, therefore, a total of 67 studies for our analysis. Response evaluation after the concurrent phase was performed in 36 (54%) studies but in only 14 (21%) response data were provided, while in 34 (51%) studies patients underwent a consolidation phase regardless of the response. No study provided any outcome (survivals, patterns of failure) as per response achieved after the concurrent phase. CONCLUSIONS: Information regarding the outcome of subgroups of patients achieving different responses after the concurrent phase and before the administration of the consolidation phase is still lacking. This may negatively affect the decision-making process as it remains unknown which patients may preferentially benefit from the consolidation of ST.

Human Papillomavirus-Related Non-Metastatic Oropharyngeal Carcinoma: Current Local Treatment Options and Future Perspectives.

Over the last two decades, human papillomavirus (HPV) has caused a new pandemic of cancer in many urban areas across the world. The new entity, HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), has been at the center of scientific attention ever since, not only due to its distinct biological behavior, but also because of its significantly better prognosis than observed in its HPV-negative counterpart. The very good treatment outcomes of the disease after primary therapy (minimally-invasive surgery, radiation therapy with or without chemotherapy) resulted in the creation of a separate staging system, reflecting this excellent prognosis. A substantial proportion of newly diagnosed HPV-driven OPSCC is diagnosed in stage I or II, where long-term survival is observed worldwide. Deintensification of the primary therapeutic methods, aiming at a reduction of long-term toxicity in survivors, has emerged, and the quality of life of the patient after treatment has become a key-point in many clinical trials. Current treatment recommendations for the treatment of HPV-driven OPSCC do not differ significantly from HPV-negative OPSCC; however, the results of randomized trials are eagerly awaited and deemed necessary, in order to include deintensification into standard clinical practice.

Clinical prognostic factors in patients with locally advanced (stage III) nonsmall cell lung cancer treated with hyperfractionated radiation therapy with and without concurrent chemotherapy: single-Institution Experience in 600 Patients.

BACKGROUND: Influence of potential clinical prognostic factors on overall survival (OS), local progression-free survival (PFS), and distant metastasis-free survival (MFS) in patients with locally advanced nonsmall cell lung cancer treated with hyperfractionated radiation therapy (HFX RT) with or without concurrent chemotherapy was investigated. METHODS: Three phase 3 and 2 phase 2 studies have been designed and executed with a total of 600 patients. HFX RT alone was given in 127 and HFX RT-chemotherapy was given in 473 patients. HFX RT doses were either 64.8 grays (Gy) or 69.6 Gy using 1.2 Gy twice daily, or 67.6 Gy using 1.3 Gy twice daily. Chemotherapy consisted of concurrent carboplatin and etoposide in 409 patients and concurrent carboplatin and paclitaxel in 64 patients. Sex, age, Karnofsky performance score (KPS), weight loss (>5%), stage, histology, interfraction interval, and treatment (the addition of concurrent chemotherapy) were investigated as potential prognostic factors. RESULTS: The median OS, median local PFS, and median distant MFS times were 19, 21, and 23 months, respectively. Five-year OS, local PFS, and distant MFS rates were 19%, 29%, and 35%, respectively. Univariate and multivariate analysis showed that only age did not influence OS and local PFS, whereas female sex, lower KPS, less pronounced weight loss, lower stage, squamous histology, shorter interfraction interval, and treatment independently predicted better OS and local PFS. Only age and treatment did not influence distant MFS, whereas histology was of borderline significance. CONCLUSIONS: This study identified independent prognosticators of treatment outcome. These results may have implications for future studies in this disease.

Real-World Treatment Patterns of Lung Cancer in a Resource-Restricted Country: the Experience of Georgia.

Lung cancer (LC) is the most common malignancy responsible for 1.8 million of deaths worldwide. Lung and bronchus cancer represents 13% (n = 1217) of all new cancer cases in Georgia. In 2018, in Georgian males lung cancer age-standardized incidence rate was 35.7/per 100 000, less compared to regional countries as Turkey (70.6), Russia (48.2), Ukraine (41.7), and Armenia (58.5), but higher than in neighbor Azerbaijan (25.5). Incidence is higher compared to central and eastern Europe (27.3) and near similar to North America (34.5). Georgia is an Eastern European, middleincome country with 3.7 million residents and one of the highest numbers of active smokers in the European Region. The Georgian health care system is divided into a public and a private sector, with coverage of nearly 100% of the population. There is a national healthcare system as well as private insurance and all patients, irrespective of insurance (private or governmental) can choose the hospital for treatment by themselves all over the country. The Basic Package of the Universal Health Care Program includes the treatment of oncologic patients, specifically surgery, chemotherapy, hormone therapy and radiotherapy and investigations and medications related to these procedures. The program covers all types of laboratory and instrumental investigations related to planned treatment. Georgia lacks an LC screening program for smokers and partially because of this, the majority of patients with lung cancer present at an advanced stage. The National Centre for the Disease Control (NCDC) showed that almost 90% of LC patients in the country present with advanced stages (III-IV) with 60% of patients having stage IV disease at diagnosis . Lung cancer is generally diagnosed at an advanced stage. For non-small cell lung cancer (NSCLC), the proportion with metastatic disease (TNM stage IV) ranged from 46.8% to 61.2% in developed countries. In recent years, there have been several publications addressing specifics of LC worldwide, but none concerning Georgia. In light of the rapidly changing landscape in the diagnosis, staging, and treatment of LC, we thought to define the state of practice in Georgia by convening specialists who treat LC across 13 institutions in our country with the goal to describe differences in access and approaches to LC.

