A Case Report of Bilateral Adrenal Gland Stereotactic Body Radiotherapy to Manage Hypercortisolemia in a Patient With Ectopic Adrenocorticotropic Hormone (ACTH) Production From a Metastatic Pancreatic Neuroendocrine Tumor.

A 63-year-old woman presented with hypokalemia, hypertension, weight gain, limb edema, and tremors. She was diagnosed with Cushing syndrome, with a 24-hour urine cortisol level of 41,013 nmol/day. Investigations revealed a grade 2 pancreatic neuroendocrine tumor with extensive hepatic metastases. Owing to excessive adrenocorticotropic hormone production from her disease, her hypercortisolemia and Cushing symptoms worsened despite ketoconazole, somatostatin analogs, and right liver lobe chemoembolization. Stereotactic body radiotherapy (SBRT) at a dose of 39 Gy in three fractions was administered to her bilateral adrenal glands in the hope of reducing her cortisol levels and improving her symptoms. Her 24-hour urine cortisol levels decreased following SBRT, but not rapidly enough; her clinical condition continued to deteriorate, and she died 21 days after treatment. SBRT was not effective as an urgent intervention in this setting; a greater latency to realize a response is likely necessary.

External Beam Radiation Therapy for Palliation of Symptomatic Bone Metastases: An ASTRO Clinical Practice Guideline.

PURPOSE: This guideline provides evidence-based recommendations for palliative external beam radiation therapy (RT) in symptomatic bone metastases. METHODS: The ASTRO convened a task force to address 5 key questions regarding palliative RT in symptomatic bone metastases. Based on a systematic review by the Agency for Health Research and Quality, recommendations using predefined consensus-building methodology were established; evidence quality and recommendation strength were also assessed. RESULTS: For palliative RT for symptomatic bone metastases, RT is recommended for managing pain from bone metastases and spine metastases with or without spinal cord or cauda equina compression. Regarding other modalities with RT, for patients with spine metastases causing spinal cord or cauda equina compression, surgery and postoperative RT are conditionally recommended over RT alone. Furthermore, dexamethasone is recommended for spine metastases with spinal cord or cauda equina compression. Patients with nonspine bone metastases requiring surgery are recommended postoperative RT. Symptomatic bone metastases treated with conventional RT are recommended 800 cGy in 1 fraction (800 cGy/1 fx), 2000 cGy/5 fx, 2400 cGy/6 fx, or 3000 cGy/10 fx. Spinal cord or cauda equina compression in patients who are ineligible for surgery and receiving conventional RT are recommended 800 cGy/1 fx, 1600 cGy/2 fx, 2000 cGy/5 fx, or 3000 cGy/10 fx. Symptomatic bone metastases in selected patients with good performance status without surgery or neurologic symptoms/signs are conditionally recommended stereotactic body RT over conventional palliative RT. Spine bone metastases reirradiated with conventional RT are recommended 800 cGy/1 fx, 2000 cGy/5 fx, 2400 cGy/6 fx, or 2000 cGy/8 fx; nonspine bone metastases reirradiated with conventional RT are recommended 800 cGy/1 fx, 2000 cGy/5 fx, or 2400 cGy/6 fx. Determination of an optimal RT approach/regimen requires whole person assessment, including prognosis, previous RT dose if applicable, risks to normal tissues, quality of life, cost implications, and patient goals and values. Relatedly, for patient-centered optimization of treatment-related toxicities and quality of life, shared decision making is recommended. CONCLUSIONS: Based on published data, the ASTRO task force's recommendations inform best clinical practices on palliative RT for symptomatic bone metastases.

A Systematic Review of Prognostic Factors in Patients with Cancer Receiving Palliative Radiotherapy: Evidence-Based Recommendations.

