S. Apisarnthanarax

A moving target: Image guidance for stereotactic body radiation therapy for early-stage non-small cell lung cancer

PURPOSEnPrecise patient positioning is critical due to the large fractional doses and small treatment margins employed for thoracic stereotactic body radiation therapy (SBRT). The goals of this study were to evaluate the following: (1) the accuracy of kilovoltage x-ray (kV x-ray) matching to bony anatomy for pretreatment positioning; (2) the magnitude of intrafraction tumor motion; and (3) whether treatment or patient characteristics correlate with intrafraction motion.nnnMETHODS AND MATERIALSnEighty-seven patients with lung cancer were treated with SBRT. Patients were positioned with orthogonal kV x-rays matched to bony anatomy followed by cone-beam computed tomography (CBCT), with matching of the CBCT-visualized tumor to the internal gross target volume obtained from a 4-dimensional CT simulation data set. Patients underwent a posttreatment CBCT to assess the magnitude of intrafraction motion.nnnRESULTSnThe mean CBCT-based shifts after initial patient positioning using kV x-rays were 2.2 mm in the vertical axis, 1.8 mm in the longitudinal axis, and 1.6 mm in the lateral axis (n = 335). The percentage of shifts greater than 3 mm and 5 mm represented 39% and 17%, respectively, of all fractions delivered. The mean CBCT-based shifts after treatment were 1.6 mm vertically, 1.5 mm longitudinally, and 1.1 mm laterally (n = 343). Twenty-seven percent and 10% of shifts were greater than 3 mm and 5 mm, respectively. Univariate and multivariable analysis demonstrated a significant association between intrafraction motion with weight and pulmonary function.nnnCONCLUSIONSnKilovoltage x-ray matching to bony anatomy is inadequate for accurate positioning when a conventional 3-5 mm margin is employed prior to lung SBRT. Given the treatment techniques used in this study, CBCT image guidance with a 5-mm planning target volume margin is recommended. Further work is required to find determinants of interfraction and intrafraction motion that may help guide the individualized application of planning target volume margins.

Impact of PET staging in limited-stage small-cell lung cancer

Introduction: Although positron emission tomography computed tomography (PET-CT) has been widely used for small-cell lung cancer (SCLC) staging, no study has examined the clinical impact of PET staging in limited-stage (LS) SCLC. Methods: We identified patients with LS-SCLC treated definitively with concurrent chemoradiation. Outcomes were assessed using the Kaplan–Meier approach, Cox regression, and competing risks method. Results: We treated 54 consecutive LS-SCLC patients with concurrent chemoradiation from January 2002 to August 2010. Forty underwent PET, 14 did not, and all underwent thoracoabdominopelvic CT and magnetic resonance imaging neuroimaging. Most patient characteristics were balanced between the comparison groups, including age, race, sex, bone scanning, median dosage, and performance status. More number of PET-staged patients presented with nodal metastases (p = 0.05). Median follow-up was similar for PET-staged and non–PET-staged patients (p = 0.59). Median overall survival from diagnosis in PET-staged patients was 32 versus 17 months in patients staged without PET (p = 0.03), and 3-year survival was 47% versus 19%. Median time-to-distant failure was 29 versus 12 months (p = 0.04); median time-to-local failure was not reached versus 16 months (p = 0.04). On multivariable analysis, PET staging (odds ratio [OR] = 0.24; p = 0.04), performance status (OR = 1.89; p = 0.05), and N-stage (OR = 4.94; p < 0.01) were associated with survival. Conclusion: LS-SCLC patients staged with PET exhibited improved disease control and survival when compared with non–PET-staged LS-SCLC patients. Improved staging accuracy and better identification of intrathoracic disease may explain these findings, underscoring the value of PET-CT in these patients.

Brachial plexopathy in apical non-small cell lung cancer treated with definitive radiation: Dosimetric analysis and clinical implications

PURPOSEnData are limited on the clinical significance of brachial plexopathy in patients with apical non-small cell lung cancers (NSCLC) treated with definitive radiation therapy. We report the rates of radiation-induced brachial plexopathy (RIBP) and tumor-related brachial plexopathy (TRBP) and associated dosimetric parameters in apical NSCLC patients.nnnMETHODS AND MATERIALSnCharts of NSCLC patients with primary upper lobe or superiorly located nodal disease who received ≥50 Gy of definitive conventionally fractionated radiation or chemoradiation were retrospectively reviewed for evidence of brachial plexopathy and categorized as RIBP, TRBP, or trauma-related. Dosimetric data were gathered on ipsilateral brachial plexuses (IBP) contoured according to Radiation Therapy Oncology Group atlas guidelines.nnnRESULTSnEighty patients were identified with a median follow-up and survival time of 17.2 and 17.7 months, respectively. The median prescribed dose was 66.6 Gy (range, 50.4-84.0), and 71% of patients received concurrent chemotherapy. RIBP occurred in 5 patients with an estimated 3-year rate of 12% when accounting for competing risk of death. Seven patients developed TRBP (estimated 3-year rate of 13%), comprising 24% of patients who developed locoregional failures. Grade 3 brachial plexopathy was more common in patients who experienced TRBP than RIBP (57% vs 20%). No patient who received ≤78 Gy to the IBP developed RIBP. On multivariable competing risk analysis, IBP V76 receiving ≥1 cc, and primary tumor failure had the highest hazard ratios for developing RIBP and TRBP, respectively.nnnCONCLUSIONSnRIBP is a relatively uncommon complication in patients with apical NSCLC tumors receiving definitive doses of radiation, while patients who develop primary tumor failures are at high risk for developing morbid TRBP. These findings suggest that the importance of primary tumor control with adequate doses of radiation outweigh the risk of RIBP in this population of patients.

