Prior Radiation Research Articles

Clinical Factors Associated with Suspicious 18F-DCFPyL PSMA PET Activity in Patients Initially Managed with Radical Prostatectomy including PSA

There is limited data on PSMA PET/CT for work-up of recurrence after radical prostatectomy (RP) at low PSA values. We evaluated a PSMA PET/CT cohort of post-RP patients, focusing on patients with PSA <0.5 ng/mL. We identified a retrospective cohort who underwent piflufolastat F-18 PSMA PET/CT across an eleven-hospital system from 7/2021-2/2023. PSMA positivity was determined by radiology reports. Univariable and multivariable logistic regression identified factors associated with suspicious PSMA activity. Median PSA was 0.37 ng/mL (IQR 0.15, 1.29 ng/mL), with 49% of patients overall having at least one suspicious PSMA-avid lesion. Rates of scan positivity among patients with PSA <0.2 and 0.2-0.5 ng/mL were 34% and 38%, respectively. Among all patients, 25% (104/415) had pelvic disease (prostate bed or N1), and 24% (100/415) had M1 disease. Among patients with PSA <0.5 ng/mL, prior post-operative radiation was associated with suspicious PSMA activity. In the overall cohort, age, PSA at PSMA PET/CT, and RP Gleason Grade (GG) were associated with PSMA positivity. PSADT, EAU risk, and CAPRA-S were all associated with suspicious PSMA activity. Over one-third of patients with PSAs <0.2 ng/mL had imaging findings concerning for recurrence. Prior post-operative radiation was associated with higher rates of PSMA positivity among patients with PSA <0.5 ng/mL, and half of patients with evidence of PSMA avid distant metastatic disease underwent metastasis directed therapy. PET-PSMA imaging at low PSAs can be considered to inform salvage therapies.

Lymphatic mapping in second primary or recurrent oral cavity cancer with prior neck treatment: A case series and scoping review

ObjectivesLymphatic mapping is an established technique to map drainage patterns in oral cancer. Its utility in patients who have undergone prior radiation or neck dissection is not well studied. MethodsPatients presenting to a single tertiary cancer center between 2021–2023 for a recurrent/second oral cancer that underwent lymphatic mapping were considered. All patients had a history of a head and neck cancer treated with either radiation or neck dissection. We further conducted a scoping review in MEDLINE, Embase, and Web of Science of lymphatic mapping in oral cancer patients with previous neck treatment. ResultsIn our single center review, a total of 11 patients were included. 73 % received prior radiotherapy and 55 % underwent prior neck dissections for a head and neck cancer. Lymphoscintigraphy-directed neck dissections identified sentinel nodes in 9/11 patients, with only one patient who had positive sentinel node disease. There were no reports of regional recurrence at a median of 10 months follow-up. Our scoping review of 980 studies identified 151 additional patients who underwent sentinel node biopsy for a second oral cancer after previous neck treatment. Overall, the negative predictive value of lymphatic mapping in all studies was 96.7 %. ConclusionLymphatic mapping is feasible in secondary or recurrent oral cavity cancers even in patients with prior radiation or surgical management of the neck. The literature to date demonstrates a negative predictive value of ∼ 97 % for sentinel node mapping and warrants further consideration in the management of salvage oral cancer.

WHOLE BRAIN RADIOTHERAPY FOR INTRACRANIAL METASTATIC DISEASE IN NON-SMALL CELL LUNG CANCER: THE WESSEX EXPERIENCE

Abstract AIMS The QUARTZ trial (2016) reported that corticosteroid therapy was non-inferior to whole brain radiotherapy(WBRT) for non-small cell lung cancer (NSCLC) with regards overall survival(OS). This is a single centre experience of WBRT for NSCLC in the post-QUARTZ era and in the context of the changes in clinical practice over the past 8 years. METHOD Single centre retrospective observational study. Patients included with NSCLC treated with WBRT for radiologically confirmed intracranial (IC) metastatic disease January 2018 to December 2022. OS, baseline tumour/patient characteristics and lines of treatment were recorded from medical records. Data compiled using Excel and statistical analysis using the R language for statistical programming. RESULTS 62 patients were included, median age 64 (37 -82). 29(46.8%) were Performance status 0-1. 50(80.6%) received 20Gy in 5 fractions, 12(19.4%) received 30Gy in 10 fractions. PDL1 &amp;gt;50% in 14(22.6%), EGFR mutation positive in 10(16.1%), 0(0%) ALK/ROS mutations. 9(14.5%) had received prior radiotherapy(RT) for IC disease (SRS:8, partial brain VMAT:1). 20(32.3%) had IC disease at presentation. Median OS 68 days (95%CI:58-111;range12-777) in keeping with QUARTZ results (median OS 65 days, 95%CI:50- 78). Univariate analyses demonstrated: subsequent systemic therapy (p=0.0022), receiving immunotherapy (p=0.002) and baseline performance status (p=0.0017) associated with improved OS. PDL1 &amp;gt;50%, EGFR mutation positive, RT dose, prior systemic therapy, histological subtype, presence of a targetable mutation, first or subsequent IC treatment did not predict survival. The chi-squared test was used to compare differences in the groups with OS&amp;gt;100days(n=22) and OS&amp;lt;100days(n=40). Systemic therapy after WBRT(p=0.0011) and immunotherapy treatment(p=0.0092) were significant differences between the cohorts and associated with improved survival. CONCLUSION This data supports conclusions of QUARTZ study and it remains difficult to define a role for WBRT in the management of IC disease in NSCLC. There is a cohort who have better OS, though we believe this may be related to systemic therapy (particularly immunotherapy) exposure.

