Effect of Radiation Schedule on Transportation-Related Carbon Emissions: A Case Study in Rectal Cancer.

Purpose: The health care sector is a major contributor of worldwide greenhouse gas (GHG) emissions. Indirect emissions, including those associated with transportation, make up 82% of the US health care sector's environmental footprint. Radiation therapy (RT) treatment regimens present an opportunity for environmental health care-based stewardship owing to the high incidence of cancer diagnosis, significant utilization of RT, and myriad treatment days required for curative regimens. Because the use of short-course RT (SCRT) in the treatment of rectal cancer has demonstrated noninferior clinical outcomes compared with conventional, long-course RT (LCRT), we investigate the environmental and health equity-related outcomes. Methods and Materials: Patients treated with curative, preoperative RT for newly diagnosed rectal cancer at our institution between 2004 and 2022 and living in-state were included. Travel distance was estimated using patients' reported home address. Associated GHG emissions were calculated and reported in carbon dioxide equivalents (CO2e). Results: Of 334 patients included, the total distance traveled for the treatment course was significantly greater in patients treated with LCRT versus SCRT (median, 1417 vs 319 miles; P < .001). Total CO2e emissions for those undergoing LCRT (n = 261) and SCRT (n = 73) were 665.3 kg CO2e and 149.9 kg CO2e, respectively, per treatment course (P < .001), with a net difference of 515.4 kg CO2e. Relatively, this suggests that LCRT is associated with 4.5 times greater GHG emissions from patient transportation. Conclusions: Using treatment of rectal cancer as proof-of-principle, we advocate for the inclusion of environmental considerations in the creation of climate-resilient oncologic RT practices, especially in the context of equivocal clinical outcomes between RT fractionation schedules.

Radiation Therapy for Endometrial Cancer: An American Society for Radiation Oncology Clinical Practice Guideline.

PURPOSE: With the results of several recently published clinical trials, this guideline informs on the use of adjuvant radiation therapy (RT) and systemic therapy in the treatment of endometrial cancer. Updated evidence-based recommendations provide indications for adjuvant RT and the associated techniques, the utilization and sequencing of adjuvant systemic therapies, and the effect of surgical staging techniques and molecular tumor profiling. METHODS: The American Society for Radiation Oncology convened a multidisciplinary task force to address 6 key questions that focused on the adjuvant management of patients with endometrial cancer. The key questions emphasized the (1) indications for adjuvant RT, (2) RT techniques, target volumes, dose fractionation, and treatment planning aims, (3) indications for systemic therapy, (4) sequencing of systemic therapy with RT, (5) effect of lymph node assessment on utilization of adjuvant therapy, and (6) effect of molecular tumor profiling on utilization of adjuvant therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation. RESULTS: The task force recommends RT (either vaginal brachytherapy or external beam RT) be given based on the patient's clinical-pathologic risk factors to reduce risk of vaginal and/or pelvic recurrence. When external beam RT is delivered, intensity modulated RT with daily image guided RT is recommended to reduce acute and late toxicity. Chemotherapy is recommended for patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II with high-risk histologies and those with FIGO stage III to IVA with any histology. When sequencing chemotherapy and RT, there is no prospective data to support an optimal sequence. Sentinel lymph node mapping is recommended over pelvic lymphadenectomy for surgical nodal staging. Data on sentinel lymph node pathologic ultrastaging status supports that patients with isolated tumor cells be treated as node negative and adjuvant therapy based on uterine risk factors and patients with micrometastases be treated as node positive. The available data on molecular characterization of endometrial cancer are compelling and should be increasingly considered when making recommendations for adjuvant therapy. CONCLUSIONS: These recommendations guide evidence-based best clinical practices on the use of adjuvant therapy for endometrial cancer.

Multiblock Discriminant Analysis of Integrative 18F-FDG-PET/CT Radiomics for Predicting Circulating Tumor Cells in Early-Stage Non-small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy.