Biology of NSCLC: Interplay between Cancer Cells, Radiation and Tumor Immune Microenvironment.

The overall prognosis and survival of non-small cell lung cancer (NSCLC) patients remain poor. The immune system plays an integral role in driving tumor control, tumor progression, and overall survival of NSCLC patients. While the tumor cells possess many ways to escape the immune system, conventional radiotherapy (RT) approaches, which are directly cytotoxic to tumors, can further add additional immune suppression to the tumor microenvironment by destroying many of the lymphocytes that circulate within the irradiated tumor environment. Thus, the current immunogenic balance, determined by the tumor- and radiation-inhibitory effects is significantly shifted towards immunosuppression, leading to poor clinical outcomes. However, newer emerging evidence suggests that tumor immunosuppression is an "elastic process" that can be manipulated and converted back into an immunostimulant environment that can actually improve patient outcome. In this review we will discuss the natural immunosuppressive effects of NSCLC cells and conventional RT approaches, and then shift the focus on immunomodulation through novel, emerging immuno- and RT approaches that promise to generate immunostimulatory effects to enhance tumor control and patient outcome. We further describe some of the mechanisms by which these newer approaches are thought to be working and set the stage for future trials and additional preclinical work.

Radiation therapy for early stage (I/II) non-small cell lung cancer.

For patients with early (stage I/II) non-small cell lung cancer (NSCLC) surgery is considered as the standard treatment of choice, although recent data on additional chemotherapy (CHT) showed that it may be beneficial in this setting. There is, however, a subset of patients that never undergo surgery. These patients are considered technically operable, but medically inoperable, due to existing comorbidities. In addition, frequently elderly patients with early NSCLC are denied surgery due to expected peri- and/or postoperative complications. Finally, in recent years there has been an increase in the incidence of patients refusing surgery. For all these patients, radiation therapy (RT) was traditionally considered as the standard treatment option. Data accumulated over the last 5 decades showed that RT alone can produce median survival times of up to > 30 months and 5-year survival of up to 30%. When cancer-unrelated deaths were taken into account, cause-specific survival rates were usually higher for some 10-15%. Accumulated experience seems to suggest that doses of at least 65 Gy with standard fractionation or its equivalent when altered fractionation is used are necessary for control of the disease. Smaller tumors seem to have favorable prognosis, while the issue of elective nodal RT continues to be controversial. Patterns of failure have clearly identified local failure as the predominant one. Although a number of potential pretreatment patient- and tumor-related prognostic factors have been examined, none has been shown to clearly influenced survival. Toxicity was usually low.

Radiochemotherapy in extensive disease small cell lung cancer ED-SCLC.

Patients with extensive disease small cell lung cancer (ED-SCLC) represent approximately one-third of all SCLC patients. For these patients, chemotherapy (CHT) is the standard treatment of choice. With CHT given alone, however, there is not a high risk of distant progression, but also progression within the thorax and brain frequently occurs, even in patients achieving a response to CHT. To improve poor figures obtained with CHT alone and address important issue of intrathoracic tumor control and it relationship to overall survival, thoracic radiation therapy (TRT) was introduced with a curative intent in a prospective randomized trial by Jeremic et al (1988-1993). In that trial CHT alone was compared with CHT followed by TRT, and in both groups by a prophylactic cranial irradiation. This trial showed that TRT can offer an improvement on local control that leads to an improvement in overall survival. Toxicity was acceptable, while multivariate analysis identified number of metastasis as an independent prognosticator of outcome. Based on the data of this trial, researchers in the USA and Europe will undergo two prospective trials addressing the issue of TRT in ED-SCLC.

Stereotactic body radiation therapy for early non-small cell lung cancer.

