Impact of LKB1 status on radiation outcome in patients with stage III non-small-cell lung cancer.

Preclinical studies suggest that loss of LKB1 expression renders cancer cells less responsive to radiation partly through NRF2-mediated upregulation of antioxidant enzymes protecting against radiation-induced DNA damage. Here we investigated the association of an alteration in this pathway with radio-resistance in lung cancer patients. Patients with locally advanced non-small cell lung cancer (LA-NSCLC) who were treated with chemoradiotherapy (CRT) and analyzed for LKB1 expression using semiquantitative immunohistochemistry. Clinical characteristics and expression of LKB1 were analyzed for association with radiotherapy outcomes. We analyzed 74 available tumor specimens from 178 patients. After a median follow-up of 40.7 months, 2-year cumulative incidence of locoregional recurrence (LRR) in patients who had LKB1Low expression was significantly higher than those with LKB1High expression (68.8% vs. 31.3%, P = 0.0001). LKB1Low expression was found significantly associated with a higher incidence of distant metastases (DM) (P = 0.0008), shorter disease-free survival (DFS) (P = 0.006), and worse overall survival (OS) (P = 0.02) compared to LKB1High expression. Moreover, patients with LKB1Low expression showed a significantly higher 2-year cumulative incidence of LRR (77.6% vs. 21%; P = 0.02), higher DM recurrence (P = 0.002), and shorter OS (P < 0.0001) compared with the EGFR-mutant group. For all patients with LKB1Low who had LRR, these recurrences occurred within the field of radiation, in contrast to those with LKB1High expression having both in-field, marginal, and out-of-field failures. LKB1 expression may serve as a potential biomarker for poor outcomes after receiving radiation in LA-NSCLC patients. Further studies to confirm the association and application are warranted.

EUS-guided radiofrequency ablation plus chemotherapy versus chemotherapy alone for pancreatic cancer (ERAP): An observational open-label pilot study.

Background: No study has compared EUS-guided radiofrequency ablation (EUS-RFA) plus systemic chemotherapy (CMT) with CMT alone for unresectable pancreatic ductal adenocarcinoma. Methods: This study compared the results of treatment in patients receiving EUS-RFA plus concomitant CMT (group A; n = 14) with those receiving CMT (group B; n = 14) as a pilot study. Results: From July 2017 to August 2018, 4 and 2 patients from groups A and B, respectively, withdrew from the study because of progression of the disease. In total, 10 and 12 patients from groups A and B, respectively, completed the study. All 30 EUS-RFA procedures were successful. Mean maximal tumor diameter before treatment of group A (n = 10) versus B (n = 12) was 62.2 ± 21.0 versus 50.5 ± 22.0 mm, respectively (P = not significant). After treatment, no statistically significant difference in mean maximal tumor diameter was found between both groups. However, in group B, mean maximal tumor diameter was significantly increased from 50.5 ± 22.0 to 56.3 ± 18.7 mm, respectively (P = 0.017). Tumor necrosis occurred in group A versus B at 10 of 10 (100%) versus 6 of 12 (50%) patients, respectively (P = 0.014). After treatment, group A patients could reduce the mean narcotic pain drug dosage at 26.5 mg of morphine equivalent per day (from 63.6 to 37.1 mg, P = 0.022), whereas group B patients could not reduce the dosage of pain-controlled medication. No statistically significant difference in 6-month mortality rate was found. In group A, 1 procedure-related nonsevere adverse event (n = 1 of 30 [3.3%]) occurred in 1 patient (n = 1 of 14 [7.1%]). Conclusions: In this study, the mean tumor diameter of group B was significantly increased after the treatment. Group A had a significantly higher rate of necrosis of tumor and required less narcotic.

Postoperative radiotherapy timing, molecular subgroups and treatment outcomes of Thai pediatric patients with medulloblastoma.

