American Society of Clinical Oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) Mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy. Accelerated Partial Breast Irradiation: Executive summary for the update of an ASTRO Evidence-Based Consensus Statement. Stereotactic body radiation therapy for early-stage non-small cell lung cancer: Executive Summary of an ASTRO Evidence-Based Guideline. Impact of Intensity-Modulated Radiation Therapy Technique for Locally Advanced Non-Small-Cell Lung Cancer: A Secondary Analysis of the NRG Oncology RTOG 0617 Randomized Clinical Trial. Phase I study of a decision aid for patients with locally advanced non-small-cell lung cancer. Stereotactic body radiation therapy versus conventional radiation therapy in patients with early stage non-small cell lung cancer: An updated retrospective study on local failure and survival rates Hypofractionated Radiation Therapy for Localized Prostate Cancer: Executive Summary of an ASTRO, ASCO, and AUA Evidence-Based Guideline. Stereotactic body radiotherapy versus surgery for medically operable Stage I non-small-cell lung cancer: a Markov model-based decision analysis. The impact of tumor size on outcomes after stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer. Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO). Dose-limiting toxicity after hypofractionated dose-escalated radiotherapy in non-small-cell lung cancer. The outcome of combined-modality therapy for stage III non-small-cell lung cancer in the elderly. A randomized clinical trial comparing radiation therapy v radiation therapy plus cis-dichlorodiammine platinum (II) in the treatment of locally advanced non-small cell lung cancer. Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial. Treatment of stage III non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Phase 1 study of dose escalation in hypofractionated proton beam therapy for non-small cell lung cancer. Long-term treatment sequelae after external beam irradiation with or without hormonal manipulation for adenocarcinoma of the prostate: analysis of radiation therapy oncology group studies 85-31, 86-10, and 92-02. Hyperfractionated radiation therapy with or without concurrent low-dose daily carboplatin/etoposide for stage III non-small-cell lung cancer: a randomized study. Long-term results of S-1 plus cisplatin with concurrent thoracic radiotherapy for locally advanced non-small-cell lung cancer Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02. Hypofractionated/accelerated radiotherapy with cytoprotection (HypoARC) combined with vinorelbine and liposomal doxorubicin for locally advanced non-small cell lung cancer (NSCLC). Adjuvant carboplatin and paclitaxel chemotherapy interposed with involved field radiation for advanced endometrial cancer. Neoadjuvant chemotherapy and radical surgery versus exclusive radiotherapy in locally advanced squamous cell cervical cancer: results from the Italian multicenter randomized study.
PURPOSE An American Society of Clinical Oncology ( ASCO ) provisional clinical opinion ( PCO ) offers timely clinical direction to ASCO 's membership following publication or presentation of potentially practice -changing data from major studies . This PCO addresses the clinical utility of using epidermal growth factor receptor ( EGFR ) mutation testing for patients with advanced non-small-cell lung cancer ( NSCLC ) to predict the benefit of taking a first-line EGFR tyrosine kinase inhibitor ( TKI ) . CLINICAL CONTEXT Patients with EGFR-mutated NSCLC have a significantly higher rate of partial responses to the EGFR TKIs gefitinib and erlotinib . In the United States , approximately 15 % of patients with adenocarcinoma of the lung harbor activating EGFR mutations . EGFR mutation testing is widespread at academic medical centers and in some locales in community practice . As of yet , there is no evidence of an overall survival ( OS ) benefit from selecting treatment based on performing this testing . RECENT DATA One large phase III trial ( the Iressa Pan-Asia Study [ IPASS ] trial ) , three smaller phase III r and omized controlled trials using progression-free survival as the primary end point , and one small phase III trial with OS as the primary end point , all involving first-line EGFR TKIs and chemotherapy doublets , form the basis of this PCO . PROVISIONAL CLINICAL OPINION On the basis of the results of five phase III r and omized controlled trials , patients with NSCLC who are being considered for first-line therapy with an EGFR TKI ( patients who have not previously received chemotherapy or an EGFR TKI ) should have their tumor tested for EGFR mutations to determine whether an EGFR TKI or chemotherapy is the appropriate first-line therapy . NOTE . ASCO 's provisional clinical opinions ( PCOs ) reflect expert consensus based on clinical evidence and literature available at the time they are written and are intended to assist physicians in clinical decision making and identify questions and setting s for further research . Because of the rapid flow of scientific information in oncology , new evidence may have emerged since the time a PCO was su bmi tted for publication . PCOs are not continually up date d and may not reflect the most recent evidence . PCOs can not account for individual variation among patients and can not be considered inclusive of all proper methods of care or exclusive of other treatments . It is the responsibility of the treating physician or other health care provider , relying on independent experience and knowledge of the patient , to determine the best course of treatment for the patient . Accordingly , adherence to any PCO is voluntary , with the ultimate determination regarding its application to be made by the physician in light of each patient 's individual circumstances . ASCO PCOs describe the use of procedures and therapies in clinical practice and can not be assumed to apply to the use of these interventions in the context of clinical trials . ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of ASCO 's PCOs , or for any errors or omissions PURPOSE To up date the accelerated partial breast irradiation Consensus Statement published in 2009 and provide guidance on use of intraoperative radiation therapy ( IORT ) for partial breast irradiation in early-stage breast cancer , based on published evidence complemented by expert opinion . METHODS AND MATERIAL S A systematic PubMed search using the same terms as the original Consensus Statement yielded 419 articles ; 44 articles were selected . The authors synthesized the published evidence and , through a series of conference calls and e-mails , reached consensus regarding the recommendations . RESULTS The new recommendations include lowering the age in the " suitability group " from 60 to 50 years and in the " caution ary group " to 40 years for patients who meet all other elements of suitability ( Table 1 ) . Patients with low-risk ductal carcinoma in situ , as per Radiation Therapy Oncology Group 9804 criteria , were categorized in the " suitable " group . The task force agreed to maintain the current criteria based on margin status . Recommendations for the use of IORT for breast cancer patients include : counseling patients regarding the higher risk of ipsilateral breast tumor recurrence with IORT compared with whole breast irradiation ; the need for prospect i ve monitoring of long-term local control and toxicity with low-energy radiograph IORT given limited follow-up ; and restriction of IORT to women with invasive cancer considered " suitable . " CONCLUSION These recommendations will provide up date d clinical guidance regarding use of accelerated partial breast irradiation for radiation oncologists and other specialists participating in the care of breast cancer patients PURPOSE This guideline presents evidence -based recommendations for stereotactic body radiation therapy ( SBRT ) in challenging clinical scenarios in early-stage non-small cell lung cancer ( NSCLC ) . METHODS AND MATERIAL S The American Society for Radiation Oncology convened a task force to perform a systematic literature review on 4 key questions addressing : ( 1 ) application of SBRT to operable patients ; ( 2 ) appropriate use of SBRT in tumors that are central ly located , large , multifocal , or unbiopsied ; ( 3 ) individual tailoring of SBRT in " high-risk " clinical scenarios ; and ( 4 ) SBRT as salvage therapy after recurrence . Guideline recommendations were created using a predefined consensus-building methodology supported by American Society for Radiation Oncology-approved tools for grading evidence quality and recommendation strength . RESULTS Although few r and omized trials have been completed for SBRT , strong consensus recommendations based on extensive , consistent publications were generated for several questions , including recommendations for fractionation for central tumors and surgery versus SBRT in st and ard-risk medically operable patients with early-stage NSCLC . Lower quality evidence led to conditional recommendations on use of SBRT for tumors > 5 cm , patients with prior pneumonectomy , T3 tumors with chest wall invasion , synchronous multiple primary lung cancer , and as a salvage therapy after prior radiation therapy . These areas of moderate- and low- quality evidence highlight the importance of clinical trial enrollment as well as the role of prospect i ve data registries . CONCLUSIONS SBRT has an important role to play in treating early-stage NSCLC , particularly for medically inoperable patients with limited other treatment options . Shared decision-making with patients should be performed in all cases to ensure the patient underst and s the risks related to SBRT , the side effects , and the alternative treatments available Purpose Although intensity-modulated radiation therapy ( IMRT ) is increasingly used to treat locally advanced non-small-cell lung cancer ( NSCLC ) , IMRT and three-dimensional conformal external beam radiation therapy ( 3D-CRT ) have not been compared prospect ively . This study compares 3D-CRT and IMRT outcomes for locally advanced NSCLC in a large prospect i ve clinical trial . Patients and Methods A secondary analysis was performed to compare IMRT with 3D-CRT in NRG Oncology clinical trial RTOG 0617 , in which patients received concurrent chemotherapy of carboplatin and paclitaxel with or without cetuximab , and 60- versus 74-Gy radiation doses .  Comparisons included 2-year overall survival ( OS ) , progression-free survival , local failure , distant metastasis , and selected Common Terminology Criteria for Adverse Events ( version 3 ) ≥ grade 3 toxicities . Results The median follow-up was 21.3 months . Of 482 patients , 53 % were treated with 3D-CRT and 47 % with IMRT . The IMRT group had larger planning treatment volumes ( median , 427 v 486 mL ; P = .005 ) ; a larger planning treatment volume/volume of lung ratio ( median , 0.13 v 0.15 ; P = .013 ) ; and more stage IIIB disease ( 30.3 % v 38.6 % , P = .056 ) . Two-year OS , progression-free survival , local failure , and distant metastasis-free survival were not different between IMRT and 3D-CRT . IMRT was associated with less ≥ grade 3 pneumonitis ( 7.9 % v 3.5 % , P = .039 ) and a reduced risk in adjusted analyses ( odds ratio , 0.41 ; 95 % CI , 0.171 to 0.986 ; P = .046 ) . IMRT also produced lower heart doses ( P < .05 ) , and the volume of heart receiving 40 Gy ( V40 ) was significantly associated with OS on adjusted analysis ( P < .05 ) . The lung V5 was not associated with any ≥ grade 3 toxicity , whereas the lung V20 was associated with increased ≥ grade 3 pneumonitis risk on multivariable analysis ( P = .026 ) . Conclusion IMRT was associated with lower rates of severe