For patients with early stage non-small cell lung cancer (NSCLC) unsuitable for resection local high-dose radiotherapy is the treatment of choice. In modern series even with escalated conformal radiotherapy local control rates of about 55% remain disappointing. Within the last years, stereotactic radiotherapy has been shown an effective treatment approach for early stage malignant lung tumors, combining the accurate focal dose delivery by stereotactic techniques with the biological advantages of dose escalated hypofractionated radiotherapy. Typical treatment regimens include three to five fractions over 1-2 weeks or 1 single fraction as radiosurgery. With adequate staging procedures including FDG-PET-CT scan and a low probability of subclinical involvement of unsuspicious locoregional lymph nodes, the concept is to irradiate the primary T1/2 tumor alone. Recent data report local control rates of up to 90%, with favorable results especially for patients in good general condition. Less than 10% of all patients develop isolated tumor recurrences in regional lymph nodes. Three-year survival is significantly improved to more than 80% when biological effective doses of more than 100 Gy are applied to patients in good conditions. Systemic tumor recurrence still is a major problem, making an additional systemic chemotherapy interesting for selected patients after hSRT, such as those younger than 75 years.

Radiation-induced lung toxicity - cellular and molecular mechanisms of pathogenesis, management, and literature review.

Lung, breast, and esophageal cancer represent three common malignancies with high incidence and mortality worldwide. The management of these tumors critically relies on radiotherapy as a major part of multi-modality care, and treatment-related toxicities, such as radiation-induced pneumonitis and/or lung fibrosis, are important dose limiting factors with direct impact on patient outcomes and quality of life. In this review, we summarize the current understanding of radiation-induced pneumonitis and pulmonary fibrosis, present predictive factors as well as recent diagnostic and therapeutic advances. Novel candidates for molecularly targeted approaches to prevent and/or treat radiation-induced pneumonitis and pulmonary fibrosis are discussed.

Use of PET and PET/CT for radiation therapy planning: IAEA expert report 2006-2007.

Positron Emission Tomography (PET) is a significant advance in cancer imaging with great potential for optimizing radiation therapy (RT) treatment planning and thereby improving outcomes for patients. The use of PET and PET/CT in RT planning was reviewed by an international panel. The International Atomic Energy Agency (IAEA) organized two synchronized and overlapping consultants' meetings with experts from different regions of the world in Vienna in July 2006. Nine experts and three IAEA staff evaluated the available data on the use of PET in RT planning, and considered practical methods for integrating it into routine practice. For RT planning, (18)F fluorodeoxyglucose (FDG) was the most valuable pharmaceutical. Numerous studies supported the routine use of FDG-PET for RT target volume determination in non-small cell lung cancer (NSCLC). There was also evidence for utility of PET in head and neck cancers, lymphoma and in esophageal cancers, with promising preliminary data in many other cancers. The best available approach employs integrated PET/CT images, acquired on a dual scanner in the radiotherapy treatment position after administration of tracer according to a standardized protocol, with careful optimization of images within the RT planning system and carefully considered rules for contouring tumor volumes. PET scans that are not recent or were acquired without proper patient positioning should be repeated for RT planning. PET will play an increasing valuable role in RT planning for a wide range of cancers. When requesting PET scans, physicians should be aware of their potential role in RT planning.

Time-synchronized immune-guided SBRT partial bulky tumor irradiation targeting hypoxic segment while sparing the peritumoral immune microenvironment.

BACKGROUND: A novel unconventional SBRT-based PArtial Tumor irradiation targeting HYpoxic clonogenic cells (SBRT-PATHY) for induction of the tumoricidal bystander (BE) and abscopal effects (AE) was developed by translating our preclinical findings to a clinic in 2016. In order to further improve BE/AE response rate, SBRT-PATHY was upgraded in 2018 by the sparing of peritumoral immune microenvironment as a new OAR, defined by its own dose-constraints. Considering the anti-tumor immune response homeostatic fluctuation, which is cyclically suppressed and incited ("switched off and on"), we synchronized SBRT-PATHY with its most excitable phase, in order to overcome tumor tolerance locally and systemically. The aim of this study, therefore, was to report on the initial results of our latest innovation aimed to further improve BE/AE response rate by testing the effectiveness of the time-synchronized immune-guided SBRT-PATHY. MATERIALS AND METHODS: In order to serially map the homeostatic anti-tumor immune response-fluctuations, High Sensitive C-Reactive Protein (HS-CRP), Lactate Dehydrogenase (LDH) and Lymphocyte/Monocyte Ratio (LMR) were analyzed using high-order polynomial trend analysis as surrogate of immune system response. After the biomarker data analysis detected the immune fluctuations and related idiosyncratic immune cycle periodicity, we determined the "most favourable" and "least favourable" treatment time-positions in the immune cycle. In order to evaluate the impact of an idiosyncratic immune cycle on treatment outcomes, our first consecutive four patients were treated on the "most favourable" while the remaining four on the "least favourable" day. RESULTS: The median follow-up was 11.8 months. The biomarker data analysis showed periodic immune response fluctuations of regular frequency. The "right" synchronization of SBRT-PATHY with the "most favorable day" of anti-tumor immune response was accompanied with improved clinical outcomes in terms of BE/AE-response rate. CONCLUSION: We believe the right synchronization of radiotherapy with the homeostatically oscillating immune response may improve the probability of inducing BE/AE. Present study has been retrospectively registered on 18th of October 2019 by the ethic committee for Austrian region "Kärnten "in Klagenfurt (AUT), under study number A 37/19.