INTRODUCTION: Medulloblastoma (MB) is the most common childhood malignant brain tumor worldwide. Recently, molecular classification was established and started to play a role in the management of MB; however, studies involving molecular defined MB in Southeast Asia have been limited. We aimed to describe, and correlate clinical characteristics and molecular subgroups with therapeutic outcomes of Thai pediatric patients with MB. MATERIALS AND METHODS: Pediatric MB patients treated at King Chulalongkorn Memorial Hospital in Thailand from 2006 to 2018 were recruited. Patients were classified by clinical characteristics into standard- and high-risk groups, which determined treatment regimen. Retrospectively, available tumor tissues were classified into 3 molecular subgroups using immunohistochemistry: 1) WNT, 2) SHH, and 3) non-WNT/non-SHH. The primary outcome was 5-year overall survival (OS). Risk factors associated with OS were analyzed using cox regression analysis. RESULTS: Fifty-three Thai pediatric patients with MB were enrolled. The median follow-up time was 60 months. The 5-year OS for all patients, and patients with standard-risk and high-risk were 74.2%, 76.3% and 71.4%, respectively. Tumor tissues of 24 patients were available, of which 23 could be molecularly classified. Two, one and 20 were in the WNT, SHH and non-WNT/non-SHH subtypes with 5-year OS of 100%, 100% and 78.9%, respectively. Using multivariate analysis, the interval of more than 8 weeks between surgery and radiotherapy was significantly correlated with a decrease in the 5-year OS. CONCLUSION: Interval between surgery and radiotherapy within 8 weeks was associated with good therapeutic outcomes among Thai pediatric patients with MB. Simplified molecular subtyping combined with clinical characteristics is practical in risk classification of patients with MB in institutes with limited resources.

KRAS Mutation in Pediatric Intracranial Germ Cell Tumors.

BACKGROUND: Intracranial germ cell tumors (IGCTs) are rare, highly curable neoplasms. KRAS is a gene in the KIT/RAS signaling pathway, and KRAS mutations have been reported in patients diagnosed with IGCTs. OBJECTIVES: To describe the clinicopathologic and molecular features of KRAS mutation and the treatment outcome of children diagnosed with IGCTs. METHODS: Patients diagnosed with IGCTs at the Department of Pediatrics, King Chulalongkorn Memorial Hospital from 2007 to 2016 were retrospectively reviewed. DNA was extracted from formalin-fixed, paraffin-embedded tissue and used for molecular study. Mutations in codons 12, 13, and 61 of the KRAS gene were detected using the cobas® KRAS mutation test and pyrosequencing. RESULTS: Eighteen patients were diagnosed with IGCTs (11 males and 7 females): nine with germinomas and nine with non-germinomatous GCTs (NGGCTs). The age range of the patients was 5-14 years (median 10.5 years). Elevated markers were revealed in approximately 25% of the patients. Four patients (two with germinomas and two with NGGCTs) had leptomeningeal involvement. All patients underwent tumor biopsy and received neoadjuvant chemotherapy. Radiotherapy was administered in 16 patients, and craniospinal radiation was administered only in patients with leptomeningeal metastasis. With a median follow-up of 26 months, overall survival was 88.9% in the patients with germinomas and 37% in the patients with NGGCTs. Mutation of the KRAS gene was detected using pyrosequencing in one patient. The mutation located at codon 61, with frequency 38.3% units, nucleotide substitution CAA > CTA, and amino acid substitution, was Q61L. The patient carrying the mutant gene was diagnosed with germinoma with cerebrospinal fluid metastasis and eventually died from treatment-related toxicity. CONCLUSION: Our study revealed the treatment outcomes of IGCTs in Thai children. The metastatic germinoma patient with KRAS codon 61 mutation had a poor outcome, supporting that Q61L has a clinical correlation with IGCTs.

Long-term oncological outcomes of hypofractionated versus conventional fractionated whole breast irradiation with simultaneous integrated boost in early-stage breast cancer.