Safety of 177Lu-DOTATATE administration in a patient with recurrent meningioma complicated by radiation necrosis: a case report

Radiation-associated meningiomas are characterized by high rates of recurrence. 177Lu-DOTATATE may represent a treatment option for these tumors, but safety of this agent for patients with a history of radiation necrosis is unknown. In this case report, we describe the preliminary safety of 177Lu-DOTATATE administration for a patient with prior history of radiation necrosis. The patient was diagnosed with central nervous system (CNS) germinoma at age 17, managed with chemoradiation. Twenty years later, a left-parietal extra-axial mass was identified within the prior radiation field, with diagnosis of atypical meningioma established on subtotal resection. He received additional radiation therapy (RT, 60 Gy, 30 fractions). Seventeen months later, tumor progression was treated with gamma knife radiosurgery (GKRS, 15 Gy, single fraction). Seven months after GKRS, seizures recurred, with imaging consistent with radiation necrosis. The patient was treated with bevacizumab (7.5 mg/kg, every 3 weeks, 4 doses). One year later, magnetic resonance imaging (MRI) brain revealed tumor progression within the treatment field. 68 Ga-DOTATATE positron emission tomography demonstrated that the meningioma was DOTATATE-avid with no evidence of metastasis. The patient was treated with 177Lu-DOTATATE (two infusions, two months apart), which was well tolerated with no significant toxicities and no recurrence of radiation necrosis. Two months after the second infusion, the patient experienced disease progression and was transitioned to bevacizumab. In this patient with three prior courses of intracranial radiation and subsequent radiation necrosis, 177Lu-DOTATATE was well-tolerated. 177Lu-DOTATATE administration may be feasible for patients with a history of radiation necrosis.

Cross-Sectional Analysis of Patients Referred to a Tertiary Lymphatic Surgery Center.

Secondary lymphedema has become an increasingly common reason for referral to plastic surgery. Understanding referral patterns for lymphedema patients is crucial to optimizing care. Patients referred to plastic surgery for lymphedema at a lymphatic surgery center between January 2016 and 2023 were identified. Primary outcomes of interest included clinical lymphedema staging and characteristics, patient demographics, and referral sources. Secondary outcomes were prior lymphedema treatment, agreement between referring provider and plastic surgeon's diagnosis, and patient disposition after surgical evaluation. Descriptive statistics and multivariate logistic regression analysis were performed. A total of 285 patients with extremity edema were referred to plastic surgery; 60.0% of patients had prior malignancy, 45.6% of patients had undergone a prior lymph node procedure, and 40% had received radiation, while 56.8% of patients had previously seen occupational therapy. Body mass index (BMI, OR 1.09, p = 0.013), age (OR 1.25, p = 0.005), and prior physical oroccupational therapy (OR 1.23, p = 0.011) were associated with later stages of lymphedema upon presentation, while prior radiation (OR 0.79, p = 0.006) and malignancy (OR 0.85, p = 0.034) were associated with earlier stages of lymphedema. Self-referral (27.4%), primary care (17.9%), and medical oncology (14.7%) were the most common referral sources. Lymphedema was confirmed in 68.1% of referrals, and 28.5% of these patients proceeded to surgery. Patients were more likely to be operative candidates if referred by primary care (RR 2.1, p = 0.006) or occupational therapy (RR 4.6, p = 0.010). Referred patients ultimately undergo lymphedema surgery at relatively low rates, indicating that most referred patients are not ideal surgical candidates. Optimizing referral patterns through multidisciplinary education may enhance the referral process and improve access to lymphedema surgery.

Updated overall survival and ctDNA analysis in patients with EGFR T790M-positive advanced non-small cell lung cancer treated with lazertinib in the phase 1/2 LASER201 study.

