Measuring the Integration of Stereotactic Ablative Radiotherapy Plus Surgery for Early-Stage Non-Small Cell Lung Cancer (MISSILE): Long-Term Clinical Outcomes.

INTRODUCTION: For early-stage non-small cell lung cancer (NSCLC), surgery is the preferred approach in operable patients, whereas stereotactic ablative radiotherapy (SABR) is preferred for medically inoperable patients. The combination of neoadjuvant SABR followed by surgery was tested in the MISSILE phase II trial. We report long-term outcomes, beyond 5 years of follow-up. METHODS: Patients diagnosed with T1-2N0M0 NSCLC with good performance status and adequate lung function were enrolled. Patients underwent neoadjuvant SABR followed by lobectomy/wedge resection. Forty enrolled patients received SABR, of which 36 patients proceeded to surgery. RESULTS: The pathologic and major complete response rates were 60% and 63%, respectively. Median follow-up was 6.6 years following surgery. Five-year overall, disease-free and cancer-specific survival were 66.7% (95% CI: 48.8-79.5), 58.3% (95% CI: 40.7-72.4) and 76.4% (95% CI: 58.2-87.4). Five-year local, regional and distant control were 93.5% (95% CI: 76.3-98.4), 80.1% (95% CI: 62.7-90.0) and 82.4% (95% CI: 64.9-91.7). After SABR and surgery, 16.7% (n=6) of patients experienced related grade ≥ 3 adverse events and there were no grade 5 events. CONCLUSION: The combined approach of SABR and surgery was safe and demonstrated reasonable long-term clinical outcomes, but similar to surgery alone.

Loss of MACROD2 drives radioresistance but not cisplatin resistance in HPV-positive head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type worldwide. In recent years, there has been an increase in the rate of HNSCC cases attributed to the infection of the oropharynx by the human papillomavirus (HPV). Given the significant treatment-related toxicities of the current standard of care for HPV-positive HNSCC, there is an urgent need for the development of precision patient stratification and treatment strategies to improve patients' quality of life while maintaining excellent survival rates. We have previously carried out whole genome sequencing of HPV+ HNSCC tumors that failed concurrent cisplatin and radiation treatment and discovered that MACROD2 deletion is enriched among these tumors. In the current study, we sought to investigate the mechanistic role of MACROD2 in HPV+ HNSCC treatment resistance. Our results indicate that MACROD2 depletion in HNSCC cell lines leads to increased cell viability and colony formation capacity. Interestingly, MACROD2 depletion did not alter cisplatin sensitivity but led to an increase in radiation resistance of HPV+ HNSCC cell lines. RNA sequencing and immunofluorescence microscopy demonstrated that MACROD2-depleted HPV+ HNSCC cells displayed elevated levels of hypoxia and an altered DNA damage response. Taken together, this study establishes and characterizes the role of MACROD2 in HPV+ HNSCC radioresistance. Further work is needed to validate MACROD2 as a biomarker of treatment failure and to understand how to overcome the identified molecular mechanisms of resistance.

A randomized phase III trial of stereotactic ablative radiotherapy for patients with up to 10 oligometastases and a synchronous primary tumor (SABR-SYNC): study protocol.

BACKGROUND: Emerging randomized data, mostly from phase II trials, have suggested that patients with oligometastatic cancers may benefit from ablative treatments such as stereotactic ablative radiotherapy (SABR). However, phase III data testing this paradigm are lacking, and many studies have examined SABR in the setting of metachronous oligometastatic disease. The goal of the SABR-SYNC trial is to assess the effect of SABR in patients with oligometastatic cancers and a synchronous primary tumor. METHODS: One hundred and eighty patients will be randomized in a 1:2 ratio between standard of care (SOC) palliative-intent treatments vs. SOC + ablative therapy (SABR preferred) to all sites of known disease. Randomization will be stratified based on histology and number of metastases at enrollment. SABR may be delivered in 1-, 3- and 5-fraction regimens, with recommended doses of 20 Gy, 30 Gy, and 35 Gy, respectively. Non-SABR local modalities (e.g. surgery, thermal ablation, conventional radiation) may be used for treatment of the primary or metastases at the discretion of the treating physicians, if those modalities are clinically preferred. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, time to initiation of next systemic therapy, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor DNA and immunological predictors of outcomes. DISCUSSION: SABR-SYNC will provide phase III data to assess the impact of SABR on overall survival in a population of patients with synchronous oligometastases. The translational component will attempt to identify novel prognostic and predictive biomarkers to aid in clinical decision making. TRIAL REGISTRATION: Clinicaltrials.gov NCT05717166 (registration date: Feb. 8, 2023).