pneumonitis and cardiac doses in NRG Oncology clinical trial RTOG 0617 , which supports routine use of IMRT for locally advanced NSCLC PURPOSE Many patients with locally advanced non-small-cell lung cancer ( LA-NSCLC ) are eligible for combined-modality therapy ( CMT ; chemotherapy and radiotherapy ) . Although CMT offers slightly higher chances of survival than radiotherapy alone ( RT ) , it also carries a higher probability of toxicity , raising the possibility that some patients may prefer to decline CMT . We report a pilot study of a decision aid design ed for patients in this setting . PATIENTS AND METHODS The aid included a structured description of the treatment options and trade-off exercises design ed to help clarify the patient 's values for the relevant outcomes by determining the patient 's survival advantage threshold ( SAT ; the increase in survival conferred by CMT over RT that the patient deemed necessary for choosing CMT ) . Additional outcome measures included each patient 's strength of treatment preference , decisional conflict , objective underst and ing of survival information , and decisional role preference . RESULTS Twenty-seven patients met the eligibility criteria for the study . Of these , seven declined the decision aid because they had a clear treatment preference . The remaining 20 participants completed the decision aid ; 18 chose CMT , and two chose RT . All 20 patients wished to participate in the decision to some extent . All patients reported that using the decision support was useful to them and recommended its use for others . No patient or physician reported that the aid interfered with the physician-patient relationship . Patients ' 3-year SATs and median SATs were each strongly correlated with their strengths of treatment preference ( rho = 0.83 , P < .001 and rho = 0.67 , P = .02 , respectively ) . For all but one patient , either their 3-year or median survival threshold was consistent with their final treatment choice . Ten patients reported a stronger treatment preference after using the decision aid . CONCLUSION We conclude that implementing the decision-aid for patients with LA-NSCLC is feasible , that it demonstrates convergent validity , and that it is favorably evaluated by patients and their physicians . The aid seems to help patients underst and the benefits and risks of treatment and to choose the treatment that is most consistent with their values . Further evaluation of the aid is warranted Abstract Introduction . Stereotactic body radiation therapy ( SBRT ) for early stage non-small cell lung cancer ( NSCLC ) is now an accepted and patient friendly treatment , but still controversy exists about its comparability to conventional radiation therapy ( RT ) . The purpose of this single-institutional report is to describe survival outcome for medically inoperable patients with early stage NSCLC treated with SBRT compared with high dose conventional RT . Material and methods . From August 2005 to June 2012 , 100 medically inoperable patients were treated with SBRT at Odense University Hospital . The thoracic RT consisted of 3 fractions ( F ) of 15–22 Gy delivered in nine days . For comparison a group of 32 medically inoperable patients treated with conventional RT with 80 Gy/35–40  F ( 5 F/week ) in the period of July 1998 to August 2011 were analyzed . All tumors had histological or cytological proven NSCLC T1 - 2N0M0 . Results . The median overall survival was 36.1 months versus 24.4 months for SBRT and conventional RT , respectively ( p = 0.015 ) . Local failure-free survival rates at one year were in SBRT group 93 % versus 89 % in the conventional RT group and at five years 69 % versus 66 % , SBRT and conventional RT respectively ( p = 0.99 ) . On multivariate analysis , female gender and performance status of 0–1 and SBRT predicted improved prognosis . Conclusion . In a cohort of patients with NSCLC there was a significant difference in overall survival  favoring SBRT . Performance status of 0–1 , female gender and SBRT predicted improved prognosis . However , staging procedure , confirmation procedure of recurrence and technical improvements of radiation treatment is likely to influence outcomes . However , SBRT seems to be as efficient as conventional RT and is a more convenient treatment for the patients PURPOSE The aim of this guideline is to present recommendations regarding moderately hypofractionated ( 240 - 340 cGy per fraction ) and ultrahypofractionated ( 500 cGy or more per fraction ) radiation therapy for localized prostate cancer . METHODS AND MATERIAL S The American Society for Radiation Oncology convened a task force to address 8 key questions on appropriate indications and dose-fractionation for moderately and ultrahypofractionated radiation therapy , as well as technical issues , including normal tissue dose constraints , treatment volumes , and use of image guided and intensity modulated radiation therapy . Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and Society-approved tools for grading evidence quality and recommendation strength . RESULTS Based on high- quality evidence , strong consensus was reached for offering moderate hypofractionation across risk groups to patients choosing external beam radiation therapy . The task force conditionally recommends ultrahypofractionated radiation may be offered for low- and intermediate-risk prostate cancer but strongly encourages treatment of intermediate-risk patients on a clinical trial or multi-institutional registry . For high-risk patients , the task force conditionally recommends against routine use of ultrahypofractionated external beam radiation therapy . With any hypofractionated approach , the task force strongly recommends image guided radiation therapy and avoidance of nonmodulated 3-dimensional conformal techniques . CONCLUSIONS Hypofractionated radiation therapy provides important potential advantages in cost and convenience for patients , and these recommendations are intended to provide guidance on moderate hypofractionation and ultrahypofractionation for localized prostate cancer . The limits in the current evidentiary base-especially for ultrahypofractionation-highlight the imperative to support large-scale r and omized clinical trials and underscore the importance of shared decision making between clinicians and patients PURPOSE To compare the quality -adjusted life expectancy and overall survival in patients with Stage I non-small-cell lung cancer ( NSCLC ) treated with either stereotactic body radiation therapy ( SBRT ) or surgery .  