(1) Background: Prognostication in patients with cancer receiving palliative radiotherapy remains a challenge. To improve the process, we aim to identify prognostic factors in this population from the literature and offer evidence-based recommendations on prognostication in patients undergoing palliative radiotherapy for non-curable or advanced cancers. (2) Methods: A systematic review was performed on the medical literature from 2005 to 2023 to extract papers on the prognosis of palliative radiotherapy patients with advanced cancer. The initial selection was performed by at least two authors to determine study relevance to the target area. Studies were then classified based on type and evidence quality to determine final recommendations. (3) Results: The literature search returned 57 papers to be evaluated. Clinical and biological prognostic factors were identified from these papers to improve clinical decision making or construct prognostic models. Twenty prognostic models were identified for clinical use. There is moderate evidence supporting (i) evidence-based factors (patient, clinical, disease, and lab) in guiding decision making around palliative radiation; (ii) that certain biological factors are of importance; (iii) prognostication models in patients with advanced cancer; and that (iv) SBRT or re-irradiation use can be guided by predictions of survival by prognostic scores or clinicians. Patients with more favorable prognoses are generally better suited to SBRT or re-irradiation, and the use of prognostic models can aid in this decision making. (4) Conclusions: This evaluation has identified several factors or tools to aid in prognosis and clinical decision making. Future studies should aim to further validate these tools and factors in a clinical setting, including the leveraging of electronic medical records for data availability. To increase our understanding of how causal factors interact with palliative radiotherapy, future studies should also examine and include prediction of response to radiation as an outcome.

A 15-Year Single-Institution Retrospective Study of Primary Pancreatic Cancer Treated with Non-Ablative Palliative Radiotherapy.

We studied the use of palliative radiotherapy (RT) among patients with primary, non-curable, locally advanced pancreatic cancer. In this subset of patients, with very poor survival, various palliative RT dose fractionation schemes are used; but, in the absence of a guideline, practice patterns vary, and dose choice is mainly based on the physician's intuition. We divided the patients into three groups, according to the dose fractionation schedules received: low (A), intermediate (B), and high (C) dose groups, to study the potential differences in outcome between the different dose prescriptions. Cohort: n = 184. Median age: 69 years. Male: n = 105 (57%), female: n = 79 (43%). Stage IV: n = 117 (64%). T4: n = 127 (69%). Tumor location: head: n = 109 (59%), body: n = 37 (20%), tail: n = 25 (14%), neck: n = 11 (6%), and uncinate: n = 2 (1%). Prior systemic therapy: n = 66 (36%). Most common dose fractionations received: 20 Gy in five fractions n = 67 (36%), 30 Gy in 10 fractions n = 49 (27%), and 8 Gy in one fraction n = 23 (13%). Group A: n = 33 (18%), median overall survival (OS) 19 days (95% CI 4-33). Group B: n = 84 (46%), median OS 52 days (95% CI 43-60). Group C: n = 67 (36%), median OS 126 days (95% CI 77-174). Median days to in-field progression: Group A 59 days (range 7-109), Group B 96 days (range 19-173), and Group C 97 days (range 13-475). To our knowledge, this is the largest reported retrospective cohort of patients receiving non-ablative palliative RT to treat their primary pancreatic tumors. Most patients had metastatic disease, T4 tumors of the pancreatic head and had not received prior systemic therapy. A significant survival benefit was seen favoring the high dose/longer RT fractionation group, presumably due to appropriate patient selection rather than an RT effect. Despite the relatively short median overall survival, one fifth of the patients were found to experience an in-field progression following RT.

Radiotherapy for Metastatic Epidural Spinal Cord Compression with Increased Doses: Final Results of the RAMSES-01 Trial.

Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 × 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 × 2.633 Gy (41.6 Gy10) or 18 × 2.333 Gy (43.2 Gy10) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score-adjusted Cox regression) to a historical control group (n = 266) receiving 10 × 3.0 Gy (32.5 Gy10). In the phase 2 cohort, 50 (of 62 planned) patients were evaluated for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (p = 0.039) and a trend for improved motor function (p = 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 × 2.633 Gy or 18 × 2.333 Gy was well tolerated and appeared superior to 10 × 3.0 Gy.

Emergent radiotherapy for pelvic malignancies: a narrative review.

BACKGROUND AND OBJECTIVE: Patients with primary genitourinary (GU), gynecologic (GYN) and gastrointestinal (GI) cancers can develop life-threatening or critical function-threatening symptoms that necessitate emergent intervention with palliative radiotherapy (RT). Unfortunately, research describing the use of RT in this critical setting is lacking. We aimed to review literature describing emergent palliative RT for primary pelvic malignancies and provide a narrative synthesis of relevant studies. METHODS: A medical librarian searched Ovid MEDLINE, Embase Classic, and Embase databases for relevant English language references from 1946-2022. No restrictions were placed on study type, publication type or date. References for GU, GYN and GI cancers were grouped and synthesized separately. KEY CONTENT AND FINDINGS: The treatment of bleeding from primary pelvic tumors was the only indication for emergent RT identified, however, no references reported dedicated cohorts of patients treated for bleeding in the emergent setting. Most references were retrospective single institution studies describing various dose fractionation schemes for non-emergent palliative RT. Outcome measures and response assessment times varied. The latency to hemostasis after RT commencement was not well described; most studies reported outcomes captured weeks or months following treatment. In general, high rates of hemostasis for GU, GYN and GI tumors have been reported following RT schedules ranging from a single fraction to many weeks of fractionated treatments. Bleeding seems to respond more favorably than other symptoms including pain and obstruction. CONCLUSIONS: Managing bleeding was the only indication for emergent RT identified in our search. Scant data exist that describe the latency to a hemostatic response following RT. This is an important knowledge gap in the literature given how commonly patients are affected by this complication of primary pelvic malignancies.

2023 Updated MASCC/ESMO Consensus Recommendations: prevention of radiotherapy- and chemoradiotherapy-induced nausea and vomiting.

PURPOSE: Radiotherapy and chemoradiotherapy-induced nausea and vomiting (RINV and C-RINV) are common and distressing, and there is a need for guidance for clinicians to provide up to date optimal antiemetic prophylaxis and treatment. Through a comprehensive review of the literature concerning RINV and C-RINV, this manuscript aims to update the evidence for antiemetic prophylaxis and rescue therapy and provide a new edition of recommendations for the MASCC/ESMO antiemetic guidelines for RINV and C-RINV. METHODS: A systematic review of the literature including data published from May 1, 2015, to January 31, 2023, was performed. All authors assessed the literature. RESULTS: The searches yielded 343 references; 37 met criteria for full article review, and 20 were ultimately retained. Only one randomized study in chemoradiation had the impact to provide new recommendations for the antiemetic guideline. Based on expert consensus, it was decided to change the recommendation for the "low emetic risk" category from "prophylaxis or rescue" to "rescue" only, while the drugs of choice remain unchanged. CONCLUSION: As for the previous guideline, the serotonin receptor antagonists are still the cornerstone in antiemetic prophylaxis of nausea and vomiting induced by high and moderate emetic risk radiotherapy. The guideline update provides new recommendation for the management of C-RINV for radiotherapy and concomitant weekly cisplatin. To avoid overtreatment, antiemetic prophylaxis is no longer recommended for the "low emetic risk" category.

A Case Report of an Isolated Cardiac Metastasis in a Patient with Esophageal Carcinoma.

