Concomitant Radiotherapy Research Articles

Real-Life Study of the Benefit of Concomitant Radiotherapy with Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma (cSCC): A Retrospective Cohort Study.

Cemiplimab is a monoclonal antibody targeting the PD-1, and phase II trials have shown its efficacy in the treatment of advanced cutaneous squamous cell carcinoma in patients who are not candidates for curative surgery or radiation therapy as a first- or later-line treatment. A synergistic antitumoral response has been demonstrated with concurrent radiotherapy and PD1-immunotherapy. However, no real-life study has demonstrated this effect in advanced cutaneous squamous cell carcinoma. We conducted a real-life retrospective cohort study to investigate the benefit of concomitant therapy in 33 patients treated with cemiplimab at the University Hospital of Caen, alone (C group) or concomitant to radiotherapy (C/RT group). Our primary objectives were to evaluate the best overall response and objective response rate. Our secondary objectives were the disease control rate, median time to response, progression-free survival, overall survival, clinical benefit of radiotherapy, and safety data. After stopping cemiplimab administration, we performed a follow-up of our patients and performed a descriptive study. We reported an objective response rate of 45.5%, including 47.6% in the cemiplimab group versus 41.6% in the concomitant group. The addition of radiotherapy to cemiplimab enables an earlier clinico-radiological response, with a median duration of 5.5 months in the cemiplimab group versus 3 months in the concomitant therapy group. The response to treatment was prolonged despite discontinuation of cemiplimab, with 91.6% (n = 11/12) and 83.3% (n = 10/12) patients in complete or partial remission at 6 months and 1 year after cessation of cemiplimab and no switch to another oncological treatment, respectively. Radiation therapy also provided a therapeutic effect in 83.3% of the patients in the concomitant group, without increasing the occurrence of adverse events. Our study confirms the efficacy of cemiplimab and radiotherapy in the management of advanced cutaneous squamous cell carcinoma. Concomitant therapy permitted to obtain an earlier radiological response, a beneficial local therapeutic effect of radiotherapy, without any safety alert.

Change in volumetric tumor growth rate after cytotoxic therapy is predictive of overall survival in recurrent glioblastoma.

Alterations in tumor growth rate (TGR) in recurrent glioblastoma (rGBM) after treatment may be useful for identifying therapeutic activity. The aim of this study was to assess the impact of volumetric TGR alterations on overall survival (OS) in rGBM treated with chemotherapy with or without radiation therapy (RT). Sixty-one rGBM patients treated with chemotherapy with or without concomitant radiation therapy (RT) at 1st or 2nd recurrence were retrospectively examined. Pre- and post-treatment contrast enhancing volumes were computed. Patients were considered "responders" if they reached progression-free survival at 6 months (PFS6) and showed a decrease in TGR after treatment and "non-responders" if they didn't reach PFS6 or if TGR increased. Stratification by PFS6 and based on TGR resulted in significant differences in OS both for all patients and for patients without RT (P < 0.05). A decrease of TGR (P = 0.009), smaller baseline tumor volume (P = 0.02), O6-methylguanine-DNA methyltransferase promoter methylation (P = 0.048) and fewer number of recurrences (P = 0.048) were significantly associated with longer OS after controlling for age, sex and concomitant RT. A decrease in TGR in patients with PFS6, along with smaller baseline tumor volume, were associated with a significantly longer OS in rGBM treated with chemotherapy with or without radiation. Importantly, all patients that exhibited PFS6 also showed a measurable decrease in TGR.

Presence of nodal metastasis in early oral cavity cancer: A retrospective study

Objectives: The pattern of metastasis in the neck nodes and associated clinical factors in patients with oral cavity cancer were the subjects of this research, and their patterns were evaluated.Materials and Methods: Patients with oral squamous cell carcinoma (OSCC) who did not have a history of other cancers and who were not currently undergoing neo-adjuvant concomitant chemo-radiotherapy or radiotherapy were chosen for research. In total, 300 patients met these criteria.Results: 109 out of 300 instances of oral squamous cell carcinoma patients with clinically and radio-logically N0 neck had microscopic evidence of metastatic lymphadenopathy. There is a possibility of metastases in level IIb, but they are much more common in levels IB, III, and IV. Positive nodes on level IIB were correlated with three positive nodes on level IIA. Conclusion: During the follow-up, there was a substantial correlation between the size of the primary tumor and the number of distant metastases.

