Palliative Radiotherapy Research Articles

A Prospective Longitudinal Study to Demonstrate the Utility of the Palliative Prognostic Index in Forecasting the Short-term Survival of Patients with Advanced Cancer in India

Objectives: In this study, our primary objectives were to validate the palliative prognostic index (PPI) tool in the context of palliative care for patients with advanced cancer. Specifically, we aimed to assess the accuracy of the PPI in predicting actual survival in these patients through prospective validation. Materials and Methods: To achieve our objectives, we enrolled a cohort of 227 advanced cancer patients receiving palliative care. The study population comprised 132 (58.1%) men and 95 (41.9%) women, with a median age of 52 years (Range: 20–81). Among them, 56 (24.7%) underwent chemotherapy, and 26 (11.5%) underwent palliative radiotherapy. We utilised the PPI score to categorise patients into three prognostic groups: (a) PPI score <4 indicating likely survival of more than 6 weeks; (b) PPI score 4–6 indicating likely survival shorter than 6 weeks; and (c) PPI score >6 indicating likely survival <3 weeks. Results: Through our analysis, we found that the PPI demonstrated limited predictive capabilities, particularly for short-term survival (<3 weeks). The PPI’s performance metrics included a positive predictive value of 45.24%, a negative predictive value of 100%, a sensitivity of 100.00% and a specificity of 88.94%. Conclusion: In conclusion, our study establishes the limited reliability of the PPI in predicting short-term survival (<3 weeks) among patients in palliative care with advanced cancer. These findings underscore the PPI’s potential as a valuable tool for healthcare professionals, aiding in the development of treatment plans and facilitating discussions on end-of-life care options with patients and their families. In addition, the PPI may assist healthcare professionals in identifying individuals who could benefit from more aggressive interventions or those approaching the end of life, thereby guiding the provision of additional support and care.

EXPRESS: Radiation therapy in combination with immune checkpoint inhibitors in metastatic lung cancer: Effect of fractionation.

Immunotherapy with checkpoint inhibitors has improved the outcomes of patients with metastatic lung cancer in recent years. Despite improved prognosis, not all patients respond to treatment. Therapeutic interventions to build on the success of immune checkpoint inhibitors are needed. A retrospective review of patient records for patients who had received immune checkpoint inhibitors in a single cancer center over four years was undertaken. Demographic and disease characteristics of patients with metastatic non-small cell lung cancer were recorded. Data on other treatments including chemotherapy and radiation therapy were extracted, and survival outcomes were calculated. Most (81.8%) of the 77 metastatic lung cancer patients examined had received palliative radiation therapy within three months of starting immune checkpoint inhibitors. While the survival outcomes of these patients did not differ from patients who had not received radiotherapy, patients who had undergone hypofractionated radiotherapy (defined as one or more fractions of 700 cGy or higher) displayed a better overall survival (OS) than the rest of the cohort. Palliative radiation therapy administered in proximity with immune checkpoint inhibitors immunotherapy had no effect on the OS of metastatic lung cancer patients. However, patients receiving palliative radiotherapy with fractions above 700 cGy showed better OS. Further studies are needed to optimize a combination strategy.

OGC SO06 - Novel Non-metallic Fiducial marker for Radiotherapy in Oesophageal Cancer

Abstract Background Early oesophageal tumours are technically difficult to delineate on the planning computed tomography (pCT) for Image Guided Radiotherapy (IGRT). We describe the use of a novel non-metallic fiducial marker for this purpose. Method Non-metallic fiducial marker (NFM) (BioXmark) was used in 17 patients from April 2021 to November 2022 for marking tumour site prior to radical or palliative radiotherapy. NFM was injected in the sub-mucosal plane using fluoroscopy under general anaesthesia, with the patient supine and using regular injection catheter and syringes. After the initial series, further modifications to the technique improved the injection and shortened operative time. These include left lateral positioning, an ultra-fine injection catheters and micro-dosing syringes. Feedback from the treating radiation oncologists was sought for all the patients. Results Injection was successful in all the patients. In the initial series before the modifications to the technique, often the marker was a larger than anticipated due to a combination of poor visibility when the patients were supine and use of larger bore injection catheters. Once the patient position was changed along with the changes in the injection catheters and the syringes, marking was very precise. Conclusion Previously used fiducial markers are gold based. While these were visible on pCTs, they are known to cause distortion along with being expensive and cumbersome to inject. In comparison, NFM is easy to inject without the artefacts seen with metallic markers. We refined the technique further by changing the patient’s position to left lateral which afforded a improved fluoroscopic visibility. Introducing finer injection catheters and micro-dosing syringes further led to usage of lesser volume and precise marking respectively. In summary we present a series of patients whose early oesophageal tumours were marked with a NFM aiding precise delivery of radiotherapy.

Respiratory-gated proton beam therapy for intrahepatic cholangiocarcinoma without fiducial markers.