METHODS AND MATERIAL S We constructed a Markov model to describe health states after either SBRT or lobectomy for Stage I NSCLC for a 5-year time frame . We report various treatment strategy survival outcomes stratified by age , sex , and pack-year history of smoking , and compared these with an external outcome prediction tool ( Adjuvant ! Online ) . RESULTS Overall survival , cancer-specific survival , and other causes of death as predicted by our model correlated closely with those predicted by the external prediction tool . Overall survival at 5 years as predicted by baseline analysis of our model is in favor of surgery , with a benefit ranging from 2.2 % to 3.0 % for all cohorts . Mean quality -adjusted life expectancy ranged from 3.28 to 3.78 years after surgery and from 3.35 to 3.87 years for SBRT . The utility threshold for preferring SBRT over surgery was 0.90 . Outcomes were sensitive to quality of life , the proportion of local and regional recurrences treated with st and ard vs. palliative treatments , and the surgery- and SBRT-related mortalities . CONCLUSIONS The role of SBRT in the medically operable patient is yet to be defined . Our model indicates that SBRT may offer comparable overall survival and quality -adjusted life expectancy as compared with surgical resection . Well-powered prospect i ve studies comparing surgery vs. SBRT in early-stage lung cancer are warranted to further investigate the relative survival , quality of life , and cost characteristics of both treatment paradigms PURPOSE Stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer ( NSCLC ) offers excellent control rates . Most published series deal mainly with small ( usually < 4 cm ) , peripheral , solitary tumors . Larger tumors are associated with poorer outcomes ( ie , lower control rates , higher toxicity ) when treated with conventional RT . It is unclear whether SBRT is sufficiently potent to control these larger tumors . We therefore evaluated and examined the influence of tumor size on treatment outcomes after SBRT . METHODS AND MATERIAL S Between October 2004 and October 2010 , 185 medically inoperable patients with early ( T1-T2N0M0 ) NSCLC were treated on a prospect i ve research ethics board-approved single-institution protocol . Prescription doses were risk-adapted based on tumor size and location . Follow-up included prospect i ve assessment of toxicity ( as per Common Terminology Criteria for Adverse Events , version 3.0 ) and serial computed tomography scans . Patterns of failure , toxicity , and survival outcomes were calculated using Kaplan-Meier method , and the significance of tumor size ( diameter , volume ) with respect to patient , treatment , and tumor factors was tested . RESULTS Median follow-up was 15.2 months . Tumor size was not associated with local failure but was associated with regional failure ( P=.011 ) and distant failure ( P=.021 ) . Poorer overall survival ( P=.001 ) , disease-free survival ( P=.001 ) , and cause-specific survival ( P=.005 ) were also significantly associated with tumor size ( with tumor volume more significant than diameter ) . Gross tumor volume and planning target volume were significantly associated with grade 2 or worse radiation pneumonitis . However , overall rates of grade ≥3 pneumonitis were low and not significantly affected by tumor or target size . CONCLUSIONS Currently employed stereotactic body radiation therapy dose regimens can provide safe effective local therapy even for larger solitary NSCLC tumors ( up to 5.7 cm in tumor diameter or 100 cm(3 ) in tumor volume ) but are associated with more nonlocal failures as well as poorer survival . These observations suggest these patients may benefit from more extensive staging or consideration of adjuvant therapy PURPOSE To present guidance for patients and physicians regarding the use of accelerated partial-breast irradiation ( APBI ) , based on current published evidence complemented by expert opinion . METHODS AND MATERIAL S A systematic search of the National Library of Medicine 's PubMed data base yielded 645 c and i date original research articles potentially applicable to APBI . Of these , 4 r and omized trials and 38 prospect i ve single-arm studies were identified . A Task Force composed of all authors synthesized the published evidence and , through a series of meetings , reached consensus regarding the recommendations contained herein . RESULTS The Task Force proposed three patient groups : ( 1 ) a " suitable " group , for whom APBI  outside of a clinical trial is acceptable , ( 2 ) a " caution ary " group , for whom caution and concern should be applied when considering APBI outside of a clinical trial , and ( 3 ) an " unsuitable " group , for whom APBI outside of a clinical trial is not generally considered warranted . Patients who choose treatment with APBI should be informed that whole-breast irradiation ( WBI ) is an established treatment with a much longer track record that has documented long-term effectiveness and safety . CONCLUSION Accelerated partial-breast irradiation is a new technology that may ultimately demonstrate long-term effectiveness and safety comparable to that of WBI for selected