A 76-year-old Caucasian male presented with syncope, intermittent melena, anemia, and unexplained weight loss. Esophagogastroduodenoscopy revealed a friable non-obstructing esophageal tumor that appeared thickened on computed tomography (CT). Biopsies confirmed a poorly differentiated carcinoma. Fluorine-18 fluorodeoxyglucose positron emission tomography/CT (F-18 FDG PET/CT) showed intense FDG avidity with a maximum standardized uptake value (SUVmax) of 23. Although CT did not identify any lymphadenopathy or distant metastases, a mildly enhancing lobulated circumscribed mass with no internal calcification was incidentally identified in the left atrium. Cardiac magnetic resonance imaging (MRI) favored myxoma over thrombus given the signal characteristics and mild enhancement; however, F-18 FDG PET/CT showed an SUVmax of 18, more consistent with a metastasis. The cardiac mass was resected and shown to be a metastatic focus of poorly differentiated carcinoma, histologically identical to the esophageal mass. He received a single 8 Gray (Gy) fraction of urgent hemostatic radiotherapy for his primary tumor followed by palliative chemotherapy with cisplatin, capecitabine, and pembrolizumab. He was readmitted for transfusion due to recurrent bleeding from his primary tumor and given a second urgent hemostatic fraction of 8 Gy for stabilization. Systemic therapy was eventually discontinued due to declining performance status. He received consolidative palliative radiotherapy (20Gy in five fractions) but continued to deteriorate over the next three months and died in hospice, ten months from the time of his initial presentation.

Ablative vs. Non-Ablative Radiotherapy in Palliating Locally Advanced Pancreatic Cancer: A Single Institution Experience and a Systematic Review of the Literature.

We studied the dose-local control (LC) relationship in ablative vs. non-ablative radiotherapy in a non-radical treatment setting of "locally advanced pancreatic cancer (LAPC)" by comparing our patients (n = 89) treated with SBRT on the CyberKnife unit vs. conventional radiation between January 2005 and January 2021, and by reviewing the literature. A systematic search was performed leveraging Medline for references on SBRT use in pancreatic cancer without date terms or language restrictions. A total of 3702 references were identified and the search was then repeated in Embase and the Cochrane database. Ultimately, 12 studies were eligible for inclusion, which either compared SBRT to conventional radiation, or SBRT use in dose escalation for primary LAPC in a non-neoadjuvant setting. Our cohort's median overall survival was 152 days (CI 95%, 118-185); including 371 days (CI 95%, 230-511) vs. 126 days (CI 95%, 90-161) favoring SBRT, p = 0.004. The median time to local progression was 170 days (48-923) for SBRT vs. 107 days (27-489) for the non-ablative group. In our SBRT patients, no local progressions were seen with BED10 > 60 Gy. Even when palliating LAPC, SBRT should be considered as an alternative to conventional radiation, especially in patients with a low disease burden. BED10 ≥ 60-70 Gy offers better local control without increasing toxicity rates. Less local progression may provide a better quality of life to those patients who already have a short life expectancy.

Equity in adjuvant radiotherapy utilization in locally advanced head and neck cancer: A SEER-data based study.

BACKGROUND: Not all patients with locally advanced head and neck cancer (HNC) who are eligible for adjuvant radiotherapy (RT) following upfront surgery appear to receive it. METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Selected patients from 2009 to 2018 had locally advanced HNC, underwent upfront surgery, and were eligible for adjuvant RT. Multivariable logistic regression and chi-squared test were used to analyze available patient and tumor characteristics. RESULTS: Of 12 549 patients, 84.5% underwent adjuvant RT, 15.5% did not. Characteristics associated with lowest adjuvant RT utilization included cancers of the larynx (p < 0.0001) and gingivae (p < 0.0001), age 80 and above (p < 0.0001), unpartnered status (p < 0.0001), and residence within a nonmetropolitan area (p < 0.0024). CONCLUSIONS: Tumor subsite, age, partnered status, and rural/urban residence correlate with omission of adjuvant RT in locally advanced HNC.

A shift from simple to sophisticated: using intensity-modulated radiation therapy in conventional nonstereotactic palliative radiotherapy.