Intrahepatic cholangiocarcinoma (ICC) is a challenging primary liver cancer with a poor prognosis, especially in unresectable cases. Traditional palliative irradiation is limited in reducing liver doses. This study aimed to evaluate the efficacy and toxicity of respiratory-gated proton beam therapy without fiducial markers for intrahepatic cholangiocarcinoma. Between October 2011 and February 2022, 24 patients (median [range] age, 71 [41-88] years) were evaluated at our institution. Twelve patients were pathologically diagnosed with ICC. All patients underwent respiratory-gated proton beam therapy at a dose of 48-83.6 (relative biological effectiveness) in 20-38 fractions with four-dimensional computed tomography planning. The median follow-up period was 18.5 (range, 2.0-74.0) months. The median tumor size was 41 (range, 10-134) mm. Twenty-one patients were classified as having Child-Pugh class A, and three patients were classified as having Child-Pugh class B. Local progression was defined as any growth of the irradiated tumor. The median survival time was 28months for all patients. The Kaplan-Meier estimates of the 2-year overall survival, progression-free survival, and local tumor control rates were 51%, 26%, and 73%, respectively. Local tumor control rates were non-inferior to those reported in previous studies using fiducial markers. One patient had grade 4 pleural effusion; however, whether this was an adverse event due to the proton beam therapy was unclear. Respiratory-gated proton beam therapy without fiducial markers is an effective and less invasive treatment option for ICC, showing potential for improved local control and tolerable adverse effects.

Efficacy of palliative hemostatic radiotherapy for tumor bleeding and pain relief in locally advanced pelvic gynecological malignancies.

The appearance of symptomatic tumor-related vaginal bleeding and pain in advanced incurable cancer patients with pelvic gynecological malignancies remains atherapeutic challenge in oncological treatment. The aim of our analysis was to evaluate the efficacy and safety of palliative hemostatic radiotherapy. We retrospectively identified patients who had received palliative hemostatic radiotherapy (RT) at our institution between 2011 and 2023 and evaluated acute toxicity, local control, cessation of bleeding, and pain relief. In total, 40patients with amedian planning target volume of 804 cm3 were treated with amedian total dose of 39 Gy in 13fractions, resulting in 6‑month and 1‑year local control rates of 66.9 and 60.8%, respectively. No higher-grade (>gradeIII) acute RT-induced toxicity appeared. Complete cessation of bleeding was achieved in 80.0% of all patients after amedian of 16days and pain relief was documented in 60.9% at first follow-up. 37.5% of the women required ablood transfusion and 25% an additional tamponade with local hemostatic agents. Successful stopping of bleeding was significantly less frequent in patients receiving anticoagulation concurrently with radiation and in the case of infield re-irradiation. Patients with ahigher total RT dose had cessation of bleeding significantly more often, with acut-off value of at least EQD2 (α/β = 10) = 36 Gy. The applied RT technique and planning target volume had no significant influence on the occurrence of bleeding cessation. Palliative hemostatic radiotherapy for locally advanced pelvic gynecological malignancies is safe and effective in achieving high control rates of hemostasis in tumor bleeding and pain relief.

A case series and review of stereotactic body radiation therapy for contiguous multilevel spine metastases.

A majority of published series report on stereotactic body radiation therapy (SBRT) for 1-2 contiguous vertebral levels due to concerns regarding setup accuracy and radiation toxicity. This study evaluates patients with metastases spanning ≥ 3 contiguous levels treated with SBRT and augments its findings with a review of other studies investigating multilevel spine SBRT. Analysis of a prospectively collected database of 49 patients with 55 metastases spanning ≥ 3 contiguous vertebral levels treated with SBRT at a single institution (2002-2023) was performed. Outcomes identified included local failure (LF), pain response, overall survival, and toxicity. The median single-fraction prescription dose was 15Gy (range: 8-18); multifractionated treatment utilized prescription doses of 18-30Gy in 2-5 fractions. Median follow-up was 7 months (range: 1-103). The 6-month, 1-year, and 2-year cumulative incidence rates of LF were 7%, 11%, and 11%, respectively. No prognostic factors were associated with LF. Pain was reported to improve or remain stable for 49 lesions (89%). Ten adverse radiation events (18%) were identified; pain flare (5%), dermatitis (4%), and vertebral compression fracture (VCF, 9%). The 3-month, 6-month, and 1-year cumulative incidence rates of VCF were 4%, 7%, and 7%, respectively. No instances of esophageal toxicity or myelopathy were observed. This study of multilevel SBRT is one of the largest to investigate outcomes in this challenging clinical scenario. Spine SBRT confers low rates of LF and toxicity for patients with multilevel disease, which was previously considered a relative contraindication. Spine SBRT may be considered in this patient population instead of low-dose palliative RT.