Impact of the COVID-19 Pandemic on Academic Productivity in Oncology: A Journal-, Conference- and Author-Level Analysis.

This study assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on academic productivity in oncology, measured by conference abstracts, journal publications and individual authorship trends, using a reference time frame of 2018 to 2022. To assess overall academic productivity, data was obtained on the number of abstracts and articles submitted and published from a selection of oncology conferences and journals. To assess individual authorship patterns, 200 articles were randomly selected from 2018, and for the first or last authors, publications were tracked over subsequent years. Factors assessed included gender, continent, specialty, MD vs. non-MD and career status (early vs. late). The number of submitted and published conference abstracts trended downward over time between 2018 and 2022 (p=0.11 and p=0.16 respectively). Journal submissions increased to a peak in 2020 and then declined thereafter, but this did not translate into changes in the number of papers published. For the author-level analysis, factors significantly predictive of increasing publication rates in multivariable analysis were late career status (vs. early), clinician status (vs. non-clinician), surgery or public health/epidemiology specialty, and author located in Asia. Further research is needed to help ameliorate the impact of these disparities.

Impact of an Etoposide Chemotherapy Shortage on Patients With Extensive-Stage Small-Cell Lung Cancer: Results of a Natural Experiment.

PURPOSE: A shortage of essential intravenous (IV) etoposide lasted from 2018 until 2020 in Ontario, Canada, allowing for a natural experiment in which external factors (IV etoposide availability) dictated patients' treatment assignment. The purpose of this study was to evaluate the impact of this IV etoposide shortage (IVES) on patient care outcomes. METHODS: Individuals with extensive-stage small-cell lung cancer (ES-SCLC) treated during a pre-IVES (November 2017-October 2018) and IVES (November 2018-October 2019) time intervals were retrospectively reviewed at the Verspeeten Family Cancer Centre. We investigated the association of the shortage on health care utilization and survival using a time-to-event analysis, Cox proportional hazards and logistic regression modeling. RESULTS: A total of 119 patients with ES-SCLC were assessed, 49 in the pre-IVES interval and 70 in the IVES interval. The median age was 68 (IQR, 62-74) years, 48% (n = 57) were male, 33% (n = 39) had CNS metastases, and 69% (n = 82) received first-line systemic therapy. Alternate regimens used for IVES cohort included IV platinum-oral (PO) etoposide, IV platinum-IV irinotecan, and PO etoposide monotherapy. An adjusted multivariable model demonstrated a significant increase in hospitalization (odds ratio, 2.30 [95% CI, 1.01 to 5.24]; P = .047) and shorter progression-free survival (PFS; hazard ratio, 1.79 [95% CI, 1.19 to 2.68]; P = .005) during the IVES. CONCLUSION: This study demonstrated increased hospitalization, and decreased PFS, among patients with ES-SCLC treated with alternate chemotherapy regimens during an IVES. The impact of cancer drug shortages can be harmful, and optimizing a more secure drug supply with mitigation strategies is warranted.

Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Final Results of the ORATOR Randomized Trial.

Radiotherapy (RT) and transoral robotic surgery (TORS) are both curative-intent treatment options for oropharyngeal squamous cell carcinoma (OPSCC). Herein, we report the final outcomes of the ORATOR trial comparing these modalities, 5 years after enrollment completion. We randomly assigned 68 patients with T1-2N0-2 OPSCC to RT (with chemotherapy if node-positive) versus TORS plus neck dissection (± adjuvant RT/chemoradiation). The primary end point was swallowing quality of life (QOL) assessed with the MD Anderson Dysphagia Inventory (MDADI). Secondary end points included overall and progression-free survival (OS, PFS), adverse events (AEs), and other QOL metrics. The primary end point has been previously reported (Nichols 2019). In this report, the median follow-up was 5.1 years (IQR, 5.0-5.3 years). MDADI total scores converged by 5 years and were not significantly different across the follow-up period (P = .11). EORTC QLQ-C30 and H&N35 scores demonstrated differing profiles, including worse dry mouth in the RT arm (P = .032) and worse pain in the TORS arm (P = .002). Grade 2-5 AE rates did not differ between arms (91% [n = 31] v 97% [n = 33] respectively, P = .61), with more neutropenia and hearing loss in the RT arm, and more dysphagia and other pain in the TORS arm based on grades 2-5 (all P < .05). There were no differences in OS or PFS. In conclusion, toxicity and QOL profiles differ in some domains between RT and TORS, but oncologic outcomes were excellent in both arms. Choice of treatment should remain a shared decision between the patient and their providers.