Concomitant Radiotherapy and Chemotherapy for High-Risk Nonmelanoma Skin Carcinomas of the Head and Neck

Background. To report on the use and feasibility of a multimodality approach using concomitant radiotherapy and chemotherapy in patients with high-risk nonmelanoma skin carcinoma (NMSC) of the head and neck. Methods. Records of patients with NMSC of the head and neck who received concomitant CRT at the University of North Carolina between 2001 and 2007 were reviewed. Results. Fifteen identified patients had at least one of the following high-risk factors: T4 disease (93%), unresectability (60%), regional nodal involvement (40%), and/or recurrence (47%). Ten patients were treated in the definitive setting and five in the postoperative setting. Platinum based chemotherapy was given in 14 (93%) patients. Ten of fifteen (67%) patients completed all planned chemotherapy treatments, and thirteen patients (87%) completed at least 80% of planned chemotherapy. Mild radiation dermatitis occurred in all patients and reached grade 3 in 13% of patients. No patients experienced grade 4 or 5 toxicity. With a median followup of 31 months in surviving patients, the 2-year actuarial locoregional control and relapse-free survival were 79% and 49%, respectively. Conclusions. Definitive or postoperative chemoradiotherapy for patients with locally advanced or regionally metastasized NMSC of the head and neck appears feasible with acceptable toxicities and favorable locoregional control.

Definitive dose thoracic radiation therapy in oligometastatic non-small cell lung cancer: A hypothesis-generating study

PURPOSEnA subset of patients with minimal extrathoracic disease may benefit from aggressive primary tumor treatment. We report comparative outcomes in oligometastatic non-small cell lung cancer (NSCLC) treated with and without definitive, conventionally fractionated thoracic radiation therapy.nnnMETHODS AND MATERIALSnWe identified consecutive patients with stage IV NSCLC who had an Eastern Cooperative Oncology Group performance status ≤2 and ≤4 total sites of metastatic disease and who had been prescribed ≥50 Gy of thoracic radiation.nnnRESULTSnTwenty-nine patients with oligometastatic NSCLC were identified between January 2004 and August 2010. Median survival was 22 months from diagnosis. Four patients (14%) experienced pneumonitis greater than or equal to grade 3; 6 (21%) had esophagitis greater than or equal to grade 3. Local control was associated with improved survival (P = .02). In matched subset analysis, median survival was 9 months (P < .01) in patients who received chemotherapy alone. Median time to local failure was 18 versus 6 months (P = .01). On multivariable analysis, radiation (P < .01; odds ratio [OR], 0.33), fewer metastases (P < .01; OR, 2.14), and female sex (P < .01; OR, 0.41) were associated with improved survival.nnnCONCLUSIONSnDefinitive dose radiation therapy may improve survival in a select subset of patients with minimal extrathoracic disease in whom local progression is of primary concern. Prospective trials are needed to further evaluate the role of local control in oligometastatic NSCLC.

Applicability of randomized trials in radiation oncology to standard clinical practice.

Randomized controlled trials (RCTs) are commonly used to inform clinical practice; however, it is unclear how generalizable RCT data are to patients in routine clinical practice. The authors of this report assessed the availability and applicability of randomized evidence guiding medical decisions in a cohort of patients who were evaluated for consideration of definitive management in a radiation oncology clinic.

Proton Reirradiation of Recurrent Rectal Cancer: Dosimetric Comparison, Toxicities, and Preliminary Outcomes

Abstract Purpose: Locally advanced rectal adenocarcinoma is effectively treated with chemoradiation and surgery; however, 10 to 25% of patients locally recur within or near a previously irradiated field. Proton radiation therapy (PRT) is ideally suited to the problem of reirradiation for locally recurrent rectal cancer (LRRC). Patients and Methods: Seven patients with LRRC in or near prior radiation fields were enrolled on this prospective study from March 2010 to February 2011. All patients underwent positron emission tomography (PET)/computed tomography (CT) simulation and were stratified by low volume (clinical target volume 250 cm3, n=3). Primary endpoints were feasibility and acute toxicity (within 90 days from PRT initiation). Dosimetry was compared using the Wilcoxon signed-rank test. Tumor response was defined according to PERCIST criteria. Results: Median follow-up was 14 months (4.9–22.6). Median dose of prior RT was 5040 cGy. Mean PRT dose was 6120 cGy (RBE) (rang...

The impact of radiation therapy sequencing on survival and cardiopulmonary mortality in the combined modality treatment of patients with esophageal cancer.

The addition of chemoradiation (CRT) to surgery has been shown to improve survival in patients with esophageal cancer. In the current study, the authors determined whether the sequencing of CRT has an effect on survival and cardiopulmonary mortality in patients with esophageal cancer.

Predicting Outcomes in Locally-Advanced Rectal Cancer Using Pretreatment FDG-PET Imaging

of axillary and extra-axillary metastases identified by FDG PET/CT in patients scheduled for neoadjuvant chemotherapy, and how often this information could change post-operative radiation planning. Materials/Methods: We performed a retrospective analysis of 38 patients with breast cancer scheduled for neoadjuvant chemotherapy between January 2011 and July 2012. 10 patients were clinical stage II, 26 clinical stage III, 2 clinical stage IV. All patients had a FDG PET/CT within 1 month of diagnosis. 28/32 patients had pathologic confirmation of ipsilateral axillary lymph nodes. We identified the incidence of positive axillary lymph nodes and extra axillary metastases, correlated this with stage, and identified how often this could change radiation planning. Results: Axillary lymph nodes were positive in 32/38 patients (84.2%); 5/ 10 (50%) stage II, 25/26 (96.2%) stage III, 2/2 (100%) stage IV. 28/32 (87.5%) of patients with PET positive axillary lymph nodes had pathologic confirmation. 16/38 patients had extra-axillary metastases. These were identified in 14/26 stage III patients (53.8%) and 2/2 stage IV patients (100%). Sites of extra-axillary PET positive metastases were: subpectoral 11/38 (28.9%), internal mammary chain (IMC) 6/38 (15.8%), supraclavicular 2/38 (5.3%), subclavian 1/38 (2.6%), mediastinal lymph node 1/38 (2.6%), and pulmonary nodule 1/38 (2.6%). One patient with positive IMC nodes did not have positive axillary nodes. In all other cases (15/16) patients with extra axillary metastases had axillary metastases. Metastases to subpectoral, IMC, supraclavicular, and subclavian lymph nodes could potentially require modification of post-operative radiation therapy fields. (Total 20/38, 52.6%) Conclusions: FDG PET/CT detected positive axillary lymph nodes in 84.2% of breast cancer patients scheduled for neoadjuvant chemotherapy; in 50% of Stage II patients, 96.2% of stage III patients and 100% of Stage IV patients. Extra-axillary metastases were identified in 42.1% of patients, 53.8% of stage III patients and 100 % of stage IV patients. In 52.6 % of patients, non-axillary regional metastases were identified that could potentially change radiation treatment plans. In clinical stage III and limited stage IV disease, FDG/PET CT could contribute to modified radiation treatment planning.

Reply to When randomized trials and observational data disagree: The case of preoperative versus postoperative chemoradiotherapy for esophageal cancer

We thank Palma et al for bringing to our attention the 3arm randomized controlled trial (RCT) from China by Lv et al. We agree with many of the limitations of any Surveillance, Epidemiology, and End Results (SEER) study that they point out. Specifically, confounding because of unmeasured covariates is always a potential source of error in observational studies. However, in our study, we conducted a thorough sensitivity analysis to assess the effects of unmeasured variables, such as clinical tumor staging. A similar sensitivity analysis demonstrated that, even if the preoperative patients were half as likely to have comorbid disease as postoperative patients, our statistically significant results would hold. Palma et al suggest that some of the postoperative patients may have received radiotherapy for palliation of early recurrence after surgery, confounding the results. This is unlikely, because SEER data only capture first course of treatment information within 4 months of the cancer diagnosis, and the likelihood of patients developing recurrence within the first few months after surgery is less than 5% according to recent randomized data. More important, the RCT by Lv et al warrants deeper exploration of the results beyond reading the results and conclusions of the abstract. The lack of difference in outcomes between preoperative and postoperative patients was noted for the entire cohort of patients, which also included patients receiving a “palliative resection or esophageal bypass.” When looking at the overall survival data pertaining only to patients who underwent curative, radical resection (see Lv et al, Fig. 1D), it is clear that there is a trend toward improved overall survival with preoperative treatment. The authors also acknowledge these findings in their discussion section. Therefore, we believe that the data as reported in this RCT, if anything, may lean in favor of preoperative therapy, particularly when considering the lower local recurrence rate with preoperative treatment. Given the limitations of this RCT and our own observational study, we acknowledge that, without a well designed and sufficiently large RCT comparing preoperative versus postoperative treatment, the question of the optimal sequencing of perioperative treatment cannot be definitively answered. We applaud the investigators who are actively studying this topic in the ongoing Quality of Life in Neoadjuvant Versus Adjuvant Therapy of Esophageal Cancer Treatment Trial (QUINTETT) RCT and eagerly await their results.