PURPOSE: For patients with early breast cancer who undergo breast-conserving surgery, adjuvant whole breast irradiation (WBI) with simultaneous integrated boost (SIB) results in lower radiotherapy fractions. Published studies have shown that both conventional fraction with SIB (C-SIB) and hypofractionation with SIB (H-SIB) seem to be safe and feasible. In this study, we sought to compare the oncologic outcomes between C-SIB and H-SIB in early-stage breast cancer. MATERIALS AND METHODS: Stage I-II breast cancer patients who received adjuvant WBI with SIB between January 2008 and December 2017 were retrospectively reviewed. The radiation dose in the C-SIB group was 50 Gy and 65 Gy in 25 daily fractions, while in the H-SIB group, it was 43.2 Gy and 52.8 Gy in 16 daily fractions to the whole breast and tumor bed, respectively. RESULTS: A total of 188 patients, 103 in the C-SIB group and 85 in the H-SIB group, were included. With a median follow-up time of 87 months, 7-year locoregional control of C-SIB was comparable to H-SIB (95.8% vs. 97.4%, p = 0.964). The 7-year distant metastasis-free survival rates of C-SIB and H-SIB were 89.9% and 95.9% (p = 0.111), while the 7-year disease-free survival rates were 84.2% and 95.4%, respectively (p = 0.176). In multivariate analysis, there was no significant prognostic factor associated with better overall survival. CONCLUSION: H-SIB provided comparable locoregional control to C-SIB. With the advantage of a shorter radiotherapy course, H-SIB could be a favorable option for WBI in early-stage breast cancer.

Dosimetric evaluation of photons versus protons in postmastectomy planning for ultrahypofractionated breast radiotherapy.

BACKGROUND: Ultrahypofractionation can shorten the irradiation period. This study is the first dosimetric investigation comparing ultrahypofractionation using volumetric arc radiation therapy (VMAT) and intensity-modulated proton radiation therapy (IMPT) techniques in postmastectomy treatment planning. MATERIALS AND METHODS: Twenty postmastectomy patients (10-left and 10-right sided) were replanned with both VMAT and IMPT techniques. There were four scenarios: left chest wall, left chest wall including regional nodes, right chest wall, and right chest wall including regional nodes. The prescribed dose was 26 Gy(RBE) in 5 fractions. For VMAT, a 1-cm bolus was added for 2 in 5 fractions. For IMPT, robust optimization was performed on the CTV structure with a 3-mm setup uncertainty and a 3.5% range uncertainty. This study aimed to compare the dosimetric parameters of the PTV, ipsilateral lung, contralateral lung, heart, skin, esophageal, and thyroid doses. RESULTS: The PTV-D95 was kept above 24.7 Gy(RBE) in both VMAT and IMPT plans. The ipsilateral lung mean dose of the IMPT plans was comparable to that of the VMAT plans. In three of four scenarios, the V5 of the ipsilateral lung in IMPT plans was lower than in VMAT plans. The Dmean and V5 of heart dose were reduced by a factor of 4 in the IMPT plans of the left side. For the right side, the Dmean of the heart was less than 1 Gy(RBE) for IMPT, while the VMAT delivered approximately 3 Gy(RBE). The IMPT plans showed a significantly higher skin dose owing to the lack of a skin-sparing effect in the proton beam. The IMPT plans provided lower esophageal and thyroid mean dose. CONCLUSION: Despite the higher skin dose with the proton plan, IMPT significantly reduced the dose to adjacent organs at risk, which might translate into the reduction of late toxicities when compared with the photon plan.

Long-term results of hypofractionation with concomitant boost in patients with early breast cancer: A prospective study.

AIM: To report the long-term local control and survival of patients with early breast cancer who had hypofractionated whole breast irradiation with concomitant boost (Hypo-CB). METHODS AND MATERIALS: Between October 2009 and June 2010, 73 patients with early breast cancer (T1-3N0-1M0) who underwent breast conserving surgery were enrolled into the study. Thirty-six of these participants received 50 Gy of conventional irradiation in 25 fractions over 5 weeks to the whole breast with a sequential boost to the tumor bed with 10-16 Gy in 5-8 fractions (Conv-SEQ). The other 37 participants received a hypofractionated dose of 43.2 Gy in 16 fractions with an additional daily concomitant boost (CB) of 0.6 Gy over 3 weeks (Hypo-CB). RESULTS: At a median follow-up time of 123 months, ipsilateral local recurrence (ILR) was found in 3 participants, 1 of whom was in the hypofractionated group. All 3 ILR were true local recurrence (TR). There were no significant differences in the 10-year disease free survival (DFS) and 10-year overall survival rates (OS) between the conventional and hypofractionated groups (93.9% vs. 94.4%, p = 0.96 and 91.9% vs. 91.6%, p = 0.792, respectively). CONCLUSION: This study showed that the effectiveness, DFS and OS were comparable between hypofractionated whole breast irradiation with a CB and the conventional irradiation with a sequential boost.