Chemsex Session Typologies and Associated Sociodemographic Factors in Sexual Minority Men: Latent Class Analysis From a Cultural Perspective Using a Cross-Sectional Survey.

Background: Chemsex prevalence is still not well known, and both the lack of homogeneity and cultural component of chemsex practices are usually overlooked. Objective: This study aims to estimate the proportion of sexual minority men (SMM) engaging in chemsex sessions, while understanding the cultural dimension of chemsex, and to analyze distinct session typologies with potential risk differences and the sociodemographic factors associated with engaging in them. Methods: A total of 5711 SMM residing throughout Spain participated in an anonymous web-based survey that assessed chemsex session engagement and characteristics, drug use, and sociodemographic variables. We measured the association of sociodemographic factors with engaging in chemsex sessions by calculating adjusted prevalence ratios, using multivariate Poisson regression analysis. Chemsex typologies were analyzed using latent class analysis, and sociodemographic factors were associated with the different risk classes. Results: Our results determined that 21.1% (1205/5711; 95% CI 20.0%-22.1%) of SMM engaged in chemsex sessions during their lifetime. Participating in sessions was significantly associated with being a migrant, not having a comfortable financial situation, openly living their sexuality, residing in bigger municipalities, older age, using steroids, and living with HIV (adjusted prevalence ratio: range 1.17-2.01; all P values <.05). Three typologies of sessions with different risks were identified with latent class analysis, with 23.2% of SMM engaging in sessions taking part in higher-risk ones, which was associated with younger age, using steroids, living in bigger municipalities, openly living their sexuality, and living with HIV, compared to SMM engaging in lower-risk sessions (odds ratio: range 2.75-4.99). Conclusions: Chemsex is relatively common among SMM in Spain, but it is important to differentiate typologies of sessions with varying risks, and the proportion of SMM engaging in high-risk sessions is low. Chemsex is highly associated with sociodemographic factors. Chemsex should be prioritized in public health programs, which should consider the different forms of sessions with their varying risks and prevalence, while also considering the cultural dimension inherent to chemsex.

Stereotactic Ablative Radiation for Oligoprogressive Cancers: Results of the Randomized Phase 2 STOP Trial.

PURPOSE: This trial examined if patients with ≤5 sites of oligoprogression benefit from the addition of SABR to standard of care (SOC) systemic therapy. METHODS AND MATERIALS: We enrolled patients with 1 to 5 metastases progressing on systemic therapy, and after stratifying by type of systemic therapy (cytotoxic vs noncytotoxic), randomized 1:2 between continued SOC treatment versus SABR to all progressing lesions plus SOC. The trial was initially limited to non-small cell lung cancer but was expanded to include all nonhematologic malignancies to meet accrual goals. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), lesional control, quality of life, adverse events, and duration of systemic therapy postrandomization. RESULTS: Ninety patients with 127 oligoprogressive metastases were enrolled across 8 Canadian institutions, with 59 randomized to SABR and 31 to SOC. The median age was 67 years, and 39 (43%) were women. The most common primary sites were lung (44%), genitourinary (23%), and breast (13%). Protocol adherence in the SOC arm was suboptimal, with 11 patients (35%) either receiving high-dose/ablative therapies (conflicting with trial protocol) or withdrawing from the study. The median follow-up was 31 months. There was no difference in PFS between arms (median PFS 8.4 months in the SABR arm vs 4.3 months in the SOC arm, but curves cross and 2-year PFS was 9% vs 24%, respectively; P = .91). The median OS was 31.2 months versus 27.4 months, respectively (P = .22). Lesional control was superior with SABR (70% vs 38%, respectively; P = .0015). There were 2 (3.4%) grade 3 and no grade 4/5 adverse events attributable to SABR. CONCLUSIONS: SABR was well-tolerated with superior lesional control but did not improve PFS or OS. Accrual to this study was difficult, and the results may have been impacted by an unwillingness to forgo ablative treatments on the SOC arm. (NCT02756793).