Lazertinib is a potent, irreversible, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with significant efficacy in patients with EGFR T790M-mutated non-small cell lung cancer (NSCLC). This is the final overall survival (OS) report from the phase 1/2 LASER201 study in patients with advanced NSCLC with disease progression on or after prior EGFR TKI therapy. Eligible patients were aged ≥ 20years, with advanced EGFR-mutated NSCLC and previous therapy with EGFR TKI. Patients in this integrated analysis received oral lazertinib 240mg/day. Endpoints included efficacy and safety; exploratory analyses included associations between circulating EGFR-mutant tumor DNA (ctDNA) and efficacy parameters. This integrated analysis included 78 patients in Korea who received second- or later-line lazertinib. The median OS was 38.9months; estimated survival rates at 12, 24, and 36months were 89.5%, 73.9%, and 52.8%, respectively. The cumulative 12-month incidence of central nervous system progression was 9.4%. EGFR-mutant ctDNA was detected in 46 patients (62.2%) at baseline. The presence of ctDNA at baseline significantly predicted progression-free survival (PFS), disease control rate (DCR), and OS. PFS, response rate, and DCR were significantly associated with EGFR-mutant ctDNA clearance at cycle 3; PFS and OS were significantly associated with ctDNA clearance at cycle 5. The safety profile of lazertinib 240mg/day was consistent with previous findings. Lazertinib is a promising treatment option for patients with EGFR T790M-positive NSCLC following disease progression on prior EGFR-directed TKIs. Patients in LASER201 experienced prolonged OS, regardless of their EGFR mutation, brain metastases, or prior brain radiation status. Clearance of plasma EGFR mutations after lazertinib was associated with patient outcomes. ClinicalTrials.gov identifier NCT03046992.

12531 Long-term Safety And Efficacy Of Once-daily Oral Paltusotine In The Treatment Of Patients With Acromegaly: Update From Acrobat Advance

Abstract Disclosure: M. Gadelha: Consulting Fee; Self; Crinetics, Ipsen, Novo Nordisk, and Recordati. Grant Recipient; Self; Crinetics and Recordati. Speaker; Self; Ipsen, Novo Nordisk, and Recordati. H.S. Randeva: None. M.B. Gordon: Consulting Fee; Self; Crinetics Pharmaceuticals, HRA Pharma, Novo Nordisk, and Recordati Rare Diseases. Grant Recipient; Self; Ascendis, Camurus, Chiasma, Corcept, Crinetics, Ipsen, Novartis, Novo Nordisk, Opko, Pfizer, and Strongbridge. M. Doknic: Research Investigator; Self; Crinetics Pharmaceuticals. Speaker; Self; Merck, Novartis, Novo Nordisk, Pfizer, and Sandoz. E. Mezosi: Research Investigator; Self; Crinetics Pharmaceuticals. M. Toth: Consulting Fee; Self; Pfizer, Ipsen, Novo Nordisk, and Recordati. Research Investigator; Self; Crinetics Pharmaceuticals. Other; Self; Pfizer, Ipsen, Novo Nordisk, and Recordati. C.L. Boguszewski: Advisory Board Member; Self; Novo Nordisk and Recordati. Consulting Fee; Self; Ipsen, Novo Nordisk, and Recordati. Other; Self; Ipsen, Novo Nordisk, and Recordati. C. Davidson: Employee; Self; Crinetics Pharmaceuticals. C.T. Ferrara-Cook: Employee; Self; Crinetics Pharmaceuticals. A. Casagrande: Employee; Self; Crinetics Pharmaceuticals. A. Krasner: Employee; Self; Crinetics Pharmaceuticals. Paltusotine is a non-peptide, highly selective SST2 receptor agonist in development as a once-daily, oral treatment for patients with acromegaly or carcinoid syndrome. ACROBAT Advance is an ongoing, 6-year, single-arm, open-label extension study of paltusotine in the treatment of patients with acromegaly. Interim results as the first enrolled patients approach 4 years of treatment are reported here. Enrolled patients had completed either the ACROBAT Edge or Evolve phase 2 parent studies. In Edge, at enrollment all patients were candidates for combination drug therapy: either sub-optimally controlled on an injected SRL (octreotide or lanreotide) alone or in combination with cabergoline, or required combination therapy or pasireotide to achieve normal IGF-I levels. In Evolve, enrolled patients had normal IGF-I levels on injected SRL monotherapy. When the Advance study was initiated, paltusotine was formulated as a capsule (dose range, 10-40 mg); all patients were switched to the tablet formulation (dose range, 20-60 mg) during the third year of the study. As of this analysis, all patients had at least 2 assessments after switching to tablet formulation. Adjunctive treatment with cabergoline or pegvisomant was allowed in patients who did not attain normal IGF-I levels on the maximum dose of paltusotine. Forty-three patients were enrolled in Advance (Edge, n=32; Evolve, n=11; 88% of eligible patients): at baseline, mean (±SD) age 53.0±11.6 years, 56% female, 86% previous pituitary surgery, and none had prior radiotherapy. IGF-I control in Edge and Evolve subsets remained stable at parent study baseline values. For all patients pooled, median (IQR) IGF-I levels were 1.15× ULN (0.84, 1.46; n=43) at parent study baseline; in Advance, 1.14× ULN (0.89, 1.29; n=40), 1.06× ULN (0.87, 1.24; n=35), and 1.08× ULN (0.87, 1.57; n=10) at months 12, 24, and 42, respectively. As expected, patients receiving adjunctive medication during Advance largely derived from the Edge study. Acromegaly symptoms, as measured using the patient-reported Acromegaly Symptom Diary (score range, 0-70; higher values indicate greater symptom burden), were stably controlled: median (IQR) score of 8.6 (3.6, 20.1; n=21) at parent study baseline; in Advance, 10.5 (5.0, 18.5; n=40), 10.0 (5.0, 25.0; n=34), and 13.5 (6.0, 22.0; n=10) at months 12, 24, and 42, respectively. The most common AEs reported through month 42 were arthralgia (37.2%), headache (30.2%), and fatigue (23.3%). One serious drug-related AE (cholelithiasis) was reported. Of the 8 patients who discontinued the study, 2 were due to AEs (mild or moderate). Glycemic control, as measured by HbA1c, was stable during paltusotine treatment. In conclusion, long-term results show that once-daily oral paltusotine treatment was well tolerated, with stable biochemical and symptom control relative to that observed with injected SRLs. Support: Crinetics Pharmaceuticals. Presentation: 6/3/2024

