Alexander Y. Sun

Localized Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiation Therapy Has Excellent Clinical Outcome

PURPOSEnExtranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a distinct lymphoma with unique clinicopathologic features. We report the clinical outcome of stage I and II MALT lymphoma treated with involved field radiation therapy (RT).nnnPATIENTS AND METHODSnFrom 1989 to 2000, 103 patients with stage IE and IIE disease were referred. Their median age was 60 years, with a 2:1 female predominance. Presenting sites were stomach (17 patients), orbital adnexa (31 patients), salivary glands (24 patients), thyroid gland (13 patients), and other sites (18 patients). Ninety-three patients received RT--85 received RT alone, and eight received chemotherapy and RT--with a median dose of 30 Gy. The median follow-up time was 5.1 years.nnnRESULTSnA complete response (CR) to RT alone was achieved in 84 of 85 patients. Among CR patients, 14 experienced relapse. Relapse sites were mostly contralateral paired-organ or distant MALT locations and, infrequently, lymph nodes. The crude local control rate with RT was 95.3% (81 of 85 patients). No relapses were observed in patients with stomach or thyroid lymphoma, whereas 14 of 63 patients (22%) experienced relapse in the other sites. The overall 5-year survival rate was 98%, and the disease-free survival rate was 77%. Transformed lymphoma was observed in 14% of patients (two of 14) experiencing relapse.nnnCONCLUSIONnModerate-dose RT achieved excellent local control in localized MALT lymphomas and had curative potential for three fourths of the patients. Gastric and thyroid MALT lymphomas had better outcome, whereas distant failures were common for other sites. Despite relapse, the disease often maintained an indolent course.

Stereotactic Body Radiotherapy for Medically Inoperable Lung Cancer: Prospective, Single-Center Study of 108 Consecutive Patients

PURPOSEnTo present the results of stereotactic body radiotherapy (SBRT) for medically inoperable patients with Stage I non-small-cell lung cancer (NSCLC) and contrast outcomes in patients with and without a pathologic diagnosis.nnnMETHODS AND MATERIALSnBetween December 2004 and October 2008, 108 patients (114 tumors) underwent treatment according to the prospective research ethics board-approved SBRT protocols at our cancer center. Of the 108 patients, 88 (81.5%) had undergone pretreatment whole-body [18F]-fluorodeoxyglucose positron emission tomography/computed tomography. A pathologic diagnosis was unavailable for 33 (28.9%) of the 114 lesions. The SBRT schedules included 48 Gy in 4 fractions or 54-60 Gy in 3 fractions for peripheral lesions and 50-60 Gy in 8-10 fractions for central lesions. Toxicity and radiologic response were assessed at the 3-6-month follow-up visits using conventional criteria.nnnRESULTSnThe mean tumor diameter was 2.4-cm (range, 0.9-5.7). The median follow-up was 19.1 months (range, 1-55.7). The estimated local control rate at 1 and 4 years was 92% (95% confidence interval [CI], 86-97%) and 89% (95% CI, 81-96%). The cause-specific survival rate at 1 and 4 years was 92% (95% CI, 87-98%) and 77% (95% CI, 64-89%), respectively. No statistically significant difference was found in the local, regional, and distant control between patients with and without pathologically confirmed NSCLC. The most common acute toxicity was Grade 1 or 2 fatigue (53 of 108 patients). No toxicities of Grade 4 or greater were identified.nnnCONCLUSIONSnLung SBRT for early-stage NSCLC resulted in excellent local control and cause-specific survival with minimal toxicity. The disease-specific outcomes were comparable for patients with and without a pathologic diagnosis. SBRT can be considered an option for selected patients with proven or presumed early-stage NSCLC.

Decline in tested and self-reported cognitive functioning after prophylactic cranial irradiation for lung cancer: Pooled secondary analysis of radiation therapy oncology group randomized trials 0212 and 0214

PURPOSEnTo assess the impact of prophylactic cranial irradiation (PCI) on self-reported cognitive functioning (SRCF), a functional scale on the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30).nnnMETHODS AND MATERIALSnRadiation Therapy Oncology Group (RTOG) protocol 0214 randomized patients with locally advanced non-small cell lung cancer to PCI or observation; RTOG 0212 randomized patients with limited-disease small cell lung cancer to high- or standard-dose PCI. In both trials, Hopkins Verbal Learning Test (HVLT)-Recall and -Delayed Recall and SRCF were assessed at baseline (after locoregional therapy but before PCI or observation) and at 6 and 12 months. Patients developing brain relapse before follow-up evaluation were excluded. Decline was defined using the reliable change index method and correlated with receipt of PCI versus observation using logistic regression modeling. Fishers exact test correlated decline in SRCF with HVLT decline.nnnRESULTSnOf the eligible patients pooled from RTOG 0212 and RTOG 0214, 410 (93%) receiving PCI and 173 (96%) undergoing observation completed baseline HVLT or EORTC QLQ-C30 testing and were included in this analysis. Prophylactic cranial irradiation was associated with a higher risk of decline in SRCF at 6 months (odds ratio 3.60, 95% confidence interval 2.34-6.37, P<.0001) and 12 months (odds ratio 3.44, 95% confidence interval 1.84-6.44, P<.0001). Decline on HVLT-Recall at 6 and 12 months was also associated with PCI (P=.002 and P=.002, respectively) but was not closely correlated with decline in SRCF at the same time points (P=.05 and P=.86, respectively).nnnCONCLUSIONSnIn lung cancer patients who do not develop brain relapse, PCI is associated with decline in HVLT-tested and self-reported cognitive functioning. Decline in HVLT and decline in SRCF are not closely correlated, suggesting that they may represent distinct elements of the cognitive spectrum.

Induction chemoradiation therapy followed by surgical resection for non-small cell lung cancer (NSCLC) invading the thoracic inlet §

OBJECTIVEnThe role of induction therapy for non-small cell lung cancer (NSCLC) invading the thoracic inlet is unclear. We reviewed our experience with induction chemoradiation followed by surgical resection for NSCLC invading the thoracic inlet.nnnMETHODSnWe performed a retrospective review of 44 consecutive patients with NSCLC invading the thoracic inlet, treated with induction chemoradiation (two cycles of cisplatin and etoposide concurrently with 45Gy of radiation) followed by surgical resection between 1996 and 2007.nnnRESULTSnAll patients underwent chest wall resection (1-5 ribs, mean 3) with resection of the first rib through an anterior (n=15), a posterior (n=18), or a combined approach (n=11). Lobectomy was performed in 40 cases (90%), pneumonectomy in two (5%), and wedge resection in two (5%). Resection of subclavian vessels or portions of vertebrae was performed in five (11%) and 15 (34%) patients, respectively. Hospital mortality was 5% (n=2). R0-resection was achieved in 39 patients (89%). On pathologic examination, 13 patients (30%) showed complete response (pCR) to induction therapy, and 15 (34%) showed minimal microscopic residual disease (90-99% tumor necrosis). The median follow-up was 2 years (range, 2 month-10 years) with an overall cumulative 5-year survival of 59%. Sixteen patients (36%) developed recurrence, which was local in five cases and distant in 11 patients. The 5-year survival in patients with pCR was 90%; 69% in those with minimal residual disease, and 12% in patients with no relevant response (p=0.0005).nnnCONCLUSIONSnResection of NSCLC invading the thoracic inlet can be performed safely after induction chemoradiation therapy. The response rate after induction therapy is a strong predictor of survival.

Induction chemoradiotherapy facilitates radical resection of T4 non-small cell lung cancer invading the spine.

OBJECTIVEnWe evaluated the outcome, long-term results, and factors affecting outcome of induction chemoradiotherapy followed by surgical resection for T4 non-small cell lung cancer invading the spine.nnnMETHODSnRetrospective analysis of 23 consecutive patients undergoing radical vertebral resection for non-small cell lung cancer invading the spine between 1996 and 2007 was performed. In most cases, induction chemoradiotherapy consisted of cisplatin and etoposide followed by 45 Gy of radiation. Surgical resection with vertebrectomy was performed en bloc in either a 1-stage or 2-stage operation. Survival was estimated by Kaplan-Meier techniques. The log-rank comparison was used to compare groups.nnnRESULTSnThere were 13 men and 10 women with a median age of 61 years (range 32-75). Twenty-two patients had induction chemoradiotherapy and 1 had induction chemotherapy alone. Vertebral resections included 6 total vertebrectomies, 15 hemivertebrectomies, and 2 partial vertebrectomies. Complete resection was achieved in 19 (83%) patients. Two (8.7%) patients died postoperatively. Pathologic complete response was observed in 10 (43%) patients. The 3-year survival was 58% (median follow-up, 34 months). Patients who achieved pathologic complete response or near complete response (viable tumor cells < 1%) demonstrated significantly better survival than those who did not (3-year survival, 92% vs 20%; P = .006).nnnCONCLUSIONnHighly selected patients with lung cancer invading the spine can potentially be cured with induction chemoradiation therapy followed by radical en bloc resection of the tumor. A multidisciplinary operative strategy allows a significant chance of achieving complete resection in patients requiring multilevel hemivertebrectomy or total vertebrectomy and an appreciable cure rate.