Quantum Topological Atomic Properties of 44K molecules.

We present a data set of quantum topological properties of atoms of 44K randomly selected molecules from the GDB-9 data set. These atomic properties were obtained as defined by the quantum theory of atoms in molecules (QTAIM) within an atomic basin, a region of real space bounded by zero-flux surfaces in the electron density gradient vector field. The wave function files were generated through DFT static calculations (B3LYP/6-31G), and the atomic properties were calculated using QTAIM. The calculated atomic properties include the energy of the atomic basin, the electronic population, the magnitude of the total dipole moment, and the magnitude of the total quadrupole moment. The atomic properties allow one to understand the chemical structure, reactivity, and molecular recognition. They can be incorporated into force fields for molecular dynamics or for predicting reactive sites. We believe that this data set could facilitate new studies in chemical informatics, machine learning applied to chemistry, and computational molecular design.

Predicting the 3-Dimensional Dose Distribution of Multilesion Lung Stereotactic Ablative Radiation Therapy With Generative Adversarial Networks.

PURPOSE: Because SABR therapy is being used to treat greater numbers of lung metastases, selecting the optimal dose and fractionation to balance local failure and treatment toxicity becomes increasingly challenging. Multilesion lung SABR therapy plans include spatially diverse lesions with heterogeneous prescriptions and interacting dose distributions. In this study, we developed and evaluated a generative adversarial network (GAN) to provide real-time dosimetry predictions for these complex cases. METHODS AND MATERIALS: A GAN was trained to predict dosimetry on a data set of patients who received SABR therapy for lung lesions at a tertiary center. Model input included the planning computed tomography scan, the organs at risk (OARs) and target structures, and an initial estimate of exponential dose fall-off. Multilesion plans were split 80/20 for training and evaluation. Models were evaluated on voxel-voxel, clinical dose-volume histogram, and conformality metrics. An out-of-sample validation and analysis of model variance were performed. RESULTS: There were 125 multilesion plans from 102 patients with 357 lesions. Patients were treated for 2 to 7 lesions, with 19 unique dose-fractionation schemes over 1 to 3 courses of treatment. The out-of-sample validation set contained an additional 90 plans from 80 patients. The mean absolute difference and gamma pass fraction between the predicted and true dosimetry was <3 Gy and >90% for all OARs. The absolute differences in lung V20 and CV14 were 1.40% ± 0.99% and 75.8 ± 42.0 cc, respectively. The ratios of predicted to true R50%, R100%, and D2cm were 1.00 ± 0.16, 0.96 ± 0.32, and 1.01 ± 0.36, respectively. The out-of-sample validation set maintained mean absolute difference and gamma pass fraction of <3 Gy and >90%, respectively for all OARs. The median standard deviation of variance in V20 and CV14 prediction was 0.49% and 22.2 cc, respectively. CONCLUSIONS: A GAN for predicting the 3-D dosimetry of complex multilesion lung SABR therapy is presented. Rapid dosimetry prediction can be used to assess treatment feasibility and explore dosimetric differences between varying prescriptions.

Stereotactic ablative radiotherapy for oligoprogressive solid tumours: A systematic review and meta-analysis.

INTRODUCTION: The aim of this systematic review and meta-analysis was to review evidence and pool outcomes to assess the effectiveness of stereotactic ablative radiotherapy (SABR) in patients treated for oligoprogressive metastases. METHODS AND MATERIALS: A search was conducted January 2010 to January 2023 in five bibliographic databases for studies of patients with oligoprogressive disease treated with SABR to all lesions. Clinical outcomes included PFS (progression-free survival), OS (overall survival) and CST (change in systemic therapy). Descriptive statistics were used to summarize the data. Binary random effects model was used for pooled analyses. RESULTS: 12,366 titles/abstracts screened, of which 25 met eligibility criteria and were included the review. All studies were published after 2017 with approximately 80% of the publications in 2021 and 2022. The primary tumour was prostate (n=8, 32%), kidney (n=6, 24%), colorectal (n=4, 16%) followed by breast (n=3, 12%), lung (n=2, 8%) and mixed (n=3, 12%). At 1 year, the pooled PFS was 44% (95% confidence interval [CI]: 34-53%, I2=91%); 53% (95% CI: 45-60%, I2=46%) in prostate, 49% (95% CI: 33-65%, I2=88%) in kidney, 62% (95% CI: 11-113%, I2=96%) in lung, 13% (95% CI: 3-24%, I2=39%) in breast and 30% (95% CI: 19-41%, I2=59%) in mixed. DISCUSSION: There has been a surge in publications describing the use of SABR in oligoprogressive tumours. Published studies are mostly retrospective reported in prostate and kidney cancers, with limited evidence in other sites. Universal guidelines are recommended to ensure consistency in reporting and comparability of future studies.

Ablative Radiation Therapy to Restrain Everything Safely Treatable (ARREST): A Phase 1 Study of Stereotactic Ablative Radiation Therapy for Polymetastatic Disease.

PURPOSE: This phase 1 study aimed to assess the safety and feasibility of SABR therapy delivery to all sites of polymetastatic disease (>10 metastases). METHODS AND MATERIALS: A 3 + 3 study design was used with 5 dose levels from 6 Gy (6 Gy × 1) to 30 Gy (6 Gy weekly × 5). Dose-limiting toxicity (DLT) was defined as any grade 4 or 5 toxicity or more than 3 grade 3 toxicities within 6 weeks of treatment. The primary endpoint was the maximal tolerated dose, defined as the dose level where ≥2/6 of patients experienced DLT. Secondary endpoints included quality of life (Functional Assessment of Cancer Therapy - General and European Quality of Life 5 Dimension 5 Level) at 6 weeks posttreatment, progression-free survival, and overall survival. RESULTS: Thirteen patients were accrued: 12 Gy (n = 3), 18 Gy (n = 3), 24 Gy (n = 4), and 30 Gy (n = 3), and 207 lesions were treated. Nine patients (69%) had acute toxicity: grade 1 (n = 6, 46%), grade 2 (n = 2, 15%; n = 1 pneumonitis and n = 1 fatigue), and grade 3 (n = 1, 7.7% neutropenia). There were no grade 4 or 5 toxicities. Mean ± SD quality of life (Functional Assessment of Cancer Therapy - General and European Quality of Life 5 Dimension 5 Level health state) was 80.4 ± 21.9 and 77.4 ± 20.9 at baseline versus 76.4 ± 21.8 and 68.0 ± 24.2 at 6-week follow-up, respectively (p = .009 and p = .055, respectively). With a median follow-up of 8.7 months posttreatment (IQR, 2.4-24 months), 8 of 13 patients had disease progression (62%). The median and 12-month progression-free survival were 3.6 months and 11.3%, respectively. The median and 12-month overall survival were 13.8 months and 62%, respectively. CONCLUSIONS: In this phase 1 trial, SABR therapy for polymetastatic disease was technically feasible with acceptable acute toxicity at dose levels up to 30 Gy (6 Gy weekly × 5). DLT was not observed.

Spin Energy Contributions of the Kinetic Energy Density in the Stabilization of the Metal-Ligand Interactions.

The kinetic energy (KE) density plays an essential role in the stabilization mechanism of covalent, polar covalent, and ionic bondings; however, its role in metal-ligand bindings remains unclear. In a recent work, the energetic contributions of the spin densities α and ß were studied to explain the geometrical characteristics of a series of metal-ligand complexes. Notably, the KE density was found to modulate/stabilize the spin components of the intra-atomic nucleus-electron interactions within the metal in the complex. Here, we investigate the topographic properties of the spin components of the KE density for a family of high-spin hexa-aquo complexes ([M(H2O)6]2+) to shed light on the stabilization of the metal-ligand interaction. We compute the Lagrangian, G(r), and Hamiltonian, K(r), KE densities and analyze the evolution of its spin components in the formation of two metal-ligand coordination complexes. We study Kα/ß(r) along the metal-oxygen (M-O) internuclear axis as a function of the metal. Our results indicate that K(r) is a more distance-sensitive quantity compared to G(r) as it displays topographic features at larger M-O distances. Furthermore, K(r) allows one to identify the predominant interaction mechanism in the complexes.