Non-operable glioblastoma: Proposition of patient-specific forecasting by image-informed poromechanical model

We propose a novel image-informed glioblastoma mathematical model within a reactive multiphase poromechanical framework. Poromechanics offers to model in a coupled manner the interplay between tissue deformation and pressure-driven fluid flows, these phenomena existing simultaneously in cancer disease. The model also relies on two mechano-biological hypotheses responsible for the heterogeneity of the GBM: hypoxia signaling cascade and interaction between extra-cellular matrix and tumor cells. The model belongs to the category of patient-specific image-informed models as it is initialized, calibrated and evaluated by the means of patient imaging data. The model is calibrated with patient data after 6 cycles of concomitant radiotherapy chemotherapy and shows good agreement with treatment response 3 months after chemotherapy maintenance. Sensitivity of the solution to parameters and to boundary conditions is provided. As this work is only a first step of the inclusion of poromechanical framework in image-informed glioblastoma mathematical models, leads of improvement are provided in the conclusion.Statement of Significance: In this study, we employ mechanics of reactive porous media to effectively model the dynamic progression of a glioblastoma. Traditionally, glioblastoma tumors are surgically removed a few weeks post-diagnosis. To address this, we focus on a non-operable clinical scenario which allows us to have sufficient time points for the calibration and subsequent validation of our mathematical model. It is paramount to underscore that the tumor’s evolution is significantly influenced by chemotherapy and radiotherapy. These therapeutic effects find incorporation within our mathematical framework. Notably, the approach we present is distinctive for two key reasons: Firstly, the mathematical model inherently captures the complex multiphase and hierarchical nature of brain tissue. Secondly, our constitutive laws factor in the ever-changing properties of cells and tissues, mirroring the local phenotypic alterations observed within the tumor. This work constitutes an initial stride towards systematically integrating multiphase poromechanics into patient-specific glioblastoma growth modeling. As we look ahead, we acknowledge areas for potential enhancement in pursuit of advancing this promising direction.

Assessment of adverse drug reactions in oral cancer patients receiving chemotherapy treatment at tertiary care centres in North-Western India

Background/Aim: Pharmacovigilance in oncology is imperative as antineoplastic drugs are two-edged swords whose irrational use can pose a major health problem and a needless financial burden on the patient. The aim of this study was to study the comprehensive safety profile of anti-neoplastic drugs used for treating oral cancers. Methods: This hospital-based prospective observational study was conducted at two premiers (a government and a private) tertiary care centres in North-Western India among newly diagnosed cases of oral cancers of both sexes between the ages of 20-70 years and requiring chemotherapy treatment. The prescribing pattern of chemotherapy drugs, associated adverse effects and potential risk factors for the development of adverse effects was studied. An adverse drug reaction (ADR) causality was assessed by the WHO-UMC algorithm and preventability by Schumock and Thornton's criteria. Univariate and multivariate logistic regression analyses were used to identify the predictors related to chemotherapy-induced adverse effects. Results: The data concerned 188 patients, of which 64.3 % developed chemotherapy-related adverse effects. Among the prescribed anti-neoplastic drugs, a combination of 5-Fluorouracil, Cisplatin and Paclitaxel regimen was associated with the majority (91.42 %) of the adverse effects. Alopecia was the most common adverse effect noted in 26.44 % of patients, followed by nausea and anaemia in 15.7 % and 9.9 % of patients, respectively. Independent predictors of chemotherapy-related adverse effects were site (Adjusted odds ratio [AOR] = 1.95; 95 % CI 1.04 - 3.62, p = 0.03), chemotherapy and radiotherapy treatment (AOR = 5.00; 95 % CI 2.62 - 9.53, p &lt; 0.001), combination regimen of 5-Fluorouracil, Cisplatin and Paclitaxel (AOR = 8.68; 95 % CI 2.55 - 29.48, p = 0.001), associated comorbidities (AOR = 16.68; 95 % CI 2.45 - 28.34, p &lt; 0.001). Causality assessment revealed most adverse effects (82.64 %) to be possible. Conclusion: The adverse effect varies with the type of regimen which is prescribed for the patient. Site of cancer, concomitant radiotherapy treatment and associated comorbidities were the identifiable risk factors for developing adverse effects. Onco-pharmacovigilance studies in the future will help to provide tailored treatment to patients and improve their quality of life.

Modulation of Radiation Biomarkers in a Randomized Phase II Study of 131I-MIBG With or Without Radiation Sensitizers for Relapsed or Refractory Neuroblastoma