PURPOSE OF REVIEW: The authors aimed to highlight trends in, and evidence underlying the use of highly conformal radiotherapy (RT) techniques in conventional nonstereotactic palliative RT. The authors reviewed palliative-intent and curative-intent studies relevant to the use of intensity-modulated radiation therapy (IMRT) for the delivery of nonstereotactic conventional regimens to the brain, head and neck, thorax, abdomen and pelvis, and bone metastases. RECENT FINDINGS: The use of IMRT has become standard with certain indications for brain metastases such as hippocampus-avoiding/limiting whole brain RT. IMRT in the treatment of bone metastases is increasing at many institutions despite limited data comparing its effectiveness with that of fluoroscopy-based and three-dimensional conformal radiation therapy techniques. There is scant data describing the use of IMRT for palliation in other extracranial anatomic sites; guidance for its use in these settings must be gleaned almost exclusively from curative-intent randomized trials, consensus recommendations and contouring atlases. SUMMARY: Consistent with historical technology shifts in RT practice, the uptake of highly conformal techniques such as IMRT for conventional palliative RT will likely outpace rigorous evaluations of their advantages and disadvantages relative to simpler techniques. Opportunities exist in virtually all anatomic sites for observational and randomized studies to evaluate the clinical impacts of these modern techniques in the palliative setting.

International Validation of the EORTC QLQ-ANL27, a Field Study to Test the Anal Cancer-Specific Health-Related Quality-of-Life Questionnaire.

PURPOSE: The European Organisation for Research and Treatment of Cancer (EORTC) health-related quality of life questionnaire for anal cancer (QLQ-ANL27) supplements the EORTC cancer generic measure (QLQ-C30) to measure concerns specific to people with anal cancer treated with chemoradiotherapy. This study tested the psychometric properties and acceptability of the QLQ-ANL27. METHODS AND MATERIALS: People with anal cancer were recruited from 15 countries to complete the QLQ-C30 and QLQ-ANL27 and provide feedback on the QLQ-ANL27. Item responses, scale structure (multitrait scaling, factor analysis), reliability (internal consistency and reproducibility) and sensitivity (known group comparisons and responsiveness to change) of the QLQ-ANL27 were evaluated. RESULTS: Data from 382 people were included in the analyses. The EORTC QLQ-ANL27 was acceptable, comprehensive, and easy to complete, taking an average 8 minutes to complete. Psychometric analyses supported the EORTC QLQ-ANL27 items and reliability (Cronbach's α ranging from 0.71-0.93 and test-retest coefficients above 0.7) and validity of the scales (particularly nonstoma bowel symptoms and pain/discomfort). Most scales distinguished people according to treatment phase and performance status. Bowel (nonstoma), pain/discomfort, and vaginal symptoms were sensitive to deteriorations over time. The stoma-related scales remained untested because of low numbers of people with a stoma. Revisions to the scoring and question ordering of the sexual items were proposed. CONCLUSIONS: The QLQ-ANL27 has good psychometric properties and is available in 16 languages for people treated with chemoradiotherapy for anal cancer. It is used in clinical trials and has a potential role in clinical practice.

A dose perturbation tool for robotic radiosurgery: Experimental validation and application to liver lesions.

BACKGROUND: An analytical tool is empirically validated and used to assess the delivered dose to liver lesions accounting for different types of errors in robotic radiosurgery treatment. MATERIAL AND METHODS: A tool is proposed to estimate the target doses taking into account the translation, rotation, and deformation of a target. Translational errors are modeled as a spatial convolution of the planned dose with a probability distribution function derived from treatment data. Rotations are modeled by rotating the target volume about the imaging isocenter. Target deformation is simulated as an isotropic target expansion or contraction based on changes in inter-fiducial spacing. The estimated dose is validated using radiochromic film measurements in nine experimental conditions, including in-phase and out-of-phase internal-and-external breathing motion patterns, with and without uncorrectable rotations, and for homogenous and heterogeneous phantoms. The measured dose is compared to the perturbed and planned doses using gamma analyses. This proposed tool is applied to assess the dose coverage for liver treatments using D99/Rx where D99 and Rx are the minimum target and prescription doses, respectively. These metrics are used to evaluate plan robustness to different magnitudes of rotational errors. Case studies are presented to illustrate how to improve plan robustness against delivery errors. RESULTS: In the experimental validations, measured dose agrees with the estimated dose at the 2%/2 mm level. When accounting for translational and rotational tracking residual errors using this tool, approximately one-fifth of targets are considered underdosed (D99/Rx < 1.0). If target expansion or contraction is modeled, approximately one-third of targets are underdosed. The dose coverage can be improved if treatments are planned following proposed guidelines. CONCLUSION: The dose perturbation model can be used to assess dose delivery accuracy and investigate plan robustness to different types of errors.