patients with early breast cancer . This consensus statement is intended to provide guidance regarding the use of APBI outside of a clinical trial and to serve as a framework to promote additional clinical investigations into the optimal role of APBI in the treatment of breast cancer PURPOSE Local failure rates after radiation therapy ( RT ) for locally advanced non-small-cell lung cancer ( NSCLC ) remain high . Consequently , RT dose intensification strategies continue to be explored , including hypofractionation , which allows for RT acceleration that could potentially improve outcomes . The maximum-tolerated dose ( MTD ) with dose-escalated hypofractionation has not been adequately defined . PATIENTS AND METHODS Seventy-nine patients with NSCLC were enrolled on a prospect i ve single-institution phase I trial of dose-escalated hypofractionated RT without concurrent chemotherapy . Escalation of dose per fraction was performed according to patients ' stratified risk for radiation pneumonitis with total RT doses ranging from 57 to 85.5 Gy in 25 daily fractions over 5 weeks using intensity-modulated radiotherapy . The MTD was defined as the maximum dose with ≤ 20 % risk of severe toxicity . RESULTS No grade 3 pneumonitis was observed and an MTD for acute toxicity was not identified during patient accrual . However , with a longer follow-up period , grade 4 to 5 toxicity occurred in six patients and was correlated with total dose ( P = .004 ) . An MTD was identified at 63.25 Gy in 25 fractions . Late grade 4 to 5 toxicities were attributable to damage to central and perihilar structures and correlated with dose to the proximal bronchial tree . CONCLUSION Although this dose-escalation model limited the rates of clinical ly significant pneumonitis , dose-limiting toxicity occurred and was dominated by late radiation toxicity involving central and perihilar structures . The identified dose-response for damage to the proximal bronchial tree warrants caution in future dose-intensification protocol s , especially when using hypofractionation PURPOSE The North Central Cancer Treatment Group performed a phase III trial to determine whether chemotherapy plus either bid radiation therapy ( RT ) or daily ( qd ) RT result ed in a better outcome for patients with stage III non-small-cell lung cancer ( NSCLC ) . No difference in survival was identified between the two arms . This secondary analysis was performed to examine the relationship between patient age and outcome . PATIENTS AND METHODS Two hundred forty-six patients were r and omized to receive etoposide plus cisplatin and either RT qd or split-course RT bid . This retrospective study compared the outcomes of patients aged > /=70 years ( " elderly patients ") with those of younger individuals . Of the 244 assessable patients , 63 ( 26 % ) were elderly , and 181 ( 74 % ) were younger individuals . RESULTS The 2-year and 5-year survival rates were 39 % and 18 % , respectively , in patients younger than 70 years , compared with 36 % and 13 % , respectively , in elderly patients ( P = .4 ) . Grade 4 + toxicity occurred in 62 % of patients younger than 70 years compared with 81 % of elderly patients ( P = .007 ) . Grade 4 + hematologic toxicity occurred in 56 % of patients younger than 70 years , compared with 78 % of elderly patients ( P = .003 ) . Grade 4 + pneumonitis occurred in 1 % of those younger than 70 years , compared with 6 % of elderly patients ( P = .02 ) . CONCLUSION Toxicity , especially myelosuppression and pneumonitis , was more pronounced in the elderly patients receiving combined-modality therapy for locally advanced NSCLC . Despite increased toxicity , elderly patients have survival rates equivalent to younger individuals . Therefore , fit , elderly patients with locally advanced NSCLC should be encouraged to receive combined-modality therapy , preferably on clinical trials with cautious , judicious monitoring . Future studies should explore ways to decrease toxicity of therapy in elderly patients Cis-Dichlorodiammine platinum ( II ) ( cis-DDP ) was demonstrated to be a potentiator of radiation therapy ( RT ) in experimental tumor models and in cultured cells . To assess the effectiveness of a combined modality treatment including RT and a weekly low-dose administration of cis-DDP , from January 1986 to June 1987 , 95 patients with unresectable locally advanced non-small cell carcinoma of the lung ( stage IIIa , b ) were r and omized for study . Fifty patients received RT alone at doses of 50 Gy ; 45 patients received the same RT plus cis-DDP 15 mg/m2 IV weekly . An overall response rate of 50 % and 64 % was observed in the RT and RT + cis-DDP group , respectively . No statistically significant differences were detected with regard to median survival time ( 11 months for RT v 16 months for RT + cis-DDP ) and progression-free interval ( 7 months in the RT arm v 9 months in the RT + cis-DDP arm ) , but the patterns of the first failure appeared to be affected by treatment . In fact , a lower number of intrathoracic relapses was observed in the RT + cis-DDP arm ( 12 in the RT + cis-DDP v 23 in the RT arm ) . Toxicity was mild and the feasibility of this schedule must be remarked . A better local control of disease can be obtained using cis-DDP as a radiation potentiator , but the true influence of this combined modality treatment on the length of survival , and the optimal cis-DDP timing and dosage are still to be evaluated in further clinical trials BACKGROUND AND PURPOSE To evaluate the benefits and the drawbacks of post-operative radiotherapy in completely resected Stage I ( a and b ) non-small cell lung cancer ( NSCLC ) . MATERIAL S AND METHODS Patients with pathological Stages Ia and Ib NSCLC have been r and omized into two groups : Group 1 ( G1 ) received adjuvant radiotherapy , Group 0 ( G0 ) the control group did not receive any adjuvant therapy .  