131I-metaiodobenzylguanidine (131I-MIBG) has demonstrated efficacy as a single agent in neuroblastoma. Recent trials have focused on 131I-MIBG combination strategies, though little is known about the effect of putative radiosensitizers on biological markers of radiation exposure. NANT2011-01 evaluated 131I-MIBG therapy alone (arm A) or in combination with vincristine/irinotecan (arm B) or vorinostat (arm C) for patients with relapsed or refractory neuroblastoma. Blood samples were collected before and after 131I-MIBG infusion to determine levels of radiation-associated biomarkers (transcript and protein). The association of biomarker with treatment arm, clinical response, and treatment toxicity was analyzed. The cohort included 99 patients who had at least 1 biomarker available for analysis. Significant modulation in most biomarkers between baseline, 72, and 96 hours following 131I-MIBG was observed. Patients in arm C had the lowest degree of modulation in FLT3 ligand protein. Lower baseline BCL2 transcript levels were associated with higher overall response. Patients with greater increases in FLT3 ligand at 96 hours after 131I-MIBG therapy were significantly more likely to have grade 4 thrombocytopenia. Peripheral blood gene expression of the BCL2 family of apoptotic markers (BCL2L1 and BAX transcripts) was significantly associated with grade 4 hematologic toxicity. RNA sequencing demonstrated little overlap in the top modulated peripheral blood transcripts between randomized arms. Peripheral blood biomarkers relevant to radiation exposure demonstrate significant modulation after 131I-MIBG and concomitant radiation sensitizers affect extent of modulation. Biomarkers related to hematopoietic damage and apoptosis were associated with hematologic toxicity.

Normofractionated irradiation and not temozolomide modulates the immunogenic and oncogenic phenotype of human glioblastoma cell lines

PurposeGlioblastoma multiforme (GBM) is the most aggressive primary brain tumor, with an overall poor prognosis after diagnosis. Conventional treatment includes resection, chemotherapy with temozolomide (TMZ), and concomitant radiotherapy (RT). The recent success of immunotherapy approaches in other tumor entities, particularly with immune checkpoint inhibitors, could not be clinically transferred to GBM treatment so far. Therefore, preclinical analyses of the expression of both immune-suppressive and immune-stimulatory checkpoint molecules following treatment of human glioblastoma cells with RT and/or temozolomide is needed to design feasible radio(chemo)immunotherapy trials for GBM in the future.MethodsFive human glioblastoma cell lines (H4, HROG-06, U118, U138, U251) were analyzed regarding their clonogenic survival and cell death forms after chemotherapy (CT) with TMZ and/or normofractionated RT (5 × 2 Gy) via multicolor flow cytometry. Further, the tumor cell surface expression of immune-activating (OX40L, CD137L, CD70, and ICOSL) and immune-suppressive (PD-L1, PD-L2, HVEM) checkpoint molecules and of an oncogenic molecule (EGFR) were measured via multicolor flow cytometry after CT and RT alone or after RCT.ResultsNormofractionated RT and not TMZ was the trigger of induction of predominantly necrosis in the glioblastoma cells. Notably, clonogenicity did not correlate with cell death induction by RT. The basal expression level of immune-suppressive PD-L1, PD-L2, and HVEM varied in the analyzed glioblastoma cells. RT, but not TMZ, resulted in a significant upregulation of PD-L1 and PD-L2 in all tumor cells investigated. Also, the expression of HVEM was increased after RT in most of the GBM cell lines. In contrast, normofractionated RT individually modulated expression of the stimulating immune checkpoint molecules CD70, CD137L, OX40L, and ICOSL1. The oncogenic factor EGFR was significantly increased by irradiation in all examined cell lines, albeit to a different extent. None of the investigated molecules were downregulated after the treatments.ConclusionNormofractionated radiotherapy modulates the immunogenic as well as the oncogenic phenotype of glioblastoma cells, partly individually. Therefore, not only PD-L1 and PD-L2, but also other immunogenic molecules expressed on the surface of glioblastoma cells could serve as targets for immune checkpoint blockade in combination with RT in the future.

48P Phase II trial on vaccination with autologous dendritic cells loaded with autologous tumour homogenate in resected glioblastoma (COMBI-GVAX): Clinical results of the first step

Glioblastoma (GBM) is a poor prognosis malignant grade IV glioma. After surgical resection, standard therapy consists of concomitant radiotherapy (RT) and temozolomide (TMZ) followed by TMZ alone. Multiple phase I/II trials and at least 3 meta-analysis showed improved survival (OS) and progression free survival (PFS) with dendritic cell (DC) vaccination in high-grade gliomas (HGGs) patients (pts). In those developing antitumor immunity, DC vaccine increases the amount of intratumoral activated cytotoxic T lymphocytes and decreases the number of FoxP3 positive regulatory T cells.

Evaluation of Adjuvant Chemotherapy Survival Outcomes Among Patients With Surgically Resected Pancreatic Carcinoma With Node-Negative Disease After Neoadjuvant Therapy

Neoadjuvant therapy (NAT) is rarely associated with a complete histopathologic response in patients with pancreatic ductal adenocarcinoma (PDAC) but results in downstaging of regional nodal disease. Such nodal downstaging after NAT may have implications for the use of additional adjuvant therapy (AT). To examine the prognostic implications of AT in patients with node-negative (N0) disease after NAT and to identify factors associated with progression-free (PFS) and overall survival (OS). A retrospