Second primary lung cancers following a diagnosis of primary head and neck cancer.

OBJECTIVES: Second primary lung cancers (SPLC) are not uncommon in survivors of squamous cell head and neck cancer (HNSCC), and carry a worse prognosis than when patients present with a primary lung cancer. We reviewed our institutional experience on the treatment and prognosis of SPLC patients, both at the time of diagnosis, and following treatment of HNSCC, in order to explore treatment outcomes. MATERIALS AND METHODS: Our institutional database was queried for patients with a diagnosis of HNSCC and lung cancer, between 2000 and 2013. Only HNSCC patients with tumors of the oral cavity, oropharynx, hypopharynx and larynx were eligible. Patients were stratified between synchronous and metachronous HNSCC and SPLC. Cox regression analysis was performed to determine factors predictive of overall survival (OS) in metachronous presentations. RESULTS: 181 eligible patients were identified for analysis, comprising 40 synchronous and 141 metachronous HNSCC-SPLC. Patients presenting with synchronous SPLC were more likely to have early-stage disease, as compared to patients with metachronous SPLC (45% vs. 28%, respectively; p=0.036). Patients with early stage SPLC had a significantly better survival compared to those with locally advanced (p<0.001) and metastatic disease (p<0.001), with a median OS of 95.4 months vs. 11.0 and 4.6 months, respectively. CONCLUSIONS: Although the survival of patients treated for early-stage NSCLC were good, the OS of the entire cohort of SPLC after HNSCC was poor as a majority of patients presented with advanced disease. The use of CT screening strategies in this patient population warrants further investigation.

A brief report on outcomes of stereotactic ablative radiotherapy for a second primary lung cancer: evidence in support of routine CT surveillance.

New guidelines recommend the use of CT surveillance after a curative treatment for lung cancer as survivors have a 3-6% risk per person year of developing a second primary lung cancer. Our analysis of 107 patients with second primary lung cancer treated by stereotactic ablative radiotherapy showed a comparable 3 years overall survival (60%) and local control rate (89%) as for an initial lung cancer. Toxicity was uncommon, despite the fact that 73% of patients had undergone a prior (bi)lobectomy. Our findings indicate that CT surveillance is also appropriate in patients who may be unfit, or unwilling, to undergo surgery.

High-dose, conventionally fractionated thoracic reirradiation for lung tumors.

BACKGROUND: Loco-regional recurrences and second primary lung tumors are not uncommon after high-dose thoracic radiotherapy. The availability of improved radiotherapy techniques increases options for reirradiation. We describe a single-institutional experience with high-dose conventional thoracic reirradiation for both loco-regional recurrences and new primary tumors. METHODS: Retrospective chart review of patients undergoing reirradiation between February 2004 and February 2013. RESULTS: Of 24 patients identified, 54% had a loco-regional recurrence, and 46% a new primary tumor. The majority (63%) had stage III NSCLC at both initial and second treatment; median interval between treatments was 51 months (5-189), median follow-up after reirradiation was 19.3 months (95% CI: 2.8-35.9). Median overall survival (OS) after reirradiation was 13.5 months, with 1-year survival 51%. Median event-free survival (EFS) was 8.4 months. Median time between reirradiation and local progression (n=8) or distant progression (n=8) was 6.7 and 11.8 months, respectively. Three patients died with possible grade 5 bleeding. Other toxicities were uncommon. Planning target volume (PTV) at reirradiation was the most important prognostic factor; PTV <300 versus ≥300cc was significantly associated with median OS (17.4 vs 8.2 months, p=0.03) and EFS (14.1 vs 5.5 months, p=0.03). Magnitude of overlap between the initial and subsequent PTVs, and between dose distributions, did not influence survival. CONCLUSION: Thoracic reirradiation with high dose conventional radiotherapy appears to deliver a meaningful survival benefit in low volume new primary or recurrent lung cancer. Further studies are needed to confirm these findings, and to establish reliable normal tissue tolerance doses for reirradiation.

Radical treatment of synchronous oligometastatic non-small cell lung carcinoma (NSCLC): patient outcomes and prognostic factors.

OBJECTIVES: Metastatic non-small cell lung carcinoma (NSCLC) generally carries a poor prognosis, and systemic therapy is the mainstay of treatment. However, extended survival has been reported in patients presenting with a limited number of metastases, termed oligometastatic disease. We retrospectively reviewed the outcomes of such patients treated at two centers. MATERIALS AND METHODS: From September 1999-July 2012, a total of 61 patients with 1-3 synchronous metastases, who were treated with radical intent to all sites of disease, were identified from records of two cancer centers. Treatment was considered radical if it involved surgical resection and/or delivery of radiation doses ≥13 × 3 Gy. RESULTS: Besides the primary tumor, 50 patients had a solitary metastasis, 9 had two metastases, and 2 had three metastases. Locations of metastases included the brain (n = 36), bone (n = 11), adrenal (n = 4), contralateral lung (n = 4), extra-thoracic lymph nodes (n = 4), skin (n = 2) and colon (n = 1). Only one patient had metastases in two different organs. Median follow-up was 26.1 months (m), median overall survival (OS) was 13.5m, median progression free survival (PFS) was 6.6m and median survival after first progression (SAFP) was 8.3m. The 1- and 2-year OS were, 54% and 38%, respectively. Significant predictors of improved OS were: smaller radiotherapy planning target volume (PTV) (p = 0.004) and surgery for the primary lung tumor (p < 0.001). Factors associated with improved SAFP included surgery for the primary lung tumor, presence of brain metastases, and absence of bone metastases. No significant differences in outcomes were observed between the two centers. CONCLUSION: Radical treatment of selected NSCLC patients presenting with 1-3 synchronous metastases can result in favorable 2-year survivals. Favorable outcomes were associated with intra-thoracic disease status: patients with small radiotherapy treatment volumes or resected disease had the best OS. Future prospective clinical trials, ideally randomized, should evaluate radical treatment strategies in such patients.

Treatment of multiple primary lung cancers using stereotactic radiotherapy, either with or without surgery.

BACKGROUND AND PURPOSE: Multiple primary lung cancers (MPLC) are not an uncommon presentation. Current guidelines recommend a curative approach when early-stage MPLC is diagnosed as favorable outcomes have been reported after surgery. We studied outcomes following stereotactic ablative radiotherapy (SABR). MATERIALS AND METHODS: Following review of imaging and pathology at a multi-disciplinary tumor board, a total of 62 patients were referred for SABR with a diagnosis of synchronous MPLC. SABR was performed for both lesions in 56 patients, while another 6 underwent SABR for only one lesion and surgery for the other lesion. A total dose of 54-60 Gy was delivered in 3-8 fractions. RESULTS: Median follow-up was 44 months (95% CI: 29-59). Overall survival of all patients was 31 months (95% CI: 17-44), with an actuarial 2-year survival of 56%. No grade 4 or 5 post-SABR toxicity was observed. Local control rates calculated per lesion, were 84% at 2 years, and 78% at 3 years. The two-year actuarial regional control rate was 87%. CONCLUSIONS: SABR for synchronous MPLC achieves a lesion control rate of 84% after 2 years, with limited toxicity. SABR should be considered when patients with lung cancer present with a synchronous second lesion and no nodal involvement.

Comparing rigid and deformable dose registration for high dose thoracic re-irradiation.

For patients with locally-recurrent lung cancer, high dose thoracic re-irradiation can prolong survival. Deformable image registration improves the accuracy with which initial treatments are accounted for compared to rigid image registration. Using deformable image registration will improve correlative toxicity data, and may reduce toxicity for selected patients undergoing re-irradiation.

Stereotactic ablative radiotherapy for comprehensive treatment of oligometastatic tumors (SABR-COMET): study protocol for a randomized phase II trial.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control. Survival outcomes for patients with oligometastatic disease treated with SABR appear promising, but conclusions are limited by patient selection, and the lack of adequate controls in most studies. The goal of this multicenter randomized phase II trial is to assess the impact of a comprehensive oligometastatic SABR treatment program on overall survival and quality of life in patients with up to 5 metastatic cancer lesions, compared to patients who receive standard of care treatment alone. METHODS: After stratification by the number of metastases (1-3 vs. 4-5), patients will be randomized between Arm 1: current standard of care treatment, and Arm 2: standard of care treatment + SABR to all sites of known disease. Patients will be randomized in a 1:2 ratio to Arm 1:Arm 2, respectively. For patients receiving SABR, radiotherapy dose and fractionation depends on the site of metastasis and the proximity to critical normal structures. This study aims to accrue a total of 99 patients within four years. The primary endpoint is overall survival, and secondary endpoints include quality of life, toxicity, progression-free survival, lesion control rate, and number of cycles of further chemotherapy/systemic therapy. DISCUSSION: This study will provide an assessment of the impact of SABR on clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with oligometastatic disease, and will inform the design of a possible phase III study.