Observed-to-expected incidence ratios of second malignant neoplasms after radiation therapy for medulloblastoma: A Surveillance, Epidemiology, and End Results analysis.

BACKGROUND: The authors analyzed the incidence and types of second malignant neoplasms (SMNs) in patients treated for medulloblastoma. METHODS: The authors compared the incidence of SMNs after radiotherapy (RT) for medulloblastoma in patients treated in 1973-2014 with the incidence in the general population with the multiple primary-standardized incidence ratio function of Surveillance, Epidemiology, and End Results 9. Observed-to-expected incidence (O/E) ratios and 95% confidence intervals (CIs) were reported for the entire cohort and by disease site according to age at diagnosis, treatment era, and receipt of chemotherapy. P values < .05 were considered statistically significant. RESULTS: Of the 1294 patients with medulloblastoma who received RT, 68 developed 75 SMNs. The O/E ratio for SMNs among all patients was 4.49 (95% CI, 3.53-5.62; P < .05). The site at highest risk was the central nervous system (CNS; O/E, 40.62; 95% CI, 25.46-61.51), which was followed by the endocrine system (O/E, 15.95; 95% CI, 9.12-25.91), bone (O/E, 14.45; 95% CI, 1.75-52.21), soft tissues (O/E, 9.01; 95% CI, 1.09-32.56), the digestive system (O/E, 5.03; 95% CI, 2.51-9.00), and the lymphatic/hematopoietic system (O/E, 3.37; 95% CI, 1.35-6.94). The O/E ratio was higher for patients given chemotherapy and RT (O/E, 5.52; 95% CI, 3.75-7.83) than for those given RT only (O/E, 3.96; 95% CI, 2.88-5.32). CONCLUSIONS: Patients with medulloblastoma are at elevated risk for SMNs in comparison with the general population. Variations in O/E for SMNs by organ systems were found for treatment modality, age at diagnosis, and time of diagnosis. The most common site, the CNS, was involved more often in younger patients and those given chemotherapy with RT.

Flattening filter free stereotactic body radiation therapy for lung tumors: outcomes and predictive factors.

BACKGROUND: Stereotactic body radiation therapy (SBRT) using flattening filter free (FFF) has been commonly used, however, its outcomes and predictive factors in lung tumors are limiting. Thus, we aim to assess the clinical outcomes of this approach and identify factors associated with outcomes in patients with early stage non-small cell lung cancer (NSCLC) and oligometastatic/oligoprogressive lung tumor (OLT). METHODS: Patients who underwent lung SBRT with FFF were retrospectively reviewed. All patients were delivered using volumetric modulated arc therapy (VMAT) technique. The primary outcome was local control (LC). The secondary outcomes were overall survival (OS) and toxicities. We assessed the association between LC and various factors in OLT. RESULTS: From February 2014 to July 2019, ninety-four patients and 129 lesions with median follow-up time of 30 months were included in the analysis. Twenty-six patients with 26 lesions were early NSCLC, while 68 patients with 103 lesions were OLT, 41.7% of which were from colorectal cancers (CRC) and 18.5% were from primary lung cancers. Two-year LC was 88.9% and 85.7% for early NSCLC and OLT, respectively. Two-year OS was significantly higher for early NSCLC than OLT (83.3% vs. 68.7%, P=0.035). In the multivariate analysis for OLT, CRC origin (hazard ratio, HR 10.59, 95% CI: 2.29-48.95, P=0.003) and gross tumor volume (GTV) mean BED10 ≤147 Gy (HR 5.16, 95% CI: 1.13-23.59, P=0.034) were significantly associated with higher local failure (LF). Most of the acute grade 1-2 toxicities were radiation pneumonitis (26.5%). No grade 3-5 event was observed. CONCLUSIONS: This study confirmed the clinical efficacy and safety of lung SBRT using FFF-technique. Our findings support the role of using a high BED10 regimen to achieve good LC for OLT and the potential role for dose escalation for primary CRC.

Results of intraoperative radiotherapy given as a boost after breast conserving-surgery.

BACKGROUND: Whole breast irradiation after breast-conserving surgery (BCS) with an external beam boost of 10-16 Gy is currently the standard treatment in breast cancer. Various modalities have been used for tumor bed boost irradiation. This study aimed to evaluate the local recurrence rate, overall survival rate (OSR), toxicity and cosmetic outcome of intraoperative radiotherapy (IORT) as a boost followed by whole breast irradiation in patients who received BCS. METHODS: This is a retrospective study. Between December 2009 and March 2017, 81 patients who underwent BCS with IORT as a boost were enrolled in this study. For IORT, a single dose of 20 Gy was delivered using a 30-50 kV photon beam, intraoperatively. All patients received whole breast radiation therapy (WBRT) of 42.5-50 Gy over 4-5 weeks. The primary endpoint was a 3-year local recurrence rate. Secondary endpoints included the OSR, toxicity and cosmetic outcome at 6 months after radiation treatment. RESULTS: At a median follow-up of 43 months, ipsilateral local recurrence was observed in one of the 81 patients (1.2%) which occurred in the same quadrant of the breast index. The 3-year OSR was 89.8%. Treatment was well-tolerated with no grade 3-4 acute and late toxicity, and 87% of patients were recorded as excellent-good cosmesis. CONCLUSIONS: The use of BCS with IORT as a boost resulted in a low local recurrence rate and excellent cosmetic outcome in early breast cancer. Thus, IORT as a boost could be considered as an alternative to an external beam boost. Prospective studies are needed to confirm this data.

The effect of deep inspiration breath-hold technique on left anterior descending coronary artery and heart dose in left breast irradiation.

PURPOSE: To determine the effect of the deep inspiration breath-hold (DIBH) technique on left anterior descending coronary artery (LAD) region and heart dose in left breast cancer irradiation. MATERIALS AND METHODS: Twenty-five left breast cancer patients who previously received breast-conserving surgery underwent computed tomography (CT) simulation with both free-breathing (FB) and DIBH techniques and four radiation treatment plans. The plan comprised the following with both the FB and DIBH techniques: whole breast (WB), and WB with internal mammary lymph nodes (WB+IMNs). The prescription dose was 50 Gy in 25 fractions. The doses to the LAD region, heart and lungs were compared. Moreover, in-field maximum heart distance (maxHD) and breast volume were analyzed for correlations with the mean heart dose (MHD). RESULTS: In the WB plan with DIBH vs. FB techniques, the mean radiation doses to the LAD region, MHD, and the left lung V20 were 11.48 Gy vs. 19.84 Gy (p < 0.0001), 2.95 Gy vs. 5.38 Gy (p < 0.0001), and 19.72% vs. 22.73% (p = 0.0045), respectively. In the WB+IMNs plan, the corresponding values were 23.88 Gy vs. 31.98 Gy (p < 0.0001), 6.43 Gy vs. 10.24 Gy (p < 0.0001), and 29.31% vs. 32.1% (p = 0.0009), respectively. MHD correlated with maxHD (r = 0.925) and breast volume (r = 0.6). CONCLUSION: The use of the DIBH technique in left breast cancer irradiation effectively reduces the radiation doses to the LAD region, heart and lungs. MHD is associated with maxHD and breast size.

Development of second primary tumors and outcomes in medulloblastoma by treatment modality: A Surveillance, Epidemiology, and End Results analysis.

BACKGROUND: As treatment modalities for medulloblastoma have developed and overall survival (OS) has improved, there are relatively limited data on the impact of long-term effects such as risk of second primary tumors (SPT). To address the knowledge gap, we analyzed factors associated with the risk of SPT and OS by treatment modality for medulloblastoma. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER)-18 database for patients diagnosed with medulloblastoma in 1973-2014. Patients were then grouped by age, gender, race, geographic region, histology, adjuvant treatment (no radiation [RT] and no chemotherapy [CT], RT and CT, RT alone, or CT alone), era of diagnosis (1973-1994 or 1995-2014), and survival time. Cumulative incidence, factors associated with SPT and OS were analyzed. RESULTS: Of 2271 patients, 146 developed SPT, of which 42 were benign. The incidence of SPT was 3.1% and 4.9% at 10 and 15 years, respectively. The incidence of SPT was 3.1% with RT + CT versus 3.7% with RT alone at 10 years. The most common site for an SPT was the central nervous system. Female gender (P = 0.01) and longer OS of ≥21 years (P < 0.01) were associated with higher risk of SPT. RT + CT led to better OS than RT only (66.1% and 61.4% vs 55.6% and 49.7% at 10 and 15 years) (P < 0.01). CONCLUSIONS: Medulloblastoma patients have a relatively low risk of SPT at 10 years with treatment. Use of RT + CT led to better OS with no statistical difference in SPT compared with the RT alone.

An improved method for analyzing and reporting patterns of in-field recurrence after stereotactic ablative radiotherapy in early-stage non-small cell lung cancer.

INTRODUCTION: Patterns of local, regional, and distant failure after stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer (NSCLC) have been widely reported. However, reliable methods for analyzing causes of local failure are lacking. We describe a method for analyzing and reporting patterns of in-field recurrence after SABR, incorporating dosimetric parameters from initial treatment plan as well as geometric information from diagnostic images at recurrence. MATERIAL AND METHODS: Diagnostic CT images at recurrence were registered with initial treatment planning images and radiation dose by deformable image registration. Recurrent gross tumor volume (rGTV) and centroid (geometric center of rGTV) were delineated. In-field failure was classified as centroids originating within the original planning target volume. Dose-volume histograms for each rGTV were used to further classify in-field recurrences as central high-dose (dose to 95% of rGTV [rGTVD95%] ≥95% of dose prescribed to PTV) or peripheral high-dose (rGTVD95% <95% of dose prescribed to PTV). RESULTS: 634 patients received SABR from 2004 to 2014 with 48 local recurrences. 35 of these had evaluable images with 16 in-field recurrences: 9 central high-dose, 6 peripheral high-dose, and 1 had both. Time to and volume of recurrence were not statistically different between central versus peripheral high-dose recurrences. However mean rGTV dose, mean centroid dose, and rGTVD95% were higher for central versus peripheral high-dose recurrences. CONCLUSION: We report a standardized method for analysis and classification of in-field recurrence after SABR. There were more central as opposed to peripheral high-dose recurrences, suggesting biological rather than technical issues underlying majority of in-field failures.

A predictive model of radiation-related fibrosis based on the radiomic features of magnetic resonance imaging and computed tomography.

BACKGROUND: To establish a predictive model for the fibrotic level of neck muscles after radiotherapy by using radiomic features extracted from the magnetic resonance imaging (MRI) before and after radiotherapy and planning computed tomography (CT) in nasopharyngeal carcinoma patients. METHODS: A total of one hundred and eighty-six patients were finally enrolled in this study. According to the specific standard, all patients were divided into three different fibrosis groups. Regions of interests (ROI), including sternocleidomastoids (SCMs), trapezius (T), levator scapulae (LS), and scalenus muscles (S), were delineated manually and used for features extraction on IBEX. XGBoost, a machine learning algorithm, was used for the establishment of the prediction model. First, the patients were divided into training cohort (80%) and testing cohort (20%) randomly. Then the image features of CT or delta changes calculated from pre- and post-radiotherapy MRI images on each cohort constituted training and testing datasets. Then, based on the training dataset, a well-trained prediction model was produced. We used five-fold cross-validation to validate the predictive models. Afterward, the model performance was assessed on the 'testing' set and reported in terms of area under the receiver operating characteristic curve (AUC) under five scenarios: (I) only T1 sequence, (II) only T2 sequence, (III) only T1 post-contrast (T1 + C) sequence, (IV) Combination of all MRI sequences, (V) only CT. RESULTS: Most of the patients enrolled are male (73.1%), mean age was 47 years, receiving concurrent chemo-radiotherapy as the primary treatment (90.9%). By the end of the final follow-up, most of the patients were rated as mild fibrosis (60.8%). We found the prediction model based on the CT image features outperform all MRI features with an AUC of 0.69 and accuracy of 0.65. Contrarily, the model based on features from all MRI sequence showed lower AUC less than 0.5 and lower accuracy less than 0.6. CONCLUSIONS: The prediction model based on CT radiomics features has better performance in the prediction of the grade of post-radiotherapy neck fibrosis. This might help guide radiotherapy treatment planning to achieve a better quality of life.