Local control , toxicity and survival have been evaluated . RESULTS Between July 1989 and June 1997 , 104 patients with pathological stage I NSCLC have been enrolled in this study . Fifty-one patients were r and omized to G1 and 53 to G0 . Six patients have been excluded from the study due to incomplete follow-up data . Regarding local control , one patient in the G1 group had a local recurrence ( 2.2 % ) while in the G0 12 local recurrences have been observed ( 23 % ) . Seventy-one percent of patients are disease-free at 5 years in G1 and 60 % in G0 ( P=0.039 ) . Overall 5-year survival ( Kaplan-Meier ) showed a positive trend in the treated group : 67 versus 58 % ( P=0.048 ) . Regarding toxicity in G1 , six patients experienced a grade 1 acute toxicity . Radiological evidence of long-term lung toxicity , with no significant impairment of the respiratory function , has been detected in 18 of the 19 patients who have been diagnosed as having a post-radiation lung fibrosis . CONCLUSIONS Adjuvant radiotherapy gave good results in terms of local control in patients with completely resected NSCLC with pathological Stage I. Overall 5-year survival and disease-free survival showed a promising trend . Treatment-related toxicity is acceptable OBJECTIVES Stage III non-small cell lung cancer ( NSCLC ) describes a heterogeneous population with disease presentation ranging from apparently resectable tumors with occult microscopic nodal metastases to unresectable , bulky nodal disease . This review up date s the published clinical trials since the last American College of Chest Physicians guidelines to make treatment recommendations for this controversial subset of patients . METHODS Systematic search es were conducted through MEDLINE , Embase , and the Cochrane Data base for Systematic Review up to December 2011 , focusing primarily on r and omized trials , selected meta-analyses , practice guidelines , and review s. RESULTS For individuals with stage IIIA or IIIB disease , good performance scores , and minimal weight loss , treatment with combined chemoradiotherapy results in better survival than radiotherapy alone . Consolidation chemotherapy or targeted therapy following definitive chemoradiation for stage IIIA is not supported . Neoadjuvant therapy followed by surgery is neither clearly better nor clearly worse than definitive chemoradiation . Most of the arguments made regarding patient selection for neoadjuvant therapy and surgical resection provide evidence for better prognosis but not for a beneficial impact of this treatment strategy ; however , weak comparative data suggest a possible role if only lobectomy is needed in a center with a low perioperative mortality rate . The evidence supports routine platinum-based adjuvant chemotherapy following complete resection of stage IIIA lung cancer encountered unexpectedly at surgery . Postoperative radiotherapy  improves local control without improving survival . CONCLUSIONS Multimodality therapy is preferable in most subsets of patients with stage III lung cancer . Variability in the patients included in r and omized trials limits the ability to combine results across studies and thus limits the strength of recommendations in many scenarios . Future trials are needed to investigate the roles of individualized chemotherapy , surgery in particular cohorts or setting s , prophylactic cranial radiation , and adaptive radiation BACKGROUND Many patients with locally advanced non-small cell lung cancer ( NSCLC ) can not undergo concurrent chemotherapy because of comorbidities or poor performance status . Hypofractionated radiation regimens , if tolerable , may provide an option to these patients for effective local control . METHODS AND MATERIAL S Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy ( PBT ) from September 2010 through July 2012 . Eligible patients had histologically documented lung cancer , thymic tumors , carcinoid tumors , or metastatic thyroid tumors .  Concurrent chemotherapy was not allowed , but concurrent treatment with biologic agents was . The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectiveness [RBE])/fraction , 3.5 Gy(RBE)/fraction , or 4 Gy(RBE)/fraction . Dose constraints were derived from biologically equivalent doses of st and ard fractionated treatment . RESULTS The median follow-up time for patients alive at the time of analysis was 13 months ( range , 8 - 28 months ) . Fifteen patients received treatment to hilar or mediastinal lymph nodes . Two patients experienced dose-limiting toxicity possibly related to treatment ; 1 received 3.5-Gy(RBE ) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab . The other patient received 4-Gy(RBE ) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT . CONCLUSION Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures . Phase 2/3 trials are needed to compare the efficacy of this technique with st and ard treatment for locally advanced NSCLC PURPOSE Late gastrointestinal ( GI ) and genitourinary ( GU ) morbidity from external beam irradiation used to treat adenocarcinoma of the prostate continue to be a concern of physicians and patients alike . In addition , for locally advanced/high-risk cancer , the appropriate use of hormonal manipulation in addition to radiation therapy ( RT ) may increase toxicity . We analyzed three large Radiation Therapy Oncology Group ( RTOG ) studies ( 85 - 31 , 86 - 10 , and 92 - 02 ) to try to address these issues . METHODS AND MATERIAL S A total of 2,922 patients were accrued with a median follow-up of 10.3 years for surviving patients . The RTOG scoring scheme was used to assess GI , GU , and other toxicities . Toxicity reported was Grade 3 or higher late toxicity . Patient toxicity level was assessed by study and by treatment type combining RT only vs. RT + short-course hormone therapy ( STH ) vs. RT + long-term hormone