There is phase III evidence demonstrating improved overall survival, local control, and response rate associated with concurrent chemoradiotherapy when compared against sequential chemotherapy followed by radiation.

For patients who cannot tolerate concurrent chemoradiotherapy, sequential chemotherapy followed by radical radiation has been shown to be associated with an overall survival benefit when compared with radiotherapy alone.

Radiotherapy alone may be used as definitive radical treatment for patients with LA NSCLC who are ineligible for combined-modality therapy (i.e., due to poor performance status, medical comorbidity, extensive weight loss, and/or patient preferences) but with a trade-off of survival for improved treatment tolerability.

There is no proven role for the routine use of induction chemotherapy before chemoradiotherapy; although, this treatment paradigm can be considered for the management of bulky tumors to allow for radical planning after chemotherapy response.

There are no phase III data specifically supporting the role for consolidation chemotherapy after chemoradiotherapy for the improvement of overall survival; however, this treatment is still routinely given to manage potential micrometastatic disease particularly if full systemic chemotherapy doses were not delivered during radiotherapy.

The ideal concurrent chemotherapy regimen has not been determined; however, the two most common regimens (cisplatin/etoposide and carboplatin/paclitaxel) are the subject of a completed phase III clinical trial (NCT01494558).

In the context of conventionally fractionated radiotherapy, a minimum dose of 60 Gy is recommended to optimize important clinical outcomes such as local control.

The standard thoracic radiotherapy dose-fractionation for patients treated with concurrent chemotherapy is 60 Gy given in 2 Gy once daily fractions over 6 weeks.

Dose escalation beyond 60 Gy with conventional fractionation has not been demonstrated to be associated with any clinical benefits including overall survival.

Phase III studies and meta-analyses of postoperative radiotherapy in completed resected (R0) LA NSCLC with N2 disease suggest that its addition to surgery does not improve overall survival but may improve local control when compared with observation strategies.

Phase III studies and meta-analyses of postoperative radiotherapy in completely resected (R0) LA NSCLC with N0-1 disease demonstrate inferior survival when compared with observation strategies; therefore, postoperative radiotherapy for this patient population is not recommended.

There is no level I evidence recommending the use of induction radiotherapy (or chemoradiotherapy) followed by surgery for patients with resectable stage III NSCLC.

In those patients who are selected for trimodality approach, preoperatively planned lobectomy (as opposed to pneumonectomy), based on best surgical judgment, is preferable, since it was associated with survival benefit in the exploratory posthoc North American Intergroup study INT 0139 analysis.

No definitive statement can be made about best patient selection criteria for the trimodality therapy, although no weight loss, female gender, and one (v more) involved nodal stations were associated with improved outcome in INT 0139.