Efficacy and tolerance of short cycles of palliative radiotherapy in advanced anal sac adenocarcinomas in dogs

Successful management of advanced anal sac gland adenocarcinomas (AGASACA) often requires a multimodal approach. In recent years the role of palliative radiotherapy (pRT) has become increasingly more important, mainly in dogs with severe local clinical signs. This study describes efficacy and tolerance of short cycles of pRT. Retrospective single-institution study including dogs with AGASACA treated with at least one short cycle of pRT (IMRT, 4Gy BID for two consecutive days). All dogs were staged with CT and followed to death. Outcome measures were PFS and OST from the first pRT. Potential prognostic factors were evaluated. Twelve dogs were included (one stage II, four stage III, seven stage IV). Three dogs had one cycle, seven had two cycles, and two had three cycles of pRT. All dogs experienced a clinical benefit after pRT. One dog also had surgery, four systemic treatment, and five both. Eleven dogs died during the follow-up (four for local progression, six for systemic progression, one unknown). The median PFS was 198 days (95% CI 98—298) and the OST was 250 days (95% CI 124—376). Mild, acute, short-term GI toxicity occurred in seven dogs (five G1; two G2). None of the dogs experienced clinically relevant late toxicity. Short cycles of radiotherapy can be effectively used as a palliative treatment for advanced AGASACA with minimal toxicity. The small number of patients did not allow to assess the benefits of combining RT with other treatment modalities or the identification of meaningful prognostic factors.

Outcomes After Palliative Radiotherapy in Patients with Symptomatic Locoregionally Advanced Breast Cancer.

Symptomatic locoregionally advanced breast cancer (SLABC) can cause troublesome pain or wound complications that negatively impact quality of life. Although palliative radiotherapy (RT) can minimize tumor-related symptoms, how best to tailor RT to achieve the most meaningful and durable response is not well defined. This is a single-institution, multi-site retrospective review of patients with SLABC treated between 2016 and 2023 with palliative RT to symptomatic disease in the breast, chest wall, and/or regional lymph node basins. Overall survival (OS), locoregional control (LC), clinical and radiographic treatment response, overall pain scores, and treatment-related toxicities were analyzed. 164 patients with a median age of 57 years were analyzed with a median follow-up time of 4.97 months. 86% had distant metastases. The most common presenting symptom was pain (87%), followed by ulcerating or fungating lesion (76%) and discharge (45%). The median cumulative biologically effective dose to the gross tumor volume (BEDGTV) was 69 Gy. The 1-year OS and LC rates were 37% and 63%, respectively. Eighty-one percent experienced improvement in symptoms within 3 months after RT, the odds of which increased per Gy BEDGTV (OR 1.029, p=0.003). Acute toxicities were associated with number of fractions and BEDGTV (both p<.001), but not with concurrent systemic therapy nor reirradiation (both p>.05). Trends in pain scores showed a significant change in pain trajectory that was sustained during the first year after RT. OS and LC were not different among patients who received 1 vs 2-10 vs >10 fractions, and between ≤70 vs >70 Gy BEDGTV. In this large series of patients with SLABC, palliative RT was effective at relieving locoregional symptoms with acceptable toxicity, with the likelihood of symptom improvement associated with radiation dose. Survival of these patients remains poor, highlighting the importance of palliative care strategies that minimize overall symptom burden while maximizing quality of life.

Optimum radiation dose for palliation in head and neck squamous cell carcinoma (OpRAH) – A phase 3 randomized controlled trial

PurposeRadiotherapy is frequently employed for palliative treatment in locally advanced head and neck squamous cell carcinoma (HNSCC) but radiation dose fractionation regimens are not well-defined. We designed this phase 3 randomized controlled trial to compare two weekly hypo fractionated regimes and study the effect on progression-free survival (PFS) in this subset of patients. Materials and MethodsNon-metastatic locally advanced HNSCC patients (n = 305) who were not suitable for curative treatment were randomized to Arm A (20 Gy/5#/5 days) and Arm B (30 Gy/5#/5 days). PFS and OS were recorded along with acute toxicity using patient-reported quality of life HN QLQ 43. ResultsFrom April 2020 to August 2023, 390 patients were randomized, of which 305 were eligible for final analysis. At a median follow-up of 13.9 months, PFS and median overall survival (OS) for the entire cohort was 7.4 and 10.03 months, respectively. PFS (p-0.553) and OS (p-0.203) did not differ significantly between the two groups. Toxicity rates were similar between the two arms and dose escalation was well tolerated. Patients with a better PS were found to have significantly better OS. No significant benefit in OS or PFS was observed in patients who received neoadjuvant chemotherapy (NACT), underwent definitive conversion, or received palliative chemotherapy at progression. ConclusionThis is the largest phase 3 RCT to analyze the safety and efficacy of weekly palliative radiotherapy regimens and has not demonstrated further improvement with dose escalation

Prognostic Value of Sarcopenia in Elderly Patients with Metastatic Non-Small-Cell Lung Cancer Undergoing Radiotherapy

Background: Sarcopenia, a syndrome characterized by age-related loss of muscle mass and function, lacks universally accepted diagnostic criteria, particularly for its role as a prognostic factor in elderly patients with non-small-cell lung cancer (NSCLC). This study aimed to evaluate the prognostic significance of sarcopenia, assessed by psoas muscle size on baseline CT scans, in patients over 70 years of age with metastatic NSCLC. Methods: We retrospectively analyzed 85 elderly patients undergoing palliative radiation therapy between August 2022 and July 2024. Using morphometric analysis of psoas size, we investigated its correlation with overall survival (OS) and progression-free survival (PFS). Results: Our results showed that decreased psoas size was significantly associated with shorter OS and PFS, with median OS of 10 months and PFS of 4 months in sarcopenic patients compared to longer survival times in non-sarcopenic patients. Median survival of non-sarcopenic vs. sarcopenic patients was 21 ± 7 months (muscle area &gt; median) versus 5 ± 2.3 months (muscle area &lt; median). Multivariate analysis confirmed that psoas size, along with ECOG performance status and treatment of primary NSCLC, was a significant predictor of survival. Discussion: These findings suggest that psoas muscle size is a valuable prognostic marker for elderly NSCLC patients, potentially guiding treatment decisions and patient management. Further research is needed to validate these results and refine prognostic models for this population.

FROM VEIN TO BRAIN: ENHANCING TRAffiCKING OF CAR T-CELLS IN DIFFUSE MIDLINE GLIOMA

Abstract AIMS H3K27M-altered diffuse midline glioma (DMG) is the deadliest childhood brain tumour, with treatment limited by anatomical location and chemoresistance; palliative radiotherapy remains the mainstay of treatment. Chimeric antigen receptor (CAR) T-cell therapy produces promising pre-clinical results in treating these tumours whilst leaving interspersed normal brain cells intact. Early clinical outcomes of GD2-CAR T-cell therapy for H3K27M-altered DMG demonstrate short-lived neurological and radiological improvement. Enhancing trafficking to and infiltration into the tumour core may enhance CAR T-cell efficacy. Here, advanced T-cell engineering modules are tested for their ability to improve CAR T-cell trafficking. METHOD A library of T-cell engineering modules was created each with a unique DNA barcode to allow identification of CAR T-cells expressing a given module. The library includes chemokine receptors (CCR) to improve tumour homing by chemotaxis towards tumour-secreted chemokines, adhesion molecules to increase extravasation across the blood-brain-barrier, and molecules to degrade upregulated tumour extracellular matrix (ECM) components to improve CAR T-cell motility through the tumour. Murine T-cells were co-transduced with a CAR and barcoded advanced T-cell engineering modules and administrated intravenously in syngeneic models of high-grade glioma (HGG)/DMG. Tumour, normal brain, bone marrow, spleen and liver tissue were collected at several time points post CAR T-cell administration to assess presence of CAR T-cells using genetic barcodes. RESULTS Co-expression of advanced T-cell engineering modules did not impair CAR T-cell function in vitro. CARs co-expressing selected CCRs were preferentially detected in tumour tissue in mice with GL261-EGFRvIII or H3.3K27Mp53LOFPDGFRAWT-engrafted tumours. Findings were further validated by flow cytometry detection of selected CCR-expressing CAR T-cells as compared to CAR T-cells without additional engineering components. Similar experiments for adhesion molecules and ECM modifiers are planned. CONCLUSION Results to date indicate that CAR T-cells co-expressing selected CCRs enhance their homing to HGG/DMG tumours, encouraging further in vivo research to assess impact on CAR T-cell efficacy.

Hypofractionated versus standard fractionation radiotherapy for merkel cell carcinoma

Purpose/Objective(s)Merkel cell carcinoma (MCC) radiation treatment has historically consisted of standard 1.8–2 Gy fractions treated daily over 4–6 weeks. Hypofractionated treatment regimens have demonstrated tumor control and toxicity equivalence to standard fractionation regimens for common cutaneous malignancies such as basal cell and squamous cell carcinomas. Herein we report the outcomes of hypofractionated versus standard fractionation radiotherapy for MCC at our institution.Materials/MethodsThe study involved a retrospective review of MCC patients treated with radiotherapy. Treatment characteristics and patient outcomes, including acute toxicities, disease recurrence and survival data were collected. The cumulative incidence of local and distant failures was estimated, with death as a competing risk.ResultsA total of 29 treatment courses for 24 patients were included, of which 13 involved standard fractionation with curative intent, 10 involved hypofractionated radiotherapy with curative intent, and 6 involved single fraction (8 Gy) palliative radiation. Half the patients were treated to a head/neck site. A subset of patients treated adjuvantly with curative intent included 8 standard fractionation and 8 hypofractionated radiotherapy patients. No statistically significant differences in local and/or distant failure or overall survival was observed between the patient groups.ConclusionHypofractionated radiotherapy for MCC was associated with similar treatment outcomes relative to standard fractionation. In our limited patient sample, hypofractionated radiation treatment achieved similar results with similar toxicity and fewer treatments. Further analysis of a larger patient population with longer follow up is needed to confirm treatment tolerability and efficacy.