Systematic review of brachytherapy for symptom palliation.

PURPOSE: Brachytherapy is most often applied in the curative or salvage setting, but many forms of brachytherapy can be helpful for symptom palliation. Declining utilization is seen, for multiple reasons, such as lack of awareness, insufficient expertise, or poor access to equipment. High level evidence for many types of palliative brachytherapy has been lacking. The objective of the current study was to review the evidence for utilization and efficacy of brachytherapy to palliate symptoms from cancer. MATERIALS AND METHODS: We performed a systematic search in EMBASE and MEDLINE for English-language articles published from January 1980 to May 2022 that described brachytherapy used for a palliative indication in adults with a diagnosis of cancer (any subtype) and at least one symptom related outcome. Individual case reports and conference abstracts were excluded. All publications were independently screened by two investigators for eligibility. RESULTS: The initial search identified 3637 abstracts of which 129 were selected for in-depth review. The number of studies (total number of patients) included in the final analysis varied widely by tumor site with the majority (68.2%) involving either lung or esophageal cancer. Despite a limited number of prospective trials that assessed the efficacy of brachytherapy for symptom management, there was a positive effect on palliation of symptoms across all tumor types. There was no clear trend in the number of publications over time. The most commonly cited symptom indications for palliation by brachytherapy were dysphagia, dyspnea, pain and bleeding. CONCLUSIONS: Brachytherapy can provide palliation for patients with advanced cancer, across different tumor sites and clinical scenarios. However, high level evidence in the literature to support palliative applications of brachytherapy is lacking or limited for many tumor sites. There appears to be a strong publication bias towards positive studies in favor of brachytherapy. Beyond anecdotal reports and individual practices, outcomes research can further our understanding of the role of brachytherapy in palliating advanced cancers of all types, and should be encouraged.

A Contouring Strategy and Reference Atlases for the Full Abdominopelvic Bowel Bag on Treatment Planning and Cone Beam Computed Tomography Images.

Purpose: To establish a practical contouring strategy with reference atlases for the abdominopelvic bowel bag on treatment planning computed tomography (TPCT) and cone beam computed tomography (CBCT) images. Methods and Materials: A scoping literature review was done to evaluate the existing definitions and contouring guidelines for bowel bag and small bowel planning-at-risk volume-like structures. A comprehensive definition was proposed for the abdominopelvic bowel bag that expanded the Radiation Therapy Oncology Group Pelvic Normal Tissue Consensus definition. Seven patients with TPCT and first-treatment-day CBCT images were selected from an institutional database to represent a range of normal anatomy and CBCT image quality. The TPCT and CBCT images were contoured using the proposed definition. During contouring, the Radiation Therapy Oncology Group definition's list of inclusion and exclusion structures was expanded. For areas with limited visibility of the bowel bag on either TPCT or CBCT, a set of operational definitions was developed based on consistently visible reference structures. Results: A literature review showed that previously existing bowel bag definitions predominantly focused on the pelvic region and did not provide a complete and practical description of the full abdominopelvic contour relative to structures consistently visible in all radiation therapy images. The proposed contouring strategy had 4 components: a definition, a list of inclusion and exclusion structures, 15 tabulated operational definitions, and a set of atlases. The bowel bag was defined as the peritoneal cavity and retroperitoneal duodenum and ascending and descending colon, as visualized at the time of image acquisition. The operational definitions formalized the location of the peritoneal fascial planes through a simple look-up table. The proposed contouring strategy and reference atlases were successfully used on both TPCT and CBCT images. Conclusions: This study produced a practical contouring strategy and reference atlases to enable reproducible delineation of the full bowel bag on TPCT and CBCT images. The strategy is a necessary first step toward consensus contouring with reduced observer variability, which is a prerequisite for evaluation of cumulative dose and its correlation with toxic effects, adaptive planning strategies, and automated contouring potential.

Development and validation of prognostic models for anal cancer outcomes using distributed learning: protocol for the international multi-centre atomCAT2 study.

BACKGROUND: Anal cancer is a rare cancer with rising incidence. Despite the relatively good outcomes conferred by state-of-the-art chemoradiotherapy, further improving disease control and reducing toxicity has proven challenging. Developing and validating prognostic models using routinely collected data may provide new insights for treatment development and selection. However, due to the rarity of the cancer, it can be difficult to obtain sufficient data, especially from single centres, to develop and validate robust models. Moreover, multi-centre model development is hampered by ethical barriers and data protection regulations that often limit accessibility to patient data. Distributed (or federated) learning allows models to be developed using data from multiple centres without any individual-level patient data leaving the originating centre, therefore preserving patient data privacy. This work builds on the proof-of-concept three-centre atomCAT1 study and describes the protocol for the multi-centre atomCAT2 study, which aims to develop and validate robust prognostic models for three clinically important outcomes in anal cancer following chemoradiotherapy. METHODS: This is a retrospective multi-centre cohort study, investigating overall survival, locoregional control and freedom from distant metastasis after primary chemoradiotherapy for anal squamous cell carcinoma. Patient data will be extracted and organised at each participating radiotherapy centre (n = 18). Candidate prognostic factors have been identified through literature review and expert opinion. Summary statistics will be calculated and exchanged between centres prior to modelling. The primary analysis will involve developing and validating Cox proportional hazards models across centres for each outcome through distributed learning. Outcomes at specific timepoints of interest and factor effect estimates will be reported, allowing for outcome prediction for future patients. DISCUSSION: The atomCAT2 study will analyse one of the largest available cross-institutional cohorts of patients with anal cancer treated with chemoradiotherapy. The analysis aims to provide information on current international clinical practice outcomes and may aid the personalisation and design of future anal cancer clinical trials through contributing to a better understanding of patient risk stratification.

The long term vaccine-induced anti-SARS-CoV-2 immune response is impaired in quantity and quality under TNFα blockade.

The humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in patients with chronic inflammatory disease (CID) declines more rapidly with tumor necrosis factor-α (TNF-α) inhibition. Furthermore, the efficacy of current vaccines against Omicron variants of concern (VOC) including BA.2 is limited. Alterations within immune cell populations, changes in IgG affinity, and the ability to neutralize a pre-VOC strain and the BA.2 virus were investigated in these at-risk patients. Serum levels of anti-SARS-CoV-2 IgG, IgG avidity, and neutralizing antibodies (NA) were determined in anti-TNF-α patients (n = 10) and controls (n = 24 healthy individuals; n = 12 patients under other disease-modifying antirheumatic drugs, oDMARD) before and after the second and third vaccination by ELISA, immunoblot and live virus neutralization assay. SARS-CoV-2-specific B- and T cell subsets were analysed by multicolor flow cytometry. Six months after the second vaccination, anti-SARS-CoV-2 IgG levels, IgG avidity and anti-pre-VOC NA titres were significantly reduced in anti-TNF-α recipients compared to controls (healthy individuals: avidity: p ≤ 0.0001; NA: p = 0.0347; oDMARDs: avidity: p = 0.0012; NA: p = 0.0293). The number of plasma cells was increased in anti-TNF-α patients (Healthy individuals: p = 0.0344; oDMARDs: p = 0.0254), while the absolute number of SARS-CoV-2-specific plasma cells 7 days after 2nd vaccination were comparable. Even after a third vaccination, these patients had lower anti-BA.2 NA titres compared to both other groups. We show a reduced SARS-CoV-2 neutralizing capacity in patients under TNF-α blockade. In this cohort, the plasma cell response appears to be less specific and shows stronger bystander activation. While these effects were observable after the first two vaccinations and with older VOC, the differences in responses to BA.2 were enhanced.