Proton beam therapy in a patient with secondary glioblastoma (32 years after postoperative irradiation of medulloblastoma): case report and literature review

ObjectiveThis report details the experience of a patient who developed a second primary glioblastoma (GB), offering insights into the treatment process and reviewing relevant literature.Case presentationA male patient, who was diagnosed with medulloblastoma at age 9, received treatment with cobalt-60 craniospinal irradiation (CSI) (36 Gy/20 fractions) and a tumor bed boost (total of 56 Gy). After 32 years, at age 41, an MRI revealed a space-occupying mass in the left cerebellar hemisphere. Surgical resection was performed, and postoperative pathology confirmed a diagnosis of radiation-induced glioblastoma (RIGB). Given the history of irradiation and the current tolerability of brainstem doses, proton beam therapy (PBT) combined with Temozolomide (75 mg/m2) was chosen. The treatment plan included 60 Gy on the gross tumor bed and 54 Gy on the clinical target volume, delivered in 30 fractions. The patient underwent regular follow-up and achieved a complete response.Clinical discussionFor childhood cancer survivors, the development of a second primary tumor significantly impacts prognosis. RIGB is a rare form of secondary tumor with distinct molecular characteristics compared to primary GB and recurrent secondary GB. Molecular markers such as IDH and MGMT status can help differentiate between primary GB, recurrent secondary GB, and radiation-induced secondary GB in patients with a history of prior radiation therapy. Surgical resection remains a primary treatment option, while PBT is preferred for postoperative treatment due to its superior protection of normal tissues and the ability to deliver high-dose irradiation.ConclusionRIGB is a rare second primary tumor that requires strategic molecular profiling and individualized management. Proton beam therapy provides effective high-dose irradiation in the postoperative phase and is the preferred treatment option for such cases.

Secondary Pituitary Abscess: A Rare Complication of Transsphenoidal Surgery for Pituitary Adenoma - Description of Two New Cases and Review of the Literature.

Background: Pituitary abscess (PA), a rare complication following transsphenoidal (TS) surgery for pituitary adenoma with an incidence of 0.2%, poses a significant risk; carrying potential morbidity, recurrence, and the necessity for reoperation. Timely suspicion, diagnosis, and treatment are imperative. Patients and Methods: We present two cases and provide a literature review on the symptoms, risk factors, diagnosis, treatment, and outcomes associated with secondary PAs following TS surgery for adenoma. Results: We identified 12 articles reporting a total of 45 cases, in addition to our 2 cases. The primary symptoms were headache and visual impairment, with no fever or specific infectious parameters observed. Predominant risk factors identified included cerebrospinal fluid (CSF) leakage and prior radiotherapy (RT). Our first patient, a 45-year-old male, presented 10 weeks after TS surgery with sudden-onset symptoms, whereas our second patient, a 64-year-old female, presented 22 years postoperatively. In the first case, intraoperativeCSF leakage, with the patient's history of allergic rhinitis and frequent nasal irrigation possibly contributed to the development of abscess. In the second case, RT was considered a potential risk factor. Severe headache and subclinical signs of infection associated with a cystic lesion of the pituitary gland were common findings. Both patients underwent endoscopic TS drainage and received appropriate antibiotic therapy, resulting in complete recovery without recurrence. Conclusions: When faced with severe headaches in a patient with a history of TS surgery for a pituitary adenoma, coupled with radiological evidence showing a cystic appearance with peripheral enhancement, taking a proactive approach to promptly identify and intervene in secondary PAs is essential for mitigating potential complications and optimizing patient outcomes.

On the Origin of Abdominal Venous Leiomyosarcomas: The Role of the Sex-Hormone Drainage Pathways.