Clostridium and Cryptosporidium outbreak linked to a splash pad.

BACKGROUND: . Splash pads for recreational purposes are widespread. Using these pads can pose a health risk if they lack installation regulation and water quality supervision. Our aim was to describe a waterborne disease outbreak caused by Clostridium perfringens and Cryptosporidium spp. in a Barcelona district and the measures taken for its control. METHODS: . On August 2018, 71 cases of acute gastroenteritis were detected, affecting people who used a splash pad or were in contact with a user. Microbiological and environmental investigations were carried out. A descriptive analysis of the sample and Poisson regression models adjusted for age and sex were performed, obtaining frequencies, median values, and adjusted prevalence ratios with their 95% confidence intervals. RESULTS: The median age of the cases was 6.7 years, 27 (38%) required medical care, and three (4.2%) were hospitalized. The greater the number of times a person entered the area, the greater the number of symptoms and their severity. Nineteen (76%) of the 25 stool samples collected from cases showed the presence of one or both pathogens. Environmental investigations showed deficiencies in the facilities and identified the presence of both species in the splash pad. Health education and hygiene measures were carried out, and 14 days after the closure of the facilities, no more cases related to the pad were recorded. CONCLUSIONS: . Specific regulations are needed on the use of splash pads for recreational purposes. Until these regulations are in place, these types of facility should comply with the regulations that apply to swimming pools and spas, including those related to the design of the tanks, water recirculation systems, and adequate disinfection systems.

Evaluation of chest CT-scans following lung stereotactic ablative radiotherapy: Challenges and new insights.

Stereotactic ablative radiotherapy (SABR) is increasingly used for the treatment of early-stage non-small cell lung cancer (ES-NSCLC) and for pulmonary metastases. In patients with ES-NSCLC, SABR is highly successful with reported 5-year local control rates of approximately 90%. However, the assessment of local control following lung SABR can be challenging as radiological changes arising from radiation-induced lung injury (RILI) can be observed in up to 90% of patients. These so-called 'benign' radiological changes evolve with time and are often asymptomatic. Several radiological and metabolic features have been explored to help distinguish RILI from local recurrences (LR). These include the Response Evaluation Criteria for Solid Tumors (RECIST), high-risk features (HRF's) and maximum standardized uptake value (SUVmax) on FDG-PET-CT. However, use of some of these approaches have poor predictive values and low specificity for recurrence. A proposed new workflow for the evaluation of post-lung SABR radiological changes will be reviewed which uses the presence of so-called 'actionable radiological features' to trigger changes to imaging schedules and identifies the need for a multidisciplinary board review. Furthermore, this critical review of post-lung SABR imaging will highlight current challenges, new insights, and unknowns in this field.

Optimal management of radiation pneumonitis: Findings of an international Delphi consensus study.

PURPOSE: Radiation pneumonitis (RP) is a dose-limiting toxicity for patients undergoing radiotherapy (RT) for lung cancer, however, the optimal practice for diagnosis, management, and follow-up for RP remains unclear. We thus sought to establish expert consensus recommendations through a Delphi Consensus study. METHODS: In Round 1, open questions were distributed to 31 expert clinicians treating thoracic malignancies. In Round 2, participants rated agreement/disagreement with statements derived from Round 1 answers using a 5-point Likert scale. Consensus was defined as ≥ 75 % agreement. Statements that did not achieve consensus were modified and re-tested in Round 3. RESULTS: Response rate was 74 % in Round 1 (n = 23/31; 17 oncologists, 6 pulmonologists); 82 % in Round 2 (n = 19/23; 15 oncologists, 4 pulmonologists); and 100 % in Round 3 (n = 19/19). Thirty-nine of 65 Round 2 statements achieved consensus; a further 10 of 26 statements achieved consensus in Round 3. In Round 2, there was agreement that risk stratification/mitigation includes patient factors; optimal treatment planning; the basis for diagnosis of RP; and that oncologists and pulmonologists should be involved in treatment. For uncomplicated radiation pneumonitis, an equivalent to 60 mg oral prednisone per day, with consideration of gastroprotection, is a typical initial regimen. However, in this study, no consensus was achieved for dosing recommendation. Initial steroid dose should be administered for a duration of 2 weeks, followed by a gradual, weekly taper (equivalent to 10 mg prednisone decrease per week). For severe pneumonitis, IV methylprednisolone is recommended for 3 days prior to initiating oral corticosteroids. Final consensus statements included that the treatment of RP should be multidisciplinary, the uncertainty of whether pneumonitis is drug versus radiation-induced, and the importance risk stratification, especially in the scenario of interstitial lung disease. CONCLUSIONS: This Delphi study achieved consensus recommendations and provides practical guidance on diagnosis and management of RP.

Delphi consensus on stereotactic ablative radiotherapy for oligometastatic and oligoprogressive renal cell carcinoma-a European Society for Radiotherapy and Oncology study endorsed by the European Association of Urology.

The purpose of this European Society for Radiotherapy and Oncology (ESTRO) project, endorsed by the European Association of Urology, is to explore expert opinion on the management of patients with oligometastatic and oligoprogressive renal cell carcinoma by means of stereotactic ablative radiotherapy (SABR) on extracranial metastases, with the aim of developing consensus recommendations for patient selection, treatment doses, and concurrent systemic therapy. A questionnaire on SABR in oligometastatic renal cell carcinoma was prepared by a core group and reviewed by a panel of ten prominent experts in the field. The Delphi consensus methodology was applied, sending three rounds of questionnaires to clinicians identified as key opinion leaders in the field. At the end of the third round, participants were able to find consensus on eight of the 37 questions. Specifically, panellists agreed to apply no restrictions regarding age (25 [100%) of 25) and primary renal cell carcinoma histology (23 [92%] of 25) for SABR candidates, on the upper threshold of three lesions to offer ablative treatment in patients with oligoprogression, and on the concomitant administration of immune checkpoint inhibitor. SABR was indicated as the treatment modality of choice for renal cell carcinoma bone oligometatasis (20 [80%] of 25) and for adrenal oligometastases 22 (88%). No consensus or major agreement was reached regarding the appropriate schedule, but the majority of the poll (54%-58%) retained the every-other-day schedule as the optimal choice for all the investigated sites. The current ESTRO Delphi consensus might provide useful direction for the application of SABR in oligometastatic renal cell carcinoma and highlight the key areas of ongoing debate, perhaps directing future research efforts to close knowledge gaps.

Outcomes for potentially Resectable patients undergoing primary chemoradiation treatment for T1-T2 HPV Negative oropharyngeal squamous cell carcinoma.

BACKGROUND: Transoral surgical resectability (TOS) is a prognostic factor for patients with HPV+ T1-2 oropharyngeal squamous cell carcinoma (OPSCC) disease undergoing radiotherapy (RT), but it is unclear whether this holds for HPV-negative (HPV-) patients. We aimed to compare outcomes of potential TOS-candidates vs. non-TOS candidates, among patients who underwent RT/CRT for early T-stage HPV- OPSCC. METHODS: For patients treated with RT/CRT for early T-stage HPV-negative OPSCC between 2014 and 2021, pretreatment imaging was reviewed by four head-and-neck surgeons, masked to clinical outcomes, to assess primary-site suitability for TOS. Extracapsular extension (ECE) was assessed by a head-and-neck neuroradiologist. We compared outcomes based on surgical resectability relating to: (1) the primary site tumor alone, and (2) the primary site plus the absence/presence of ECE (overall assessment). Kaplan-Meier curves for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were compared using the log-rank test. RESULTS: Seventy patients were included in the analysis. The primary site was TOS-favorable in 46/70 (66%). Based on the overall assessment, 41/70 (58.6%) were TOS-favorable. The 3-year OS, DSS and PFS for primary site TOS-favorable versus unfavorable were OS: 76.9% versus 37.4%; DSS: 78.1% versus 46.2%, PFS: 69.9% versus 41.3%, (log-rank test = 0.01, 0.03, 0.04; respectively). Additionally, patients with an overall assessment of TOS favorability demonstrated better survival outcomes compared with TOS-unfavorable patients (OS: 77.3% vs. 46.2%; DSS: 78.2% vs. 56.5%, PFS: 72.3% vs. 42.1%, log-rank test = 0.01, 0.04, 0.01; respectively). CONCLUSION: Patients with TOS-favorable HPV-negative early T-stage OPSCC have superior survival outcomes than TOS-unfavorable patients.