Effectiveness of radiotherapy in delaying treatment changes in primary or secondary immunorefractory oligoprogressive patients: preliminary results from a single-center study.

To investigate whether the addition of radiotherapy could be an appropriate option to delay the time-to-next systemic treatment (TTNsT) in patients with oligoprogressive solid tumors who had acquired or innate resistance to immune checkpoint inhibitors (ICIs). Patients with oligoprogressive disease treated with ICIs and radiotherapy at our Institute from January 2019 to June 2023 were retrospectively identified. Patients were stratified as primary or secondary immunorefractory according to the time of onset of ICI resistance. TTNsT and Time-To-Resistance (TTR) were the primary outcomes. Secondary outcomes included: post-radiotherapy first progression-free survival (pR-PFS), Local Control (LC), Overall Survival (OS), and treatment-related toxicities. In addition, out-of-field effects (such as the abscopal effect) of radiotherapy have been hypothesized. The survival rates were analyzed using the Kaplan-Meier method and long-rank test. 40 out of 105 screened patients with oligoprogressive disease met the inclusion criteria. Of these, 28 had an acquired drug resistance while 12 had an innate drug resistance. Radiotherapy was offered as a local treatment approach in all patients. RT techniques were classified into three regimens: standard palliative hypofractionated radiotherapy (hypo-RT), stereotactic radiotherapy (SRS/SBRT), and lattice radiotherapy (LRT). After a median follow-up of 22.5months, the median TTR was 4months (range 3-4) in patients with innate resistance vs 14months (range 7-36) in patients with acquired resistance. Median TTNsT among patients with acquired and those with innate resistance was not reached (NR) vs 24months (range 7-72). Overall, only six patients suffered from a local failure. Although out-of-field effects of radiotherapy were hypothesized, we were unable to record them as they did not occur during the observation period. Regardless of the radiation dose, there was no observable ≥ Grade 2 acute or late treatment-related toxicity. Our preliminary results seem to confirm that the integration of radiotherapy and ICIs may allow for the continuation of systemic therapy beyond progression, which can have a subsequent benefit in terms of survival outcomes even in patients with innate resistance.

8105 Radiation-Induced Hyperthyroidism in the Context of Palliative Radiation Therapy

Abstract Disclosure: A. Randhawa: None. G. Palaguachi: None. J.G. Karam: None. Introduction: Palliative radiotherapy, designed to alleviate focal symptoms in advanced, incurable cancer, aims to enhance quality of life with minimal treatment burden. The thyroid gland's susceptibility to neck radiation is known, primarily leading to hypothyroidism. However, hyperthyroidism is a much less frequently reported adverse effect that is poorly understood. This case report highlights an unusual instance of radiation-induced hyperthyroidism. Case Presentation:The patient is a 53 years-old woman with history of Ewing’s sarcoma of the sacrum diagnosed in August 2022, treated initially with chemotherapy (cyclophosphamide, vincristine, etoposide and ifosfamide), but diagnosed with leptomeningeal metastasis and T12/L1 mass in October 2023 when she presented with lower extremities weakness and urinary incontinence. She underwent T12-L1 laminectomy, resection of tumor and fusion, and was started on palliative intent radiation therapy for the brain and C-spine. A month later, she was admitted for altered mental status and was found to be persistently tachycardic at 140 bpm. Thyroid function testing was sent and revealed hyperthyroidism with TSH of 0.07 mIU/L (0.39-4.08), Free T4 of 1.74 ng/dl (0.58-1.64), T4 of 10.7ug/ml (4.4-9.5), T3 of 0.54 ng/ml (0.72-1.35), with undetectable Thyroid Peroxidase Antibodies and Thyroid Stimulating Immunoglobulin level. Thyroid Ultrasound showed a small and homogenous thyroid gland with no discrete nodules. Radioactive Iodine uptake and scan was not obtained because of exposure to iodized contrast during hospital stay. The patient had no available baseline thyroid function tests. She had no recent fever or viral illness. Unfortunately, her clinical condition deteriorated rapidly, and she passed away on the seventh day of admission. Conclusion: While hypothyroidism is a well-established consequence of high-dose irradiation, the mechanisms behind the rarer radiation-induced hyperthyroidism remain unclear. Speculation includes the release of autoantigens from damaged thyroid glands, triggering an immune response and potentially leading to Graves' hyperthyroidism. However, our case more likely represents a hyperthyroid phase in the triphasic sequence of destructive subacute thyroiditis, given the absence of elevated thyroid antibodies, thyroid nodules, and other causes of thyroiditis. Increasing awareness of radiation-induced hyperthyroidism, unraveling its mechanisms, and refining diagnostic strategies such as obtaining baseline and monitoring thyroid function testing are crucial, particularly in the context of palliative therapy, where striking the delicate balance between efficacy and minimizing toxicity is paramount. Presentation: 6/3/2024