Chemoradiotherapy for Locoregional Recurrence of Non–Small-Cell Lung Cancer After Surgical Resection: A Retrospective Analysis

BACKGROUNDnEven if non-small-cell lung cancer (NSCLC) is diagnosed early and resected, recurrence is common. Uncertainty exists about the optimal treatment of locoregional recurrence. In fit patients with locoregional recurrence, chemoradiotherapy is sometimes offered, but no data exist about the feasibility and efficacy of this approach. We retrospectively collected data from patients treated this way to assess their outcomes and to identify prognostic factors.nnnPATIENTS AND METHODSnDatabases of The Ottawa Hospital Cancer Centre (TOHCC) (N = 5791) and the Princess Margaret Hospital (PMH) (N = 2225) were screened to identify patients with recurrent NSCLC after curative resection who were offered curative-intent chemoradiotherapy. Selected patients charts were reviewed.nnnRESULTSnThirty patients fit our search criteria. The median disease-free interval was 15 months (2-33 months) and stage at recurrence was mainly T0 (n = 25 [83%]), N2 (n = 25 [83%]), and M0 (n = 29 [97%]). The median radiation dose given at recurrence was 63.5 Gy (26-66 Gy). Chemotherapy included a platinum agent in all cases, mostly a platinum-vinorelbine doublet (n = 14 [47%]), at a median of 3 cycles, (1-6 cycles) 2 of which were concurrent (0-3 cycles). Toxicities were as expected from thoracic chemoradiotherapy, with 7 cases of grade 4 toxicities and no treatment-related deaths. Median follow-up was 22 months (1.5-88 months). Median survival after recurrence was 26.9 months. No prognostic factors were identified.nnnCONCLUSIONnChemoradiotherapy for locoregional recurrent NSCLC is practiced sporadically. This treatment is feasible for highly selected patients, and in our cohort, it allowed for a significantly higher than expected survival. No prognostic factors were identified. Chemoradiotherapy for locoregional NSCLC should be examined in a prospective trial.

Randomized Phase II Study Comparing Prophylactic Cranial Irradiation Alone to Prophylactic Cranial Irradiation and Consolidative Extracranial Irradiation for Extensive-Disease Small Cell Lung Cancer (ED SCLC): NRG Oncology RTOG 0937

Introduction: NRG Oncology RTOG 0937 is a randomized phase II trial evaluating 1‐year overall survival (OS) with prophylactic cranial irradiation (PCI) or PCI plus consolidative radiation therapy (PCI+cRT) to intrathoracic disease and extracranial metastases for extensive‐disease SCLC. Methods: Patients with one to four extracranial metastases were eligible after a complete response or partial response to chemotherapy. Randomization was to PCI or PCI+cRT to the thorax and metastases. Original stratification included partial response versus complete response after chemotherapy and one versus two to four metastases; age younger than 65 years versus 65 years or older was added after an observed imbalance. PCI consisted of 25 Gy in 10 fractions. cRT consisted of 45 Gy in 15 fractions. To detect an improvement in OS from 30% to 45% with a 34% hazard reduction (hazard ratio = 0.66) under a 0.1 type 1 error (one sided) and 80% power, 154 patients were required. Results: A total of 97 patients were randomized between March 2010 and February 2015. Eleven patients were ineligible (nine in the PCI group and two in the PCI+cRT group), leaving 42 randomized to receive PCI and 44 to receive PCI+cRT. At planned interim analysis, the study crossed the futility boundary for OS and was closed before meeting the accrual target. Median follow‐up was 9 months. The 1‐year OS was not different between the groups: 60.1% (95% confidence interval [CI]: 41.2–74.7) for PCI and 50.8% (95% CI: 34.0–65.3) for PCI+cRT (p = 0.21). The 3‐ and 12‐month rates of progression were 53.3% and 79.6% for PCI and 14.5% and 75% for PCI+cRT, respectively. Time to progression favored PCI+cRT (hazard ratio = 0.53, 95% CI: 0.32–0.87, p = 0.01). One patient in each arm had grade 4 therapy‐related toxicity and one had grade 5 therapy‐related pneumonitis with PCI+cRT. Conclusions: OS exceeded predictions for both arms. cRT delayed progression but did not improve 1‐year OS.