PURPOSE: The main objective of the present study was to integrate 18F-FDG-PET/CT radiomics with multiblock discriminant analysis for predicting circulating tumor cells (CTCs) in early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic body radiation therapy (SBRT). METHODS: Fifty-six patients with stage I NSCLC treated with SBRT underwent 18F-FDG-PET/CT imaging pre-SBRT and post-SBRT (median, 5 months; range, 3-10 months). CTCs were assessed via a telomerase-based assay before and within 3 months after SBRT and dichotomized at 5 and 1.3 CTCs/mL. Pre-SBRT, post-SBRT, and delta PET/CT radiomics features (n = 1548 × 3/1562 × 3) were extracted from gross tumor volume. Seven feature blocks were constructed including clinical parameters (n = 12). Multiblock data integration was performed using block sparse partial least squares-discriminant analysis (sPLS-DA) referred to as Data Integration Analysis for Biomarker Discovery Using Latent Components (DIABLO) for identifying key signatures by maximizing common information between different feature blocks while discriminating CTC levels. Optimal input blocks were identified using a pairwise combination method. DIABLO performance for predicting pre-SBRT and post-SBRT CTCs was evaluated using combined AUC (area under the curve, averaged across different blocks) analysis with 20 × 5-fold cross-validation (CV) and compared with that of concatenation-based sPLS-DA that consisted of combining all features into 1 block. CV prediction scores between 1 class versus the other were compared using the Wilcoxon rank sum test. RESULTS: For predicting pre-SBRT CTCs, DIABLO achieved the best performance with combined pre-SBRT PET radiomics and clinical feature blocks, showing CV AUC of 0.875 (P = .009). For predicting post-SBRT CTCs, DIABLO achieved the best performance with combined post-SBRT CT and delta CT radiomics feature blocks, showing CV AUCs of 0.883 (P = .001). In contrast, all single-block sPLS-DA models could not attain CV AUCs higher than 0.7. CONCLUSIONS: Multiblock integration with discriminant analysis of 18F-FDG-PET/CT radiomics has the potential for predicting pre-SBRT and post-SBRT CTCs. Radiomics and CTC analysis may complement and together help guide the subsequent management of patients with ES-NSCLC.

Liposomes as Carriers of Membrane-Associated Proteins and Peptides for Mass Spectrometric Analysis.

Membrane proteins are key players of the cell. Their structure and the interactions they form with their lipid environment are required to understand their function. Here we explore liposomes as membrane mimetics for mass spectrometric analysis of peripheral membrane proteins and peptides. Liposomes are advantageous over other membrane mimetics in that they are easy to prepare, can be varied in size and composition, and are suitable for functional assays. We demonstrate that they dissociate into lipid clusters in the gas phase of a mass spectrometer while intact protein and protein-lipid complexes are retained. We exemplify this approach by employing different liposomes including proteoliposomes of two model peptides/proteins differing in size. Our results pave the way for the general application of liposomes for mass spectrometric analysis of membrane-associated proteins.

Universal suicide screening in college primary care.

OBJECTIVE: Implementation of a universal primary care (PC) suicide-screening program in a college student health center to heighten awareness, provide support and enhance education of staff and students served. Program feasibility, data collection, electronic medical record (EMR) adaptations and staff learning outcomes were examined. Participants: 1,607 students with PC visits during Spring 2018 semester. Methods: Annual Suicide Behaviors Questionnaire (SBQ-R), EMR template, safety alert, referral tracking and simulated staff training were employed. Chi-square tests assessed documentation, safety alerts and mental health referral changes. Paired t-tests evaluated staff learning outcomes. Results: 12.8% of students screened positively for suicide risk during implementation. Documentation consistency, EMR safety alert utilization, mental health referrals and subsequent appointments increased significantly. Staff learning outcomes yielded growth in knowledge and comfort with suicide screening and brief intervention. Conclusion: A comprehensive suicide-screening program is feasible for identifying students at-risk and promoting positive clinical changes in college PC practice settings.