Mono-institutional phase 2 study of innovative Stereotactic Body RadioTherapy targeting PArtial Tumor HYpoxic (SBRT-PATHY) clonogenic cells in unresectable bulky non-small cell lung cancer: profound non-targeted effects by sparing peri-tumoral immune microenvironment.

BACKGROUND: Radiotherapy-induced lymphopenia may be limiting the success of therapy and could also negatively affect the ability of immune system in mediating the bystander (BE) and abscopal effects (AE). A novel SBRT-based PArtial Tumor irradiation of HYpoxic clonogenic cells (SBRT-PATHY) for induction of the tumoricidal BE and AE by sparing the peritumoral immune microenvironment and regional circulating lymphocytes has been developed to enhance the radiotherapy therapeutic ratio of advanced lung cancer. The aim of this retrospective review of prospectively collected mono-institutional phase 2 study was to compare the outcomes between unconventional SBRT-PATHY and standard of care in unresectable stage IIIB/IV bulky NSCLC. MATERIALS AND METHODS: Sixty patients considered inoperable or unsuitable for radical radio-chemotherapy were enrolled and treated using the following 3 regimens: SBRT-PATHY (group I, n = 20 patients), recommended standard of care chemotherapy (group II, n = 20 patients), and institutional conventional palliative radiotherapy (group III, n = 20 patients). RESULTS: Median follow-up was 13 months. The 1-year overall survival was 75, 60, and 20% in groups 1, 2 and 3, respectively (p = 0.099). The 1-year cancer specific survival was 90, 60, and 20% in groups 1, 2, and 3, respectively (p = 0.049). Bulky tumor control rate was 95% for SBRT-PATHY compared with 20% in the other two groups. BE and AE were seen by SBRT-PATHY in 95 and 45% of patients, respectively. Multi-variate analysis for cancer specific survival was significant for treatment effect with SBRT-PATHY (p < 0.001) independent of age, sex, performance status, histology, stage, treated bulky site and tumor diameter. SBRT-PATHY resulted in lower toxicity (p = 0.026), and improved symptom control (p = 0.018) when compared to other two treatment options. CONCLUSION: SBRT-PATHY improved treatment outcomes in unresectable NSCLC and should be investigated in larger trials. Present study has been retrospectively registered on 8th of August 2019 by the ethic committee for Austrian region "Kärnten "in Klagenfurt (AUT), under study number A 31/19.

Role of thoracic consolidation radiation in extensive stage small cell lung cancer: A systematic review and meta-analysis of randomised controlled trials.

Extensive stage small cell lung cancer (ES-SCLC) carries a poor prognosis, and the thoracic progression is common. Consolidation radiation to thoracic disease (cRT) could improve progression-free survival (PFS) and overall survival (OS). We conducted an electronic search of PubMed and Embase with no language, year or publication status restrictions and evaluated randomised controlled trials (RCTs) addressing the role of cRT in ES-SCLC. Preferred Reporting of Systematic Reviews and Meta-Analyses guidelines for systematic review and Cochrane methodology for meta-analysis were followed. Effect estimates (hazard ratios [HRs] and confidence intervals [CIs]) and risk ratios were extracted, with a fixed/random-effects model created to estimate treatment effects. I2 statistics and heterogeneity statistics were performed. Comprehensive and systematic search identified 1107 records, after removal of duplicate records screened 922 records, assessed 31 full-text articles for eligibility and 3 RCTs with a total of 690 patients were included. Pooled analysis showed cRT significant improved PFS (p < 0.0001) with HR 0.72 (95% CI: 0.61-0.83, I2-0%). In addition, cRT significantly (p < 0.001) reduced the risk of thoracic progression as the first site of progression with a relative risk of 0.52 (95% CI: 0.44-0.61, I2-0%). OS analysis showed no significant (p = 0.36) benefit with HR of 0.88 (95% CI 0.66-1.18, I2-52%) with cRT. Pooled meta-analysis of 3 randomised controlled studies shows consolidation thoracic radiotherapy (RT) offers significant improvement in PFS and reduction in thoracic failures. Further research on subclassification of ES-SCLC (limited vs extensive metastasis), optimise strategy for RT integration (sequential vs concurrent) and optimal RT dose is needed to identify the subset of ES-SCLC likely to have significant OS benefit.