Multiple effects of TNFα inhibitors on the development of the adaptive immune response after SARS-CoV-2 vaccination

ObjectivesThe humoral immune response to SARS-CoV-2 vaccination in patients with chronic inflammatory disease (CID) declines more rapidly with TNF inhibition. Furthermore, the efficacy of current vaccines against Omicron variants of concern (VOC) including BA.2 is limited. Alterations within immune cell populations, changes in IgG affinity and the ability to neutralise a pre-VOC strain and the BA.2 virus were investigated in these at-risk patients. MethodsSerum levels of anti-SARS-CoV-2 IgG, IgG avidity and neutralising antibodies (NA) were determined in anti-TNF patients (n=10) and controls (n=24 healthy individuals; n=12 patients under other disease-modifying anti-rheumatic drugs, oDMARD) before and after the second and third vaccination by ELISA, immunoblot and live virus neutralisation assay. SARS-CoV-2-specific B-and T cell subsets were analysed by multicolour flow cytometry. ResultsIgG avidity and anti-pre-VOC NA titres decreased faster in anti-TNF recipients than in controls 6 months after the second vaccination (healthy individuals: avidity: p[≤]0.0001; NA: p=0.0347; oDMARDs: avidity: p=0.0012; NA: p=0.0293). Total plasma cell counts were increased in anti-TNF patients (Healthy individuals: p=0.0344; oDMARDs: p=0.0254), whereas absolute numbers of SARS-CoV-2-specific cells were comparable 7 days after vaccination. These patients had lower BA.2 NA titres compared to both other groups, even after the third vaccination. ConclusionsWe show a reduced SARS-CoV-2 neutralising capacity in patients under TNF blockade. In this cohort, the plasma cell response appears to be less specific and show stronger bystander activation. While these effects were observable after the first two vaccinations and with older VOC, the differences in responses to BA.2 were magnified. What is already known on this topicPatients with chronic inflammatory diseases treated with TNF inhibitors show a greater decrease in SARS-CoV-2 IgG 6 months after the second vaccination than patients taking oDMARDs and healthy individuals. What this study addsAntibodies from patients taking TNF blockers have a lower SARS-CoV-2 neutralising capacity and maturity. Plasma cells from these patients exhibit less specific immune reaction. SARS-CoV-2-specific T cells are less activated. Neutralisation against BA.2 is drastically reduced even after the third vaccination. How this study might affect research, practice or policyThis study emphasizes the need to protect vulnerable groups such as patients using TNF inhibitors. They could benefit from Omicron-adapted vaccination, but most likely they need to be protected by additional means other than vaccination.

Systematic review of health-related quality of life (HRQoL) issues associated with gastric cancer: capturing cross-cultural differences.

The treatment landscape for gastric cancer (GC) is constantly evolving with therapies affecting all aspects of health-related quality of life (HRQoL) which need careful monitoring. While there are HRQoL measures designed specifically to capture issues relevant to patients with GC, these might be outdated and only relevant to patients in westernised cultures. This review identifies the patient-reported measures used to assess HRQoL of patients with GC and compares the HRQoL measures used across cultures including East Asia, where GC is more prevalent. We conducted a systematic review of publications between January 2001 and January 2021. A total of 267 papers were identified; the majority (66%) of studies involved patients from East Asian countries. Out of the 24 HRQoL questionnaires captured, the European Organisation for Research and Treatment of Cancer Core Cancer measure (QLQ-C30) was the most widely used (60% of all studies and 62% of those involving patients from East Asian countries), followed by its gastric cancer-specific module (QLQ-STO22, 34% of all studies and 41% from East Asia). Eight questionnaires were developed within East Asian countries and, of the 20 studies including bespoke questions, 16 were from East Asia. There were six qualitative studies. HRQoL issues captured include diarrhoea, constipation, reflux, abdominal pain and abdominal fulness or bloating, difficulty swallowing, restricted eating, and weight loss. Psychosocial issues related to these problems were also assessed. Issues relating to the compatibility of some of the westernised measures within East Asian cultures were highlighted.