We hypothesized that abdominal venous leiomyosarcoma (AV-LMS) disproportionately originates in veins of the sex-hormone drainage pathway (SHDP). Our purpose was to classify the anatomical origin of AV-LMS in a large cohort using imaging and explore prognostic implications. A retrospective review of imaging of all patients presenting with abdominal non-uterine LMS at a single tertiary oncology center was performed. Inclusion criteria were a biopsy-proven LMS of non-uterine abdominal/pelvic origin with pretreatment enhanced computed tomography (CT)/magnetic resonance imaging (MRI). Patients with uterine LMS or prior radiation were excluded. LMS site of origin was assigned by one expert radiologist and indeterminate sites were reviewed with a second external expert radiologist. Locations of inferior vena cava (IVC) tumors were subclassified based on a modification of prior literature. SHDP was defined as originating from ovarian/testicular vein, distal left renal vein, adrenal vein or mid-IVC (IIA). One hundred fifty-five (155) patients were included (92/152 (61%) female) with distant metastases found at presentation in 23/155 (14.8%). Most common organs of origins were veins (84/152, 55.3%), gastrointestinal (24, 15.8%), genital (11, 7.2%) and paratesticular/spermatic cord (11, 7.2%). For venous LMS, the adrenal (both sexes), mid-IVC (IVC IIA, females) and ovarian veins had the highest relative predilection for abdominal non-uterine LMS. Eighty-four (84/152, 55.3%) of tumors were SHDP. On multivariable analysis, both size and SHDP were significant predictors of distant metastases at presentation (P = 0.01), while sex, age, organ system/site and grade were not. For both sexes, tumors arising from SHDP constitute the majority of AV-LMS and may impart a significantly lower risk of metastatic disease at presentation. Among veins, the adrenal veins had the highest predilection for LMS.

A retrospective study of prior palliative radiotherapy to the spine alongside the presence of key risk factors in the development of spinal emergencies in patients with metastatic castrate resistant prostate cancer

A retrospective study of prior palliative radiotherapy to the spine alongside the presence of key risk factors in the development of spinal emergencies in patients with metastatic castrate resistant prostate cancer

Spinal laser interstitial thermal therapy and radiotherapy for thoracic metastatic epidural spinal cord compression.

Spinal laser interstitial thermal therapy (sLITT) is a less invasive alternative to surgery for metastatic epidural spinal cord compression. Here, we analyze outcomes of patients treated with sLITT either in conjunction with radiotherapy or as a standalone salvage therapy. We included patients with thoracic vertebral metastatic cord compression treated with sLITT. Outcomes included freedom from local failure (FFLF) and overall survival (OS). Factors associated with FFLF were identified with univariable and multivariable analyses via a Cox proportional hazards model. Between 2013-2022, 129 patients received sLITT to 144 vertebral segments; 69% were radiotherapy naïve, 81% were radioresistant histologies, and 74% were centered in the vertebral body. Median age was 61 years. Pre-sLITT Bilsky score was 3 in 28%, 2 in 33%, and 1c in 37%. Radiotherapy was delivered in conjunction with sLITT for 80% of cases, including 68% that received stereotactic radiotherapy, at a median of 5 days after sLITT. Median follow-up was 9.1 months. One-year FFLF and OS was 80% and 78%, respectively. On multivariable analysis, variables independently associated with adverse FFLF included paraspinal/foraminal disease location (p = 0.001), and post-sLITT imaging Bilsky score of 2 (p = 0.073) or 3 (p = 0.011). Prior radiotherapy, technique of radiotherapy, and time between radiotherapy and sLITT were not associated with FFLF. sLITT with radiotherapy is an effective minimally invasive treatment approach for thoracic metastatic epidural spinal cord compression. Early treatment response may serve as a prognostic imaging biomarker.

Study on the Expression, Prognosis, and Clinical Features of HOXA6 in Liver Cancer

Objective: To study and analyze the expression level of homeobox A6 (HOXA6) in patients with liver cancer and its correlation with prognosis. Methods: From January 2020 to July 2021, 43 patients with liver cancer who underwent surgery without prior radiotherapy or chemotherapy were selected. Liver cancer tissues and adjacent tissues were collected, and the expression levels of HOXA6 mRNA and protein were measured using RT-qPCR and Western blot. The expression level of HOXA6 in tumor tissues (without radiotherapy and chemotherapy) was compared with that in adjacent tissues. Additionally, the prognosis and clinical characteristics of patients with low HOXA6 expression were compared to those with high HOXA6 expression, and the factors influencing high HOXA6 expression in liver cancer patients were analyzed. Results: HOXA6 mRNA and protein expression levels in tumor tissues were significantly higher than in adjacent tissues (P &lt; 0.05). There was no significant difference in the 1-year and 2-year survival rates between the high HOXA6 expression group and the low HOXA6 expression group (P &gt; 0.05). However, the 3-year survival rate was lower in the high HOXA6 expression group compared to the low HOXA6 expression group (P &lt; 0.05). There were no statistically significant differences between the two groups in terms of gender, age, tumor diameter, alpha-fetoprotein levels, or hepatitis B virus DNA levels (P &gt; 0.05). However, significant differences were found in the number of tumor lesions, degree of differentiation, and the proportion of tumor metastasis between the two groups (P &lt; 0.05). Multivariate logistic regression analysis revealed that the number of tumor lesions, degree of differentiation, and tumor metastasis were influencing factors for high HOXA6 expression in liver cancer patients (P &lt; 0.05). Conclusion: HOXA6 expression levels are abnormally elevated in liver cancer patients, and higher HOXA6 expression is associated with a worse 3-year survival rate. The factors influencing HOXA6 expression include the number of tumor lesions, degree of differentiation, and tumor metastasis.

