RESULTSKQ1: What is the ideal external beam dose fraction-ation for the curative-intent treatment o f locally advanced non-small cell lung cancer with radiation therapy alone?对于局部进展期肺癌根治性单纯性放疗的最佳剂量？Guideline StatementsA. Radiotherapy alone has been shown to be supe-rior to observation strategies or chemotherapy alone for LA NSCLC in terms of overall survival but at the cost of treatment-related side effects s uch as esophagitis and pneumonitis (MQE, recom-mendation rated as “Strong”).B. Radiotherapy alone may be used as definitive radical treatment for patients with LA NSCLC w ho are ineligible for combined modality therapy (i.e. due to poor performance status, medical com orbidity, extensive weight loss, and/or patient preferences) but with a tradeoff of survival for improved treatment tolerability (HQE, recommen-dation rated as “Strong”).C.In the context of conventionally fractionated radio-therapy, a minimum dose of 60 Gy is recom mend-ed to optimize important clinical outcomes such as local control (HQE, recommendation rat ed as “Strong”).D. Altered fractionation schedules that have been explored in the medical literature include hyperf ractionation (lower dose per fraction over the standard treatment duration), accelerated fractionatio n (con-ventional fraction size and same total dose, given in a shorter period of time), accelerated hyperfrac-tionation (combination of these two), and hypo-fractionation (higher dose per fraction a nd fewer fractions). (No evidence rating, recommenda-tion rated as “Strong”).E.Specific altered fractionation schemes that have been investigated in various comparative effec-tiveness research investigations (including ran-domized controlled trials) include 45 Gy/15 frac-tio ns (hypofractionation), 69.6 Gy/58 fractions BID (hyperfractionation), 54 Gy/36 fractions TID ove r 12 consecutive days (CHART, accelerated hy-perfractionation), and 60 Gy/40 fractions TID over 18 days (CHARTWEL, accelerated hyperfraction-ation). (No evidence rating, recommendation ra ted as “Strong”)KQ2: What is the ideal external beam dose fraction-ation for the curative-intent treatment of locall y advanced non-small cell lung cancer with chemora-diotherapy?对于局部进展期肺癌根治性同期放化疗的最佳剂量？Guideline StatementsA. The standard thoracic radiotherapy dose-fraction-ation for patients treated with concurrent che mo-therapy is 60 Gy given in 2 Gy once daily fractions over 6 weeks (MQE, recommendation rate d as “Strong”).B. Dose escalation beyond 60 Gy with conventional fractionation has not been demonstrated to b e as-sociated with any clinical benefits including over-all survival (MQE, recommendation rated a s “Strong”).C. Hyperfractionated radiotherapy regimens that do not result in acceleration of the treatment cou rse, even though the total nominal radiotherapy dose may be modestly increased, do not appear t o im-prove outcomes compared with conventionally fractionated therapy (MQE, recommendatio n rated as “Strong”).D.The optimal thoracic radiotherapy regimen for patients receiving sequential chemotherapy and r adiotherapy is not known; however results from the CHARTWEL and HART phase III studies sug -gest that increasing the biologic equivalent dose by using accelerated hyperfractionated radiotherapy may be of benefit following induction chemother-apy in locally advanced non-small cell lun g cancer (MQE, recommendation rated as “Strong”).E. Although the impact of increasing the predicted bi-ologic equivalent dose via accelerated radio therapy regimens is not clear, further study of accelerated hypofractionated regimens is of interes t to opti-mize the therapeutic ratio of treatment, particularly in the context of advanced imaging, ra diotherapy planning, and treatment delivery. (No evidence rating, recommendation rated as “Stro ng”)KQ3: What is the ideal timing of external beam radiation therapy in relation to systemic che mo-therapy for the curative-intent treatment of locally advanced non-small cell lung cancer? 对于局部进展期肺癌根治性放-化疗的最佳顺序？