therapy ( LTH ) . RESULTS Multivariate analysis reveals that age > 70 was statistically significantly associated with a decrease in late any Grade 3 + toxicity ( hazard ratio [ HR ] = 0.78 , p = 0.0476 ) adjusted for treatment type . Comparing treatment type , patients treated with RT+STH had a statistically significant lower probability of Grade 3 + GI , GU , and other toxicity compared with RT alone ( p = .00006 ; p = 0.0037 ; p = 0.0127 , respectively ) . Patients treated with RT+LTH had a statistically significant lower probability of Grade 3 + GU toxicity compared with RT alone ( p = 0.023 ) . CONCLUSIONS These data show that external beam radiation therapy remains a safe option for locally advanced/high-risk prostate cancer , and the use of hormonal manipulation does appear to be protective for GU and GI toxicity depending upon length of treatment PURPOSE To investigate the efficacy of concurrent hyperfractionated radiation therapy ( HFX RT ) and low-dose daily chemotherapy ( CHT ) in stage III non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Between January 1990 and December 1991 , 131 patients with histologically or cytologically confirmed stage III NSCLC , Karnofsky performance status ( KPS ) > or = 50 , and no previous therapy were r and omly treated as follows : group I , HFX RT with 1.2 Gy twice daily to a total dose of 69.6 Gy ( n = 66 ) ; and group II , same HFX RT with CHT consisting of 50 mg of carboplatin ( CBDCA ) and 50 mg of etoposide ( VP-16 ) given on each RT day ( n = 65 ) . RESULTS Group II patients had a significantly longer survival time than group I patients , with a median survival of 22 versus 14 months and 4-year survival rates of 23 % versus 9 % ( P = .021 ) . The median time to local recurrence and 4-year local recurrence-free survival rate were also significantly higher in group II than in group I ( 25 v 20 months and 42 % v 19 % respectively , P = .015 ) . In contrast , the distant metastasis-free survival rate did not significantly differ in the two groups ( P = .33 ) . The two groups showed similar incidence of acute and late high- grade toxicity ( P = .44 and .75 , respectively ) . No treatment-related toxicity was observed . CONCLUSION The combination of HFX RT and low-dose daily CBDCA plus VP-16 was tolerable and improved the survival of patients with stage III NSCLC as a result of improved local control Purpose The purpose of this phase I/II study was to evaluate the feasibility and efficacy of S-1 plus cisplatin at the recommended schedule with concurrent thoracic radiotherapy for locally advanced non-small cell lung cancer ( LA-NSCLC ) . Methods Eligible patients with LA-NSCLC were treated with cisplatin intravenously at a dose of 60 mg/m2 on day 8 plus oral S-1 at a dosage of 40 mg/m2 twice per day for two different treatment schedules for up to 4 cycles . Patients also concurrently received 60 Gy of thoracic radiation in 30 fractions . The primary endpoint of the phase II study was the proportion of patients who survived for more than 2 years . Results Between August 2005 and October 2010 , a total of 45 patients were enrolled in this phase I/II study ; their long-term survival was then followed for a median period of 5.8 years . Nineteen of the 39 patients in the phase II study survived for more than 2 years and met the primary endpoint of the study . The median overall survival period was 24.9 months [ 95 % confidence interval ( CI ) 17.4–74.5 months ] , and the 2- and 5-year overall survival rates were 51.0 and 43.0 % , respectively . The response rate was 85 % , and the median progression-free survival period was 13.8 months ( 95 % CI 9.5–27.1 months ) . Hematological toxicity was mild . Grade 3 febrile neutropenia and pneumonitis was observed in 5 and 5 % , respectively . Conclusion Our study indicated that S-1 plus cisplatin with concurrent thoracic radiotherapy yielded encouraging survival outcomes and an acceptable safety profile for LA-NSCLC PURPOSE Radiation Therapy Oncology Group ( RTOG ) Protocol 92 - 02 was a r and omized trial testing long-term ( LT ) adjuvant and rogen deprivation ( AD ) after initial AD with external-beam radiotherapy ( RT ) in patients with locally advanced prostate cancer ( PC ; T2c-4 ) and with prostate-specific antigen level less than 150 ng/mL. PATIENTS AND METHODS Patients received a total of 4 months of goserelin and flutamide , 2 months before and 2 months during RT . A radiation dose of 65 to 70 Gy was given to the prostate and a dose of 44 to 50 Gy to the pelvic lymph nodes . Patients were r and omly assigned to receive no additional therapy ( short-term [ST]AD-RT ) or 24 months of goserelin ( LTAD-RT ) ; 1,554 patients were entered onto the study . RESULTS The LTAD-RT arm showed significant improvement in all efficacy end points except overall survival ( OS ; 80.0 % v 78.5 % at 5 years , P = .73 ) , compared with the STAD-RT arm . In a subset of patients not part of the original study design , with tumors assigned Gleason scores of 8 to 10 by the contributing institutions , the LTAD-RT arm had significantly better OS ( 81.0 % v 70.7 % , P = .044 ) . There was a small but significant increase in the frequency of late radiation grade s 3 , 4 , and 5 gastrointestinal toxicity ascribed to the LTAD-RT arm ( 2.6 % v 1.2 % at 5 years , P = .037 ) , the cause of which is not clear . CONCLUSION The RTOG 92 - 02 trial supports the addition of LT adjuvant AD to STAD with RT for T2c-4 PC . In the exploratory subset analysis of patients with Gleason scores 8 to 10 , LT adjuvant AD result ed in a survival advantage BACKGROUND Combined radiochemotherapy is the gold st and ard for patients with locally advanced non-small cell lung cancer ( LA-NSCLC ) . In the present study , the feasibility of hypofractionated accelerated radiotherapy with cytoprotection ( HypoARC ) in combination with vinorelbine and liposomal