6702 Management And Complications Of Metastatic Adrenocortical Carcinoma Presenting With Severe Cushing Syndrome

Abstract Disclosure: S. Rodrigues: None. A.K. Sumal: None. Background: Metastatic adrenocortical carcinoma (ACC) presenting with Cushing syndrome (CS) is a complicated, aggressive disease that commonly requires multiple adrenal steroidogenesis inhibitors and chemotherapy to achieve hormonal and tumor control. Clinical Case: A 66-year-old man with a history of prostate cancer and hypertension presented with right flank and back pain, worsening type 2 diabetes, profound proximal muscle weakness, and 3+ lower extremity edema to his thighs. CT and PET-CT revealed a 10.9 cm right adrenal mass with pericaval lymphadenopathy and metastatic disease at the L2 vertebral body. Laboratory testing demonstrated evidence of hypercortisolism with elevated 24-hour urinary cortisol excretion (449 mcg/24h; n&amp;lt;45 mcg/24h), and abnormal 1 mg dexamethasone suppression test (cortisol 15 mcg/dL; n&amp;lt; 1.8 mcg/dL) with suppressed ACTH (&amp;lt;6 pg/mL; n=7-63 pg/mL). Surgical resection of the primary tumor was aborted intraoperatively given the discovery of new peritoneal metastases, which were confirmed by biopsy to be metastatic ACC. He was started on mitotane and osilodrostat to manage his severe CS. He was also started on dexamethasone, both to prevent adrenal insufficiency and to avoid influencing serum cortisol measurements used to assess disease control. However, given his significant peripheral edema and weakness, he was functionally unable to receive chemotherapy. Despite rapid uptitration of mitotane and osilodrostat over three weeks, his CS remained uncontrolled, and he was ultimately hospitalized for lower extremity paralysis and septic shock due to pyelonephritis. Repeat imaging revealed severe spinal canal stenosis from an L2 pathologic fracture, as well as worsening hepatic, osseous, peritoneal, and retroperitoneal metastases. After recovery from his septic shock, he was started on chemotherapy with carboplatin and etoposide while hospitalized, but his mitotane was intermittently held due to elevated transaminases. His hospital course was complicated by hypotension requiring pressor support, atrial fibrillation, hemoperitoneum, worsening anasarca, and acute kidney injury requiring continuous renal replacement therapy. Given his worsening condition that precluded him from further chemotherapy or palliative radiation, he elected to pursue comfort care measures and expired shortly thereafter. Conclusion: This case highlights the therapeutic challenges of metastatic ACC presenting with life-threatening CS. Simultaneous use of multiple adrenal steroidogenesis inhibitors is often required for control of hypercortisolism, and chemotherapy is equally necessary to manage tumor burden. However, as in this case, disease-related complications can limit treatment management and result in rapid deterioration. Thus, early diagnosis and prompt treatment of metastatic ACC presenting with CS is critical to prevent morbidity and mortality. Presentation: 6/3/2024

6918 A Unique Case of Oncocytic Thyroid Cancer with an NBN Gene Pathogenic Variant

Abstract Disclosure: A. Grover: None. S. Jhawar: None. S. Shekhar: None. S.A. Avadhanula: None. G. Al-Naqeeb: None. G. Thota: None. P. Veeraraghavan: None. C. Cochran: None. M.Y. Kao-Hsieh: None. A. Gharib: None. F.E. Escorcia: None. J. Del Rivero: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None. Introduction: Oncocytic thyroid carcinoma (OTC), previously known as “Hürthle cell” carcinoma, makes up less than 5% of all thyroid cancers. OTCs are often aggressive with a high risk of metastasis, and a poorer prognosis compared to other forms of differentiated thyroid carcinoma (DTC). Molecular drivers of OTC include pathogenic variants (PVs) in NRAS, DAXX, CDKN1A, the mitochondrial genome and chromosomal alterations. PVs in the NBN gene in OTC have not been previously reported. Case: A 53-year-old male was noted to have a thyroid nodule on a routine physical examination. Patient denied any hyper/hypothyroid or compressive symptoms, and family history was unremarkable. Cytopathologic analysis of the fine needle aspiration biopsy of the nodule was consistent with a thyroid follicular neoplasm (Bethesda IV). A total thyroidectomy with central compartment neck dissection was performed. Histopathologic examination demonstrated a 7 cm x 4 cm x 4 cm OTC with capsular and lymphovascular invasion, but without extra-thyroidal extension or lymph node metastasis (pT3aN0Mx). Subsequently, adjuvant radioiodine (RAI) I131 therapy with 165 mCi was administered and post-therapy scan revealed neck uptake. One-year post-therapy RAI diagnostic scan was negative. Three years following the initial thyroid surgery, elevated serum thyroglobulin (Tg) levels were noted. A computed tomogram of the chest revealed multiple bilateral lung nodules. Further imaging ruled out involvement of other distant sites. A diagnostic lower lung wedge resection demonstrated metastatic OTC. The tumor stained positive for CK7, PAX8, TG, TTF-1 and negative for CK20 on immunohistochemistry. Next-generation sequencing of the tumor tissue (Oncomine Comprehensive Assay v3) revealed a PV in the NBN gene (c.2166_2167delGCinsAT; p.Trp722Ter). A year later, the serum Tg levels continued to rise, and the lung nodules had increased in size. Due to disease progression, lenvatinib was initiated. A [F18]-fluorodeoxyglucose positron emission tomography performed one year later demonstrated persistent pulmonary tumor burden with new osseous metastasis in the right scapula, left acetabulum, and the sternum. Zoledronic acid was initiated for the treatment of the skeletal metastases, and palliative external beam radiation (2000 cGy in 5 fractions) was administered to the sternal lesion to alleviate the bone pain. Conclusion: The NBN gene encodes for the protein nibrin, a member of the MRE11/RAD50 complex that is involved in DNA repair. PVs in NBN are commonly identified in non-thyroidal malignancies such as breast and lung carcinomas. While NBN PVs are rarely reported in DTCs, as per our knowledge, this is the first described case of OTC with a PV in NBN as the molecular driver, manifesting with an aggressive disease course. Identification of this novel PV therefore adds to the current knowledge of the molecular landscape of OTC. Presentation: 6/3/2024

8791 A Case of Hyperfunctioning Thyroid Nodules Evaluated for Thyroid Metastasis in the Setting of Oropharyngeal Squamous Cell Carcinoma

Abstract Disclosure: M. Alashoor: None. J. Gogineni: None. A. Bakar: None. Introduction: Identifying and evaluating hyperfunctioning thyroid nodules in the setting of metastatic head and neck cancers represents a diagnostic challenge that may result in inaccurate identification of perithyroidal lymph node metastasis as malignant or metastatic thyroid nodules with standard workup. Case presentation: A 72-year-old male with a history of stage IV metastatic oropharyngeal squamous cell carcinoma, metastasized to the lymph nodes, lungs, mediastinum, and bilateral iliac bones. He was diagnosed two years ago and received chemotherapy, maintenance immunotherapy with pembrolizumab, and targeted palliative radiation therapy, with good clinical response. Restaging PET-CT two years later revealed local progression. During his workup, he was noted to have persistently abnormal thyroid function test with low TSH (0.03​​µIU/mL, n 0.3-5.33), normal free T4 (0.97ng/dL, n 0.60 - 1.40), mildly elevated free T3 (3.91pg/mL, n 2.5-3.9), negative thyrotropin receptor antibodies levels, negative TSI, negative TPO antibody, noted evidence of subclinical hyperthyroidism consistent over the past year. Radioactive iodine uptake demonstrated multinodular gland, mildly elevated 24-hour uptake of 28% consistent with hyperthyroidism, with decreased activity in the left lobe. Thyroid ultrasound revealed multiple probable malignant thyroid nodules, a 1.8 cm TI-RADS 5 lesion of the deep margin of the lower pole of the right lobe, and a 1.6 cm TI-RADS 5 lesion of the upper pole on the right lobe. He was treated with methimazole 5 mg. Further workup with fine needle aspiration demonstrated the right upper lobe nodule sample was positive for squamous cell carcinoma, findings suspicious for metastasis. He subsequently proceeded with radical tonsillectomy, right neck dissection, and right hemithyroidectomy. Surgical pathology results noted, right neck metastatic HPV-associated squamous cell carcinoma involving the lymph nodes with extranodal extension, right oropharyngeal HPV-mediated squamous cell carcinoma. The thyroid gland biopsy was significant for incidental papillary microcarcinoma 2mm, thyroid follicular nodular disease, without evidence of squamous cell carcinoma or metastatic infiltration. Post-hemithyroidectomy, his thyroid function normalized, and methimazole was discontinued. Conclusion: Thyroid metastasis from head and neck cancers represent a rare entity. In patients with a history of malignancy, evaluation of new thyroid masses remains crucial. While FNA is a sensitive method for detecting thyroid metastases, inaccuracies may occur, impacting the identification of thyroid nodules in the presence of local metastatic lymphadenopathy. Identifying squamous cell carcinoma in the thyroid can significantly influence the treatment plan of patients with metastatic carcinomas, therefore careful consideration must be undertaken on evaluation. Presentation: 6/1/2024

Outcomes of Palliative RT to Liver in Liver Metastases

Introduction: Various techniques are available to treat and alleviate pain and other symptoms in liver metastasis (LM) or advanced hepatocellular carcinoma (HCC) patients. One of such technique is the external beam radiotherapy to whole liver. This study aimed to evaluate the feasibility, efficacy, tolerability and patient’s reaction to external beam radiotherapy (EBRT) in palliation of symptoms and quality of life (QoL) LM patients or HCC patients. Material and Method: A total of 50 patient of either liver metastasis or HCC were included and planned on single 8Gy/fraction to whole liver radiotherapy. Ultrasonographic guided marking of liver was done prior to treatment and pretreatment dexamethasone and antiemetic was given. Evaluation was done at 1 week and 1 month after the end of treatment. Results: After the whole liver radiotherapy, significant improvement was reported in the bilirubin level (68%), pain level (75.5%), and nausea (32%). Talking about the quality of life, the radiotherapy was reported to found potentially effective in enhancing the quality of life among the patients. Greatest percentage improvementwas reported for pain (75.6%), Global health status (39.6%), physical functioning (32.4%), rolefunctioning (36%), social functioning (36%) and appetite loss (30.6%).

Hypofractionated Radiotherapy for Breast Cancer: Experience of the Radiotherapy Department of the Mali Hospital

Aim: To evaluate the outcomes of hypofractionated radiotherapy in breast cancer. Patients and Methods: It was a retrospective study over a 3-year period, from January 2016 to December 2018, of breast cancer patients treated with hypofractionated radiotherapy at Mali Hospital. All patients with histologically confirmed breast cancer without distant metastases were included. We excluded all patients treated for breast cancer with palliative or normofractionated radiotherapy, patients with metastatic disease on admission and incomplete records. Patients were classified according to the 7th edition TNM classification. Radiotherapy was administered using an Elekta Compact 6MV linear accelerator with the 3D conformal technique, at a total dose of 42 Gy at a rate of 2.8Gy/fraction in 15 sessions, and 5 sessions/week. Data were collected from medical records and treatment sheets, entered into Excel and analysed using SPSS version 23 software. Results: Sixty-four patients out of 129 met our selection criteria (49.61%). The mean age was 44.65+/-11.11 with extremes of 25 and 88 years. Previous hormonal contraception was found in 23.43% of cases, familial breast cancer in 6.25% and nulliparity in 4.68% of cases. Ultramammography was performed in all patients. Assessment of distant extension consisted of a thoraco-abdominal CT scan in 92.18% of cases, and abdominal ultrasound combined with a chest X-ray in 7.82% of cases. Histology of the biopsy specimen showed non-specific carcinoma in 96.87% of cases, Scarf-Bloom and Richardson (SBR) grade II in 64.81% and grade III in 27.78%. Immunohistochemistry was performed in 26 patients, hormone receptor positive in 57.69% (n=15) and triple negative in 42.31% (n=11). Patients were classified as stage T3 or T4 in 82.68% of cases. 95.4% of patients underwent mastectomy and 4.6% lumpectomy; all patients underwent axillary curage. The patients were treated with hypofractionated radiotherapy on the wall and the supra- and sub-clavicular lymph

Improved outcomes of palliative radiotherapy combined with immune checkpoint inhibitors in recurrent or metastatic cervical cancers

BackgroundImmunotherapy provides a remarkable survival advantage for patients with recurrent or metastatic cervical cancer (R/M CC). However, the role of immunotherapy in combination with radiotherapy in R/M CC remains unclear. MethodsWe retrospectively analyzed factors affecting immunotherapy effectiveness in patients with R/M CC. Clinical outcomes including tumor response and patient survival were assessed. Kaplan-Meier curves with the log-rank test were employed to compare survival data. Cox regression analysis was utilized to investigate prognostic factors. ResultsA total of 65 R/M CC patients treated with immune checkpoint inhibitors were eligible for analysis. We found that immunotherapy combined with palliative radiotherapy showed a significant positive correlation with complete response (OR = 6.31; 95 %CI: 1.74–22.91; p = 0.005). The 36-month progression-free survival (PFS) rate (73.7 % vs 33.8 %, p = 0.0048) and 36-month overall survival (OS) rate (85.7 % vs 38.7 %, p = 0.0043) were also prominently increased. We further demonstrated that patients prolonged 36-month PFS rate (69.9 % vs 15.2 %; p < 0.001) and 36-month OS rate (64.6 % vs 39.7 %; p = 0.032) when they had more than 4 cycles of immunotherapy. Meanwhile, our findings showed that patients with only recurrence had longer 36-month OS rate (77.7 % vs 44.4 % vs 40.1 %; p = 0.024) compared to those with only metastasis and both. We also observed that patients with squamous carcinoma had higher 2-year PFS rate (57.9 % vs 14.6 %; p = 0.042) than those with other pathological subtypes (adenocarcinoma, adenosquamous carcinoma and neuroendocrine carcinoma). ConclusionsThe combination of immunotherapy and palliative radiotherapy increased complete response rates and improved survivals in recurrent or metastatic cervical cancer patients.