Guideline StatementsA. There is phase III evidence demonstrating improved overall survival, local control, and respons e rate associated with concurrent chemoradiation when compared against sequential chemotherap y fol-lowed by radiation (HQE, recommendation rated as “Strong”).B. There is no proven role for the routine use of induction chemotherapy prior to chemoradiothera py, although, this treatment paradigm can be considered for the management of bulky tumors to all ow for radical planning after chemotherapy response (MQE, recommendation rated as “Strong”).C.There are no phase III data specifically supporting the role for consolidation chemotherapy afte r chemoradiotherapy for the improvement of overall survival; however, this treatment is still routi nely given to manage potential micrometastatic disease particularly if full systemic chemotherap y doses were not delivered during radiotherapy (LQE, rec-ommendation rated as “Strong”).D.For patients that cannot tolerate concurrent chemo-radiotherapy, sequential chemotherapy follo wed by radical radiation has been shown to be associ-ated with an overall survival benefit when c om-pared to radiotherapy alone (HQE, recommenda-tion rated as “Strong”).E. The ideal concurrent chemotherapy regimen has not been determined; however, the two most c om-mon regimens (cisplatin/etoposide and carbopla-tin/paclitaxel) are the subject of a complete d phase III clinical trial (NCT01494558). (No evidence rating, recommendation rated as “Stron g”)KQ4: What are the indications for adjuvant postoperative radiotherapy for the curative-inte nt treatment of locally advanced non-small cell lung cancer?辅助放疗的适应症：Guideline StatementsA. Phase III studies and meta-analyses of postopera-tive radiotherapy (PORT) in completely resect ed (R0) LA NSCLC with N2 disease suggest that its addition to surgery does not improve overall s ur-vival but may improve local control when com-pared to observation strategies (MQE, recomme n-dation rated as “Strong”).B. Phase III studies and meta-analyses of PORT in completely resected (R0) LA NSCLC with N0 -1 disease demonstrate inferior survival when com-pared to observation strategies; therefore, POR T therapy for this patient population is not routinely recommended. (MQE, recommendation rate d as “Strong”).C. Since level 1 evidence supports the administration of adjuvant chemotherapy for completely res ected (R0) LA NSCLC based on improvements in over-all survival compared to patients on observ ation, any PORT therapy should be delivered sequentially after chemotherapy in order not to interf ere with standard of care chemotherapy (LQE, recommen-dation rated as “Strong”).D. For patients receiving adjuvant PORT for R0 dis-ease, conventionally fractionated doses in th e range of 50 Gy to 54 Gy (in 1.8 Gy-2.0 Gy/day) should be utilized (LQE, recommendation rate d as “Strong”).E. Patients with microscopic residual (R1) primary disease (i.e., positive margin) and/or microsco pic (i.e., extra-capsular extension) nodal disease may be appropriate candidates for PORT (given e ither concurrently or sequentially with chemotherapy) with conventionally fractionated doses in th e range of 54 Gy to 60 Gy (in 1.8 Gy-2.0 Gy/day fraction size) in order to improve local control (L QE, rec-ommendation rated as “Strong”).F. Patients with gross residual primary and/or mac-roscopic nodal (R2) disease of LA NSCLC ma y be appropriate candidates for PORT (given either concurrently or sequentially with chemotherap y) with conventionally fractionated doses of at least 60 Gy (in 1.8-2.0 Gy/day fraction size) in ord er to improve local control (LQE, recommendation rated as “Strong”).KQ5: When is neoadjuvant radiotherapy prior to surgery indicated for the curative-intent treatmen t of locally advanced non-small cell lung cancer?新辅助放疗的适应症？Guideline StatementsA. There is no level I evidence recommending the use of induction radiotherapy (or chemoradioth erapy) followed by surgery for patients with resectable stage III NSCLC (HQE, recommendatio n rated as “Strong”).B. In those patients who are selected for trimodality approach, preoperatively planned lobectom y (as opposed to pneumonectomy), based on best surgi-cal judgment is preferable since it was asso ciated with survival benefit in the exploratory post-hoc INT 0139 analysis (MQE, recommendatio n rat-ed as “Strong”).C. No definitive statement can be made about best patient selection criteria for the trimodality the rapy, although no weight loss, female gender, and one (vs. more) involved nodal stations were ass ociated with improved outcome in INT 0139 (MQE, rec-ommendation rated as “Strong”).D. The ideal preoperative radiotherapy dose is cur-rently not known; however, a minimum of 45 Gy should be delivered consistent with the INT 0139 trial (LQE, recommendation rated as “Str ong”).E. Preoperative conventionally fractionated doses up to 60 Gy (in 2 Gy/day) may be associated w ith rea-sonable mediastinal clearance rates, although no significant correlation with improved over all sur-vival has been demonstrated (LQE, recommenda-tion rated as “Strong”).。