Practice Patterns and Incidence of Febrile Neutropenia in Patients Receiving Triplet Drug Chemotherapeutic Regimens in GUT Cancers: Do We Need to Add WBC Growth Factors? (ForGeT GCSF Study)

Background and Objectives: There are limited data on the requirement and duration of white blood cell (WBC) growth factor (GF) administration in patients receiving biweekly docetaxel, oxaliplatin, leucovorin, 5 Fluorouracil (mFLOT) or modified FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, 5 Fluorouracil (mFOLFIRINOX) regimens. Methods: The data of 749 patients with pancreatic, gastric, and colorectal adenocarcinomas treated with mFOLFIRINOX or mFLOT for at least three cycles between January 2018 and December 2022 were retrieved. Results: Of the 749 patients, 387 (52%) received mFLOT, while 362 (48%) received mFOLFIRINOX. Increased use of GF was seen in patients with diabetes mellitus (70 vs. 53%; p &lt; 0.001), prior chemotherapy (82 vs. 49%; p &lt; 0.001), prior pelvic radiotherapy (89 vs. 54%; p &lt; 0.001), prior surgery (70 vs. 49%; p &lt; 0.001), and stage I to III cancers as opposed to stage IV cancers (61 vs. 48%; p = 0.006). The use of GF resulted in a statistically lesser incidence of all-grades neutropenia (2.6 vs. 18.4%; p &lt; 0.001), grade 3/4 neutropenia (1.2 vs. 12.5%; p &lt; 0.001), and the primary endpoint of febrile neutropenia (FN; 1.2 vs. 6.1%; p = 0.001). There were no differences in the incidence of all grades of neutropenia (3.7 vs. 1.9%; p = 0.527), grade 3/4 neutropenia, and the primary endpoint of FN (1.2 vs. 1.1%; p = 0.079) in patients receiving single-day versus multiday GF, respectively. Interpretation and Conclusion: The use of GF reduces the rates of FN by approximately 80% in patients receiving mFLOT and mFOLFIRINOX, although incidences of FN are low with these regimens. The incidence of febrile neutropenia was similar with single-dose versus multiday GF in efficacy when administered with mFLOT and mFOLFIRINOX chemotherapy.

ENGOT-en11/GOG-3053/KEYNOTE-B21: a randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer

Pembrolizumab plus chemotherapy provides clinically meaningful benefit as first-line therapy for advanced (locoregional extension and residual disease after surgery)/metastatic/recurrent mismatch repair-proficient (pMMR) and mismatch repair-deficient (dMMR) endometrial cancer, with greater magnitude of benefit in the dMMR phenotype. We evaluated the addition of pembrolizumab to adjuvant chemotherapy (with/without radiation therapy) among patients with newly diagnosed, high-risk endometrial cancer without any residual macroscopic disease following curative-intent surgery. We included patients with histologically confirmed high-risk [International Federation of Gynecology and Obstetrics (FIGO) stage I/II of non-endometrioid histology or endometrioid histology with p53/TP53 abnormality, or stage III/IVA of any histology] endometrial cancer following surgery with curative intent and no evidence of disease postoperatively, with no prior radiotherapy or systemic therapy. Patients were randomised to pembrolizumab 200 mg or placebo every 3 weeks (Q3W) for six cycles added to carboplatin-paclitaxel followed by pembrolizumab 400 mg or placebo every 6 weeks (Q6W) for six cycles per treatment assignment. Radiotherapy was at the investigator's discretion. The primary endpoints were investigator-assessed disease-free survival (DFS) and overall survival in the intention-to-treat population. A total of 1095 patients were randomised (pembrolizumab, n= 545; placebo, n= 550). At this interim analysis (data cut-off, 4 March 2024), 119 (22%) DFS events occurred in the pembrolizumab group and 121 (22%) occurred in the placebo group [hazard ratio 1.02, 95% confidence interval (CI) 0.79-1.32; P= 0.570]. Kaplan-Meier estimates of 2-year DFS rates were 75% and 76% in the pembrolizumab and placebo groups, respectively. The hazard ratio for DFS was 0.31 (95% CI 0.14-0.69) in the dMMR population (n= 281) and 1.20 (95% CI 0.91-1.57) in the pMMR population (n= 814). Grade ≥3 adverse events (AEs) occurred in 386 of 543 (71%) and 348 of 549 (63%) patients in the pembrolizumab and placebo groups, respectively. No treatment-related grade 5 AEs occurred. Adjuvant pembrolizumab plus chemotherapy did not improve DFS in patients with newly diagnosed, high-risk, all-comer endometrial cancer. Preplanned subgroup analyses for stratification factors suggest that pembrolizumab plus chemotherapy improved DFS in patients with dMMR tumours. Safety was manageable. ClinicalTrials.gov, NCT04634877; EudraCT, 2020-003424-17. Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Free Latissimus Dorsi Flaps in Head and Neck Reconstruction at a Modern High-Volume Microsurgery Center.

Over the past two decades, with the introduction of the perforator flap concept and advances in flap dissections, lower extremities have emerged as the preferred soft tissue flap donor sites. As a modern and high-volume microsurgical center, and the senior author being one of the pioneers and advocates for the use of lower extremity flap donor sites, we aim to investigate the role of latissimus dorsi (LD) free flap in head and neck reconstruction within our current practice. All free LD flaps used for head and neck reconstruction performed by a single surgeon between January 2010 and June 2023 were reviewed for their indications and immediate and short-term outcomes. A total of 1,586 head and neck free flap reconstructions were performed, and 33 free LD flaps were identified. The patients' median age was 53 (interquartile range [IQR] 48.5-63.5) years. Twenty-nine (87.9%) flaps were used to reconstruct oro-maxillo-facial and four (12.1%) flaps were used to reconstruct scalp defects. Most patients had prior radiation (n = 28, 84.8%), neck dissection (n = 24, 72.7%), and multiple previous head and neck flap reconstructions with a median of 3.0 (IQR 3.0-3.5) previous flaps. Six (18.2%) LD flaps were used to replace failed flaps from other donor sites. No major complications such as total flap failure or takebacks, and no need for vein grafts but three (9.1%) had flap marginal necrosis. Other complications included one flap dehiscence (3.0%), one orocutaneous fistula (3.0%), two wound infections (6.1%), three plate exposures (9.1%), and three patients who developed local recurrence (9.1%). The median patient follow-up time was 16 (IQR 5-27) months. This retrospective study demonstrates the role of LD free flap in head and neck reconstruction as a reliable and versatile backup soft tissue flap when workhorse flaps from lower extremity donor sites are either unavailable or unsuitable.

Stereotactic Radiation Therapy for Localized Prostate Cancer: 10-Year Outcomes From Three Prospective Trials

Background and purposeStereotactic ablative radiotherapy (SABR) is growingly accepted for the treatment of localized prostate cancer with recent randomized trials showing non-inferiority compared to conventional or moderately hypofractionated radiotherapy. The natural history of prostate cancer necessitates extended surveillance for recurrence; however, there are few prospective studies reporting long-term outcomes. Materials and methodsThis study included patients with low and intermediate risk localized prostate cancer from three Canadian clinical trials enrolled from 2006-2013. All patients received SABR to the prostate consisting of 35-40 Gy in 5 fractions over 11-29 days. PSA, distant metastasis, and vital status were prospectively recorded. Occurrence of second malignancy after treatment was assessed by chart review and classified using modified Cahan's criteria. Results267 patients were included. Median follow up was 10.3 years (IQR 7.8 – 12.7). 10-year BF (95% CI) was 7.7% (3.9-11.5). 10-year OS, PCSS, and FFM were 84.1% (79.3 – 89.1%), 99.2% (98.1 – 100), and 98.8% (97.5-100), respectively. 27/267 (10.1%) patients experienced a SM, with 6/27 patients (22.2%) classified as having a SM likely (n=3) or possibly (n=3) related to prior radiotherapy. 10-year freedom from SM was 89.2%. ConclusionSABR shows excellent long-term disease control for low and intermediate risk localized prostate cancer. Patients treated for prostate cancer have a moderate risk of second malignancy, consistent with background rates for the population.

Impact of Previous Surgery and/or Radiation Therapy on Endoscopic Reconstruction Outcomes.