Clinical and Dosimetric Factors Predicting Grade ≥2 Radiation Pneumonitis After Postoperative Radiotherapy for Patients With Non-Small Cell Lung Carcinoma.

PURPOSE: To identify clinical and dosimetric factors that would predict grade ≥2 radiation pneumonitis (RP) for patients undergoing postoperative radiation therapy (PORT) for non-small cell lung cancer (NSCLC); and to use the factors identified to generate a predictive model to quantify risk of RP in such patients. METHODS AND MATERIALS: We retrospectively reviewed radiation therapy, radiographic, and clinical data from 199 patients who had received PORT, with or without chemotherapy, for NSCLC. Potential associations between dosimetric and clinical factors and RP were evaluated in univariate and multivariate Cox regression hazard models and competing risk analysis. Kaplan-Meier analysis was used to estimate overall survival and the cumulative incidence of RP, and receiver operating characteristic curve analysis to identify cutpoints for variables found to influence RP risk. The endpoint was grade ≥2 RP (symptomatic, requiring steroids or limiting instrumental activities of daily living). RESULTS: Thirty-seven patients (19%) developed grade ≥2 RP. Patient-related factors, type of surgery or chemotherapy, and radiation therapy-related factors were not associated with grade ≥2 RP; only lung V10 > 30% and lung V20 > 20% predicted grade ≥2 RP. Risk groupings were as follows: high risk, V10 > 30% and V20 > 20% (24 of 72 patients, 33%); intermediate risk, V10 > 30% and V20 ≤ 20% or V10 ≤ 30% and V20 > 20% (6 of 26 patients, 23%); and low risk, V10 ≤ 30% and V20 ≤ 20% (6 of 101 patients, 6%) (P < .0001). In a subgroup analysis of patients who had had lobectomy, corresponding incidences of RP were as follows: high risk, 20 of 59 (34%); intermediate risk, 5 of 22 (23%); and low risk, 6 of 70 (9%) (P = .001). CONCLUSIONS: The lung dose-volume variables V10 and V20 predicted risk of grade ≥2 RP among patients who underwent PORT for NSCLC.

Phase 2 Study of Stereotactic Body Radiation Therapy and Stereotactic Body Proton Therapy for High-Risk, Medically Inoperable, Early-Stage Non-Small Cell Lung Cancer.

PURPOSE: To report the feasibility of conducting a randomized study to compare the toxicity and efficacy of stereotactic body radiation therapy (SBRT) versus stereotactic body proton therapy (SBPT) for high-risk, medically inoperable, early-stage non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with medically inoperable NSCLC with high-risk features (centrally located or <5 cm T3 tumor or isolated lung parenchymal recurrences) were randomly assigned to SBRT or SBPT. Radiation dose was 50 Gy(relative biological effectiveness [RBE]) in 4 12.5-Gy(RBE) fractions prescribed to the planning target volume. Stereotactic body radiation therapy was given using 3-dimensional conformal radiation therapy or intensity modulated radiation therapy, and SBPT was given using passive scattering. Consistency in patient setup was ensured with on-board cone beam computed tomography for the SBRT group and with orthogonal X rays for the SBPT group. RESULTS: The study closed early owing to poor accrual, largely because of insurance coverage and lack of volumetric imaging in the SBPT group. Ultimately, 21 patients were enrolled, and 19 patients who received 50 Gy in 4 fractions were included for analysis (9 SBRT, 10 SBPT). At a median follow-up time of 32 months, median overall survival time was 28 months in the SBRT group and not reached in the SBPT group. Three-year overall survival was 27.8% and 90%, 3-year local control was 87.5% (8 of 9) and 90.0% (9 of 10), and 3-year regional control was 47.6% (5 of 9) and 90% (9 of 10) in the SBRT and SBPT groups, respectively. One patient in the SBPT group developed grade 3 skin fibrosis. No patients experienced grade 4/5 toxicity. CONCLUSION: Poor accrual, due to lack of volumetric imaging and insurance coverage for proton therapy, led to early closure of the trial and precluded accurate assessment of efficacy and toxicity. Comparable maturity of 2 radiation therapy modalities, particularly on-board imaging, and better insurance coverage for SBPT should be considered for future studies.