Updating Photon-Based Normal Tissue Complication Probability Models for Pneumonitis in Patients With Lung Cancer Treated With Proton Beam Therapy.

PURPOSE: No validated models for predicting the risk of radiation pneumonitis (RP) with proton beam therapy (PBT) currently exist. Our goal was to externally validate and recalibrate multiple established photon-based normal tissue complication probability models for RP in a cohort with locally advanced nonsmall cell lung cancer treated with contemporary doses of chemoradiation using PBT. METHODS AND MATERIALS: The external validation cohort consisted of 99 consecutive patients with locally advanced nonsmall cell lung cancer treated with chemoradiation using PBT. RP was retrospectively scored at 3 and 6 months posttreatment. We evaluated the performance of the photon Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) pneumonitis model, the QUANTEC model adjusted for clinical risk factors, and the newer Netherlands updated QUANTEC model. A closed testing procedure was performed to test the need for model updating, either by recalibration-in-the-large (re-estimation of intercept), recalibration (re-estimation of intercept/slope), or model revision (re-estimation of all coefficients). RESULTS: There were 21 events (21%) of ≥grade 2 RP. The closed testing procedure on the PBT data set did not detect major deviations between the models and the data and recommended adjustment of the intercept only for the photon-based Netherlands updated QUANTEC model (intercept update: -1.2). However, an update of the slope and revision of the model coefficients were not recommended by the closed testing procedure, as the deviations were not significant within the power of the data. CONCLUSIONS: The similarity between the dose-response relationship for PBT and photons for normal tissue complications has been an assumption until now. We demonstrate that the preexisting, widely used photon based models fit our PBT data well with minor modifications. These now-validated and updated normal tissue complication probability models can aid in individualizing selection of the most optimal treatment technique for a particular patient.

Circulating Tumor Cells Are Associated with Recurrent Disease in Patients with Early-Stage Non-Small Cell Lung Cancer Treated with Stereotactic Body Radiotherapy.

PURPOSE: Although stereotactic body radiotherapy (SBRT) is effective in early-stage non-small cell lung cancer (NSCLC), approximately 10%-15% of patients will fail regionally and 20%-25% distantly. We evaluate a novel circulating tumor cell (CTC) assay as a prognostic marker for increased risk of recurrence following SBRT. EXPERIMENTAL DESIGN: Ninety-two subjects (median age, 71 years) with T1a (64%), T1b (23%), or T2a (13%) stage I NSCLC treated with SBRT were prospectively enrolled. CTCs were enumerated by utilizing a GFP-expressing adenoviral probe that detects elevated telomerase activity in cancer cells. Samples were obtained before, during, and serially up to 24 months after treatment. SBRT was delivered to a median dose of 50 Gy (range, 40-60 Gy), mostly commonly in four to five fractions (92%). RESULTS: Thirty-eight of 92 subjects (41%) had a positive CTC test prior to SBRT. A cutoff of ≥5 CTCs/mL before treatment defined favorable (n = 78) and unfavorable (n = 14) prognostic groups. Increased risk of nodal (P = 0.04) and distant (P = 0.03) failure was observed in the unfavorable group. Within 3 months following SBRT, CTCs continued to be detected in 10 of 35 (29%) subjects. Persistent detection of CTCs was associated with increased risk of distant failure (P = 0.04) and trended toward increased regional (P = 0.08) and local failure (P = 0.16). CONCLUSIONS: Higher pretreatment CTCs and persistence of CTCs posttreatment is significantly associated with increased risk of recurrence outside the targeted treatment site. This suggests that CTC analysis may potentially identify patients at higher risk for regional or distant recurrences and who may benefit from either systemic therapy and/or timely locoregional salvage treatment.

Early Detection of Recurrence in Patients With Locally Advanced Non-Small-Cell Lung Cancer via Circulating Tumor Cell Analysis.

BACKGROUND: Assays to identify circulating tumor cells (CTCs) might allow for noninvasive and sequential monitoring of lung cancer. We investigated whether serial CTC analysis could complement conventional imaging for detecting recurrences after treatment in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). PATIENTS AND METHODS: Patients with LA-NSCLC (stage II-III) who definitively received concurrent chemoradiation were prospectively enrolled, with CTCs from peripheral blood samples identified using an adenoviral probe that detects elevated telomerase activity present in nearly all lung cancer cells. A "detectable" CTC level was defined as 1.3 green flourescent protein-positive cells per milliliter of collected blood. Samples were obtained before, during (at weeks 2, 4, and 6), and after treatment (post-radiation therapy [RT]; at months 1, 3, 6, 12, 18, and 24). RESULTS: Forty-eight patients were enrolled. At a median follow-up of 10.9 months, 22 (46%) patients had disease recurrence at a median time of 7.6 months post-RT (range, 1.3-32.0 months). Of the 20 of 22 patients for whom post-RT samples were obtained, 15 (75%) had an increase in CTC counts post-RT. In 10 of these 15 patients, CTCs were undetectable on initial post-RT draw but were then detected again before radiographic detection of recurrence, with a median lead time of 6.2 months and mean lead time of 6.1 months (range, 0.1-12.0 months) between CTC count increase and radiographic evidence of recurrence. One patient with an early recurrence (4.7 months) had persistently elevated detectable CTC levels during and after treatment. CONCLUSION: These results indicate that longitudinal CTC monitoring in patients with LA-NSCLC treated with chemoradiation is feasible, and that detectable CTC levels in many patients meaningfully precede radiologic evidence of disease recurrence.

Mass spectrometry-A versatile tool for characterising the lipid environment of membrane protein assemblies.

Biological membranes are selectively permeable barriers important for cell organization and compartmentalization. Their organisation strongly depends on the lipids that constitute the lipid bilayer as well as the proteins that reside in the membrane. Unravelling the organisation of biological membranes is therefore of great importance to understand cellular function driven by integral and peripheral membrane proteins. Recent developments in mass spectrometry made it a powerful tool contributing to our present-day understanding of membrane composition and organisation. The two main deliverables of mass spectrometry are (i) the identification and quantification of the membrane components, and (ii) the analysis of their structural arrangements. In this review article, we first briefly discuss the aspects of membrane organization that are accessible through mass spectrometry. We then provide detailed insights into the various mass spectrometric strategies which help identifying lipids from membranes or membrane protein assemblies, unravelling the lipid binding modes in membrane proteins and uncovering their structural roles. We further discuss the growing interest in membrane mimetics providing membrane proteins with a native-like lipid environment for structural and functional studies and the possibilities of mass spectrometry to contribute in these experiments.

Five-year Long-term Outcomes of Stereotactic Body Radiation Therapy for Operable Versus Medically Inoperable Stage I Non-small-cell Lung Cancer: Analysis by Operability, Fractionation Regimen, Tumor Size, and Tumor Location.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is standard for medically inoperable stage I non-small-cell lung cancer (NSCLC) and is emerging as a surgical alternative in operable patients. However, limited long-term outcomes data exist, particularly according to operability. We hypothesized long-term local control (LC) and cancer-specific survival (CSS) would not differ by fractionation schedule, tumor size or location, or operability status, but overall survival (OS) would be higher for operable patients. PATIENTS AND METHODS: All consecutive patients with stage I (cT1-2aN0M0) NSCLC treated with SBRT from June 2009 to July 2013 were assessed. Thoracic surgeon evaluation determined operability. Local failure was defined as growth following initial tumor shrinkage or progression on consecutive scans. LC, CSS, and OS were calculated using Cox proportional hazards regression. RESULTS: A total of 186 patients (204 lesions) were analyzed. Most patients were inoperable (82%) with Eastern Cooperative Oncology Group performance status of 1 (59%) or 2 (26%). All lesions received biological effective doses ≥ 100 Gy most commonly (94%) in 3 to 5 fractions. The median follow-up was 4.0 years. LC at 2 and 5 years were 95.6% (95% confidence interval, 92%-99%) and 93.7% (95% confidence interval, 90%-98%), respectively. Compared with operable patients, inoperable patients did not have significant differences in 5-year LC (93.1% vs. 96.7%; P = .49), nodal failure (31.4% vs. 11.0%; P = .12), distant failure (12.2% vs. 10.4%; P = .98), or CSS (80.6% vs. 91.0%; P = .45) but trended towards worse OS (34.2% vs. 45.3%; P = .068). Tumor size, location, and fractionation did not significantly influence outcomes. CONCLUSIONS: SBRT has excellent, durable LC and CSS rates for early-stage NSCLC, although inoperable patients had somewhat lower OS than operable patients, likely owing to greater comorbidities.