The impact of prior local therapies, including radiation and surgery, on reconstruction outcomes after endonasal surgery is currently not well known. Reconstruction nuances in the preoperative setting merit further evaluation to avoid potential postoperative complications that can hinder overall tumor management and negatively impact patient outcome. We sought to determine whether prior treatments increase risk of reconstruction-related postoperative morbidity and to evaluate the effectiveness of our current treatment paradigm for skull base reconstruction. A retrospective review of all endonasal surgeries for tumor resection between March 2000 and March 2022 was performed. Patients were grouped based on treatment history. Patient demographics, operative, and postoperative reconstruction-related morbidity data were collected, including cerebrospinal fluid leak, sinonasal morbidity, and infectious complications. Variables significantly associated with postoperative complications in the univariate analysis were included in the multivariate Cox proportional hazards regression model. Complication-free survival curves were generated, and the log-rank test evaluated the relationship between complication-free survival and the different clinical, surgical, and treatment parameters. All statistical analyses were performed with SPSS 26 (IBM Corp) and Graph Pad 9.0 (GraphPad Software). A total of 418 patients were included. 291 patients had no prior treatments, 49 patients had previously received radiation, and 78 patients had prior surgeries. Of the 49 patients who had prior radiation, 27% underwent reconstruction with tunneled pericranial flaps vs 16% of treatment-naïve patients. On multivariate analysis, prior treatment was not significantly associated with reconstruction-related complications. Negative smoking history, no leak or small intraoperative leak, and use of vascularized flap in reconstruction were protective factors. In patients undergoing endonasal surgery, prior radiation and/or surgery does not appear to significantly increase the risk of immediate or delayed reconstruction complications using our current reconstructive management plan, which incorporates an upfront regional flap for high-risk cases.

Tyrosine-Like Crystalloids Localize to Non-Neoplastic True Vocal Cord and Attachments.

Tyrosine-rich or tyrosine-like crystalloids (TC) were initially described in salivary gland pleomorphic adenoma. The presence of TC in non-neoplastic tissues is rare, and it has been reported exclusively in the larynx. This study aims to characterize the frequency and anatomical localization of TC in total laryngectomy specimens. Review of consecutive laryngectomy specimens in which the cassette summary documented parasagittal section sampling of the right and left vocal folds and the anterior commissure. Data collected included patient demographics, underlying diagnoses, history of radiation therapy, presence, and location of TC. Of 86 laryngectomy specimens, 16 (19%) contained amphophilic to eosinophilic TC. The study cohort included 11 males and 5 females, aged 37 to 85 years (mean 62, median 63). Laryngectomy surgery was performed for advanced untreated squamous cell carcinoma (SCCa) (7/16, 43.75%), recurrent post-treatment SCCa (7/16, 43.75%), previously untreated laryngeal large cell neuroendocrine carcinoma (1/16, 6.25%), and non-functional larynx post-chemoradiation (1/16, 6.25%). According to the macroscopic cassette summary, TC were predominantly found in the anterior commissure Sect.(13/16, 81.25%), with fewer cases in sections containing the left (2/16, 12.5%) or the right (1/16, 6.25%) vocal folds. Microscopically, TC localized to the anterior macula flava and/or adjacent vocal ligament (12/16, 75%) and the anterior commissure tendon (4/16, 25%). TCs are predominantly reported as admixed with a neoplasm, however this study confirms that TC can also occur in non-neoplastic tissues of the larynx. There was no clear relationship between the presence of TC and prior radiation therapy. TC in the specialized connective tissues of the macula flava and true cord tendinous insertions distinct from tumor may form in response to alterations in mechanical stress, though an age-related change within the spectrum of normal laryngeal microanatomy also remains a possibility.

Outcomes of minimally invasive vs. open pancreatoduodenectomies in pancreatic adenocarcinoma: analysis of ACS-NSQIP data.

Pancreatoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC) presents a significant challenge owing to its aggressive nature. Traditionally performed as open surgery, the advent of minimally invasive surgery (MIS) including laparoscopic and robotic techniques, offers a potential alternative. This study assessed the use and outcomes of MIS and open PD for PDAC treatment. We analyzed ACS-NSQIP data (2015-2021) using regression models to compare patient outcomes across open PD, MIS PD, and conversions from MIS to open (MIS-O). Of 19,812 PDAC patients, 1,293 (6.53%) underwent MIS, 18,116 (91.44%) underwent open PD, and 403 (2.03%) underwent MIS converted to open PD (MIS-O). The MIS rate increased from 6.1% to 9.2%. Black patients had a higher MIS-O rate (RR, 1.55; p = 0.025). Open PD was associated with more severe conditions (ASA ≥ III, malnutrition) and prior radiation therapy. MIS patients more often had neoadjuvant chemotherapy. Complex procedures, such as vein resection, favored open PD. Need for arterial resection was associated with MIS-O (RR, 2.11; p = 0.012), and operative time was significantly associated with MIS (OR: 4.32, 95% CI: 3.43-5.43, p-value: < 0.001) No differences in the overall morbidity or 30-day mortality were observed. MIS led to shorter stays but higher risks of reoperation and pulmonary embolism. MIS-O increased the delayed gastric emptying rate (RR, 1.79; p < 0.001). During 2015-2021, an increasing number of patients with PDAC are undergoing MIS PD. Morbidity and mortality did not differ between open and MIS PD. MIS was performed more frequently in patients with better nutritional status and lower ASA, or when vascular resection was not anticipated. In well selected patients, short-term outcomes of MIS and open PD seem similar.