doxorubicin was evaluated . PATIENTS AND METHODS Fourteen patients ( pts ) with LA-NSCLC ( PS 0 - 2 ) were recruited . Patients received 15 fractions for 3.5 Gy within four consecutive weeks ( 1 week split after the 10th fraction ) , supported with subcutaneously administered amifostine ( 500 - 1000 mg/day ) . Pegylated liposomal doxorubicin was administered at a st and ard dose of 20 mg/m2 every two weeks , for 3 consecutive cycles . Vinorelbine was administered at 3 dose levels : a ) 20 mg/m2 every week ( 5 pts ) , b ) 25 mg/m2 thrice every two weeks ( 5 pts ) and c ) 30 mg/m2 thrice every two weeks ( 4 pts ) . RESULTS Grade 3 neutropenia enforcing chemotherapy delays was noted in 2/5 and 2/4 patients in the groups b and c respectively . Fatigue was a common but not dose-defining feature . Radiation grade 2 esophagitis was noted in 6/14 patients . No case of severe radiation pneumonitis was noted . Partial response was documented in 9/14 patients , minimal response in 3/14 and stable disease in 2/14 . The median local progression-free survival was 12 months and the median overall survival was 8 months . CONCLUSION It is concluded that the administration of 25 mg/m2 of vinorelbine thrice a week together with liposomal doxorubicin and thoracic radiotherapy is feasible for patients with LA-NSCLC , providing high response rates . Further studies are required to better assess benefits in terms of local and distant control of the disease OBJECTIVE To evaluate recurrence and survival associated with adjuvant carboplatin and paclitaxel chemotherapy interposed with involved field radiation for advanced endometrial cancer . METHOD This is a prospect i ve cohort study of women with Stage III and IV endometrial cancer treated at a single institution between April 2002 and July 2006 .  Adjuvant therapy consisted of 4 cycles of intravenous paclitaxel ( 175 mg/m(2 ) ) and carboplatin ( 350 mg/m(2 ) ) every 3 weeks , followed by external beam radiotherapy ( RT ) to the pelvis ( 45 Gy ) , then another 2 cycles of chemotherapy . Para-aortic RT and /or HDR vault brachytherapy were added at the discretion of the treating physician . Toxicity of this protocol was previously reported . Primary endpoints for this study were disease-free and overall survival rates . RESULTS Forty-three patients with a median age of 64 years ( 46 - 83 years ) were evaluated . The majority had Stage IIIC disease ( 63 % ) , and the most common histology was serous carcinoma ( 49 % ) . Six cycles of combination chemotherapy were completed in 81 % , and all patients completed pelvic RT . Median follow-up was 30 months ( 9 - 71 months ) . Twenty-one patients ( 49 % ) recurred at a median of 17 months ( 7 - 62 months ) . There were only 3 local recurrences , including 2 in the pelvis and 1 in the vagina/vulva . Median disease-free survival ( DFS ) was 50 months and median overall survival ( OS ) has not been reached . Three year DFS and OS rates were 53 % and 68 % , respectively . CONCLUSION Adjuvant carboplatin and paclitaxel chemotherapy interposed with involved field radiation is associated with a low rate of local recurrence and favorable survival for advanced endometrial cancer PURPOSE Neoadjuvant chemotherapy ( NACT ) and radical surgery ( RS ) have emerged as a possible alternative to conventional radiation therapy ( RT ) in locally advanced cervical carcinoma . In 1990 , a phase III trial was undertaken to verify such a hypothesis in terms of survival and treatment-related morbidity . PATIENTS AND METHODS Patients with squamous cell , International Federation of Gynecology and Obstetrics stage IB2 to III cervical cancer were eligible for the study . They received cisplatin-based NACT followed by RS ( type III to V radical hysterectomy plus systematic pelvic lymphadenectomy ) ( arm A ) or external-beam RT ( 45 to 50 Gy ) followed by brachyradiotherapy ( 20 to 30 Gy ) ( arm B ) . RESULTS Of 441 patients r and omly assigned to NACT+RS or RT , eligibility was confirmed in 210 and 199 patients , respectively . Treatment was administered according to protocol in 76 % of arm A patients and 72 % of arm B patients . Adjuvant treatment was delivered in 48 operated patients ( 29 % ) . There was no evidence for any significant excess of severe morbidity in one of the two arms . The 5-year overall survival ( OS ) and progression-free survival ( PFS ) rates were 58.9 % and 55.4 % for arm A and 44.5 % and 41.3 % for arm B ( P = .007 and P = .02 ) , respectively . Subgroup survival analysis shows OS and PFS rates of 64.7 % and 59.7 % ( stage IB2-IIB , NACT+RS ) , 46.4 % and 46.7 % ( stage IB2-IIB , RT ) ( P = .005 and P = .02 ) , 41.6 % and 41.9 % ( stage III , NCAT+RS ) , 36.7 % and 36.4 % ( stage III , RT ) ( P = .36 and P = .29 ) , respectively . Treatment had a significant impact on OS and PFS . CONCLUSION Although significant only for the stage IB2 to IIB group , a survival benefit seems to be associated with the NACT+RS compared with conventional RT
RESULTS For patients who have undergone surgical resection , high-level evidence suggests that use of postoperative RT does not influence survival , but optimizes local control for patients with N2 involvement , and its use in the setting of positive margins or gross primary /nodal residual disease is recommended .
No high-level evidence exists for the routine use of preoperative induction chemoradiation therapy ; however , modern surgical series and a post-hoc Intergroup 0139 clinical trial analysis suggest that a survival benefit may exist if patients are properly selected and surgical techniques/postoperative care is optimized .
PURPOSE To provide guidance to physicians and patients with regard to the use of adjuvant external beam radiation therapy ( RT ) in locally advanced non-small cell lung cancer ( LA NSCLC ) based on available medical evidence complemented by consensus-based expert opinion .