Circulating Tumor Cell Assessment in Presumed Early Stage Non-Small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy: A Prospective Pilot Study.

PURPOSE: In patients treated with stereotactic body radiation therapy (SBRT) for presumed early stage non-small cell lung cancer (NSCLC), detection and monitoring of circulating tumor cells (CTCs) may be useful for assessing treatment response safely and noninvasively. No published reports of CTC trends in this patient population exist to date. METHODS AND MATERIALS: Patients with clinically diagnosed stage I NSCLC treated with SBRT were eligible for this institutional review board-approved prospective clinical trial. Peripheral blood samples were assayed for CTCs via a green fluorescent protein-expressing adenoviral probe. CTC positivity was defined as 1.3 green fluorescent protein-positive cells/mL of collected blood. Samples were obtained before (pre-radiation therapy [RT]), during, and after SBRT (post-RT; months 1, 3, 6, 12, 18, and 24). SBRT was delivered in ≤5 fractions (median dose of 50 Gy in 12.5 Gy fractions) to a biological equivalent dose of ≥100 Gy in all cases. RESULTS: Forty-eight consecutive patients (T1a [73%], T1b [21%], and T2a [6%]) were enrolled. Median follow-up was 14.2 months. Twenty patients (42%) had a positive CTC level pre-RT, with a median CTC count of 4.2 CTCs per mL (interquartile range [IQR], 2.2-18.7). Of these 20 patients, 17 had evaluable post-RT CTC evaluations showing reduced CTC counts at 1 month (median, 0.2; IQR, 0.1-0.8) and 3 months (median, 0.6; IQR, 0-1.1). Three of these 17 patients experienced disease progression at a median of 19.9 months; all 3 experienced ≥1 positive post-RT CTC test predating clinical progression by a median of 16 months (range, 2-17 months). In contrast, among patients presenting with CTC-detectable disease and for whom all post-RT CTC tests were negative, none experienced recurrence or progression. CONCLUSIONS: CTC monitoring after SBRT for presumed early stage NSCLC may give lead-time notice of disease recurrence or progression. Conversely, negative CTC counts after treatment may provide reassurance of disease control. CTC analysis is thus potentially useful in enhancing clinical diagnosis and follow-up in this population.

A novel sample preparation strategy for shotgun lipidomics of phospholipids employing multilamellar vesicles.

The identification of lipids in biological samples is gaining importance. The advent of mass spectrometry-based lipidomics accelerated the field allowing nowadays for identification and quantification of complete lipidomes. However, due to solubility difficulties and varying properties of different lipid classes, sample preparation for lipidomics is still an issue. Of the many lipid classes, phospholipids are the major components of biological membranes. In solution, they spontaneously form lipid vesicles of various structures such as liposomes. They are therefore often used as membrane mimics when studying biological membranes and membrane proteins. Here, we present a novel sample preparation strategy for shotgun lipidomics employing liposomes prepared from lipid standards or lipid mixtures allowing the analysis of phospholipids directly from lipid bilayers. We validated our strategy for lipid identification by tandem mass spectrometry in positive or negative ion mode using different phospholipid species from various classes. We further tested our strategy for relative quantification by mixing different ratios of phospholipid species as well as determining the distribution of lipid species in a natural lipid extract. Graphical abstract ᅟ.

The state of survivorship care in radiation oncology: Results from a nationally distributed survey.

BACKGROUND: Survivorship care has become an increasingly critical component of oncologic care as well as a quality practice and reimbursement metric. To the authors' knowledge, the current climate of survivorship medicine in radiation oncology has not been investigated fully. METHODS: An institutional review board-approved, Internet-based survey examining practices and preparedness in survivorship care was distributed to radiation oncology practices participating in the American College of Radiology Radiation Oncology Practice Accreditation program between November 2016 and January 2017. A total of 78 surveys were completed. Among these, 2 were nonphysicians, resulting in 76 evaluable responses. RESULTS: Radiation oncologists (ROs) frequently reported that they are the primary provider in the evaluation of late toxicities and the recurrence of primary cancer. Although approximately 68% of ROs frequently discuss plans for future care with survivors, few provide a written survivorship care plan to their patients (18%) or the patients' primary care providers (24%). Patient prognosis, disease site, and reimbursement factors often influence the provision of survivorship care. Although ROs report that several platforms offer training in survivorship medicine, the quality of these resources is variable and extensive instruction is rare. Fewer than one-half of ROs believe they are expertly trained in survivorship care. CONCLUSIONS: ROs play an active role within the multidisciplinary team in the cancer-related follow-up care of survivors. Investigation of barriers to the provision of survivorship care and optimization of service delivery should be pursued further. The development of high-quality, easily accessible educational programming is needed so that ROs can participate more effectively in the care of cancer survivors. Cancer 2018;124:2653-60. © 2018 American Cancer Society.

Genetic Interactions Between BOB1 and Multiple 26S Proteasome Subunits Suggest a Role for Proteostasis in Regulating Arabidopsis Development.

Protein folding and degradation are both required for protein quality control, an essential cellular activity that underlies normal growth and development. We investigated how BOB1, an Arabidopsis thaliana small heat shock protein, maintains normal plant development. bob1 mutants exhibit organ polarity defects and have expanded domains of KNOX gene expression. Some of these phenotypes are ecotype specific suggesting that other genes function to modify them. Using a genetic approach we identified an interaction between BOB1 and FIL, a gene required for abaxial organ identity. We also performed an EMS enhancer screen using the bob1-3 allele to identify pathways that are sensitized by a loss of BOB1 function. This screen identified genetic, but not physical, interactions between BOB1 and the proteasome subunit RPT2a Two other proteasome subunits, RPN1a and RPN8a, also interact genetically with BOB1 Both BOB1 and the BOB1-interacting proteasome subunits had previously been shown to interact genetically with the transcriptional enhancers AS1 and AS2, genes known to regulate both organ polarity and KNOX gene expression. Our results suggest a model in which BOB1 mediated protein folding and proteasome mediated protein degradation form a functional proteostasis module required for ensuring normal plant development.

Patient-Reported Survivorship Care Practices and Late Effects After Treatment of Hodgkin and Non-Hodgkin Lymphoma.

PURPOSE: Multimodal treatment of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) yields excellent outcomes; however, survivors are at risk of developing myriad late and long-term effects. METHODS: From a convenience sample of 964 survivors of HL (37%) and NHL (63%) using a publicly available Internet-based survivorship care plan (SCP) tool between 2011 and 2016, we examined patient-reported cancer care, toxicities, and survivorship care data. RESULTS: Of all survivors, 67% were female and 84% were white and 88% were free of cancer. Median age of diagnosis was 28 years for survivors of HL and 49 years for NHL. Many survivors reported treatment with chemotherapy (92%), surgery (52%), and/or radiation (41%), with most radiation delivered to chest/mantle fields (81%). Survivors reported a diversity of radiation- and chemotherapy-related sequelae, including thyroid dysfunction, speaking and/or swallowing changes, pulmonary fibrosis/pneumonitis, heart disease, chronic fatigue, neurocognitive decline, neuropathy, sexual changes, and secondary breast cancers. Few reported receipt of previous survivorship information. Most reported management/comanagement by an oncology specialist after active treatment; however, a shift to management by primary care provider alone was observed as a trend over time in follow-up. Sixty-six percent of users who responded to a follow-up survey reported that they intend to share the SCP with their health care team. CONCLUSION: Survivors of lymphoma, many of whom are free of disease, report a substantial burden of late and long-term adverse effects, suboptimal delivery of survivorship information, and transitions of care in follow-up in which fragmented systems and/or poor communication may contribute to unmet survivor needs. Multiple opportunities thus exist for which SCPs may be used to improve awareness regarding survivorship and associated adverse effects in addition to communicating follow-up care plans between survivors and treatment teams.

Outcomes of invasive mediastinal nodal staging versus positron emission tomography staging alone for early-stage non-small cell lung cancer treated with stereotactic body radiation therapy.

BACKGROUND: The benefit of invasive mediastinal nodal staging (IMNS) in addition to positron emission tomography-computed tomography (PET/CT) is undefined for early stage non-small cell lung cancer (NSCLC). This multi-institutional investigation aimed to evaluate outcomes and patterns of failure in patients staged with PET/CT with or without additional IMNS. METHODS: Two academic centers assessed all consecutive patients staged with PET/CT for early-stage, primary lung NSCLC (cT1-2aN0M0) treated with SBRT. Local recurrence-free survival (LRFS), nodal recurrence-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were calculated using Kaplan-Meier methodology. Univariate and multivariate Cox proportional hazards modeling addressed factors associated with outcomes. RESULTS: Overall, 180 patients (199 lesions) were staged with PET/CT alone and 56 patients (58 lesions) underwent additional IMNS. Among patients receiving IMNS, 52 (93%) underwent EBUS and 4 (7%) underwent mediastinoscopy. At a median follow-up of 33.5 months (range, 1.9-80.9 months), there was no significant difference in LRFS (37 vs. 47 months, p=0.309), NRFS (34 vs. 42 months p=0.370), DMFS (36 vs. 47 months, p=0.234) or OS (37 vs. 47 months, p=0.236) between patients undergoing PET/CT-only versus PET/CT+IMNS staging, respectively. Receipt of IMNS did not correlate with any outcome on either univariate or multivariate analysis (p>0.05). Patterns of failure in both groups were similar, including crude isolated nodal failure rates (8% PET/CT-only versus 14% PET+IMNS group, p=0.202). CONCLUSIONS: Patients undergoing IMNS had similar survival and patterns of recurrence as those receiving PET/CT alone. Further study, ideally prospectively, is needed to determine which subgroups might benefit from IMNS.

First Ever Use of Proton Stereotactic Body Radiation Therapy Delivered with Curative Intent to Bilateral Synchronous Primary Renal Cell Carcinomas.

Limited therapeutic options exist for inoperable bilateral kidney tumors. We report the first ever use of proton therapy to treat primary renal cell carcinoma (RCC) and the first report of proton stereotactic body radiation therapy (SBRT) for RCC in an inoperable patient with synchronous RCCs treated with proton SBRT. The patient is a 47-year-old 450-pound female with multiple medical comorbidities, including Stage 3 chronic kidney disease (CKD), who was found to have bilateral renal masses during work-up for cellulitis and sepsis. Following resolution of her sepsis, subsequent cross-sectional imaging demonstrated interval growth of the left renal mass to 4.4 x 4.8 cm and the right renal mass to 2.0 x 2.6 cm. Bilateral biopsies were performed, with pathology revealing Furhman Grade 1-2 clear cell RCC on both sides. A customized SBRT plan delivered a total dose of 3,000 cGy in five fractions to the bilateral kidneys every other day using proton beam therapy. The patient experienced no grade > 1 acute adverse toxicities from proton therapy, and now at one year after treatment, she has had no clinical symptoms of late radiation-induced toxicities. Although a marginal decline in post-treatment glomerular filtration rate (GFR) was observed (baseline 34 mL/min/1.73m2, one-year post-SBRT 29 mL/min/1.73m2), the patient remains asymptomatic and without a requirement for intervention. In presenting a case in which proton SBRT was performed safely and effectively for a medically complex patient with inoperable synchronous bilateral RCC, we suggest that proton therapy is a promising therapeutic approach for even unilateral primary RCC where preservation of renal function is of importance and should be considered for medically inoperable patients. Further experience is needed to determine the optimal dose and fractionation regimen for renal SBRT with proton therapy.

Survivorship after treatment of pancreatic cancer: insights via an Internet-based survivorship care plan tool.

Pancreatic cancer survivors face a unique set of challenges in survivorship, yet structured survivorship care planning is lacking in practice. Survivorship care plans (SCPs) are an essential part of quality cancer care and can facilitate the transition following active treatment; the use of SCPs in pancreatic cancer survivors, however, has not been explored. With a convenience sample of 117 pancreatic cancer survivors and proxies who used an Internet-based SCP tool, we examined treatment details, patient-reported outcomes, and survivorship practices. Thirty-one percent of survivors were 2 years or greater from diagnosis with a median current age of 62 years. Most patients had received multimodality therapy (67%): 68%, 86%, and 43% reported surgical intervention, intravenous chemotherapy, and radiation therapy for their pancreatic cancer, respectively. Survivors commonly reported fatigue, cognitive change, neuropathy, pancreatic insufficiency, and chronic radiation dermatitis related to treatment. Most survivors are managed (47%) or co-managed (35%) by an oncology specialist; however, this percentage decreases over time with consequent increase in management by primary care providers alone. Only 5% had previously been offered an SCP. Of the 24 users who responded to a follow-up satisfaction survey, 83% indicated they would share the SCP with their healthcare team although half of respondents felt it should include more information. In all, our results demonstrate that there is a population of pancreatic cancer survivors who exist and seek survivorship support although structured survivorship care planning is lacking in practice. SCPs have a potentially valuable role for these survivors via communication of treatment-related effects and coordination across multidisciplinary healthcare teams. Further development and evaluation of SCPs is needed for this underserved survivor population.

A prospective study of proton reirradiation for recurrent and secondary soft tissue sarcoma.

BACKGROUND AND PURPOSE: Proton reirradiation for sarcoma has not been previously described. We hypothesized that this strategy would provide favorable toxicity and survival outcomes. MATERIAL AND METHODS: Patients with soft tissue sarcoma in a previously-irradiated field were enrolled on a prospective trial of proton reirradiation. The primary endpoint was provider-reported acute toxicity. Secondary endpoints included late toxicities, local control, and overall survival. RESULTS: 23 patients underwent proton reirradiation. Median time between radiation courses was 40.7months (range 10-272). No grade 4-5 toxicities were observed. One patient (4%) experienced acute grade 3 dysphagia. Common grade 2 acute toxicities were fatigue (26%), anorexia (17%), and urinary incontinence (13%). There were two grade 3 late wound infections (10%) and one grade 3 late wound complication (5%). Grade 2 late complications included lymphedema (10%), fracture (5%), and fibrosis (5%). At a median follow-up of 36months, the 3-year cumulative incidence of local failure was 41% (95% CI [20-63%]). Median overall survival and progression-free survival were 44 and 29months, respectively. In extremity patients, amputation was spared in 7/10 (70%). CONCLUSIONS: Proton reirradiation of recurrent/secondary soft tissue sarcomas is well tolerated. While longer follow-up is needed, early survival outcomes in this high-risk population are encouraging.