Sarcopenia as a Predictor of Feeding Tube Placement in Individuals with Oropharyngeal Cancer.

Purpose: In oropharyngeal squamous cell carcinoma (OPSCC), systemic loss of skeletal muscle mass (SMM), or sarcopenia, is a strong prognostic predictor of survival outcomes. However, the relationship between sarcopenia and nutrition-related outcomes is not well understood. This investigation evaluated the prognostic significance of sarcopenia for feeding tube (FT) placement in a cohort of OPSCC patients. Methods and Materials: A retrospective cohort study was conducted with data collected from 194 OPSCC patients treated with definitive radiation therapy (RT) or chemoradiation therapy (CRT). Sarcopenia was assessed from computed tomography imaging at the level of the third cervical (C3) and fourth thoracic (T4) vertebrae. The prognostic nature of pretreatment sarcopenia and its relationship with FT placement was explored using logistic regression. Results: The median age of patients included was 61.0 years, and the majority were male (83%). In this patient cohort, 87.6% underwent concurrent CRT, and 30.9% received a FT over the course of treatment. Sarcopenia was identified at baseline in 72.7% of patients based on C3 SMM measurements and in 41.7% based on measures at the level of T4. Based on measures at both C3 and T4, those with sarcopenia were significantly more likely to receive a FT and had significantly worse freedom from FT placement compared with patients without sarcopenia. Sarcopenia assessed at T4 was a significant predictor of FT placement. Conclusions: SMM measured at T4 may represent a novel and practical biomarker for sarcopenia detection that is associated with the need for FT placement. These findings suggest that the detection of baseline sarcopenia could guide decision-making related to the need for nutritional support in OPSCC patients undergoing RT/CRT.

Diagnostic CT-Enabled Planning (DART): Results of a Randomized Trial in Palliative Radiation Therapy.

PURPOSE: Using diagnostic computed tomography (dCT) scans instead of CT simulation (CTsim) scans can increase departmental efficiency and reduce patient burden. The goal of the DART trial was to assess the efficacy and acceptability of dCT-based planning workflows with a focus on patient experiences, plan deliverability and adequacy of target coverage, and workflows. METHODS AND MATERIALS: Patients undergoing same-day CTsim and treatment for palliative radiation therapy to thoracic, abdominopelvic, or proximal limb targets with a recent dCT (within 28 days) in a reproducible position were eligible. After stratifying by target type (bone or soft tissue vs. visceral), participants were randomized (1:2 ratio) between CTsim-based (CTsim arm) vs. dCT-based planning (dCT arm). The primary endpoint was time in center (TIC), defined as total time spent in the cancer center on first day of treatment, from first radiation department appointment to first fraction completion. Secondary endpoints included plan deliverability, adequacy of target coverage, and stakeholder acceptability. RESULTS: Thirty-three patients (42 treatment sites) were enrolled between June 2022 and April 2023. The median age was 72 (interquartile range [IQR]: 67-78), 73% were male, and the most common primary cancers were lung (33%), prostate (24%), and breast (12%). The most common dose and fractionations were 8 Gy in 1 and 20 Gy in 5 fractions (50% and 43% of plans, respectively). TIC was 4.7 ± 1.1 hours (mean ± SD) in the CTsim arm vs. 0.41 ± 0.14 hours in the dCT arm (P < .001). All dCT plans were deliverable. All plans in both arms were rated as "acceptable" (80% CTsim; 81% dCT) or "acceptable with minor deviation" (20% CTsim; 19% dCT). Patient perception of acceptability was similar in both arms with the exception of time burden, which was rated as "acceptable" by 50% in the CTsim arm vs. 90% in the dCT arm (P = .025). CONCLUSION: dCT-based radiation planning substantially reduced TIC without detriment in plan deliverability or quality and had a tangible impact on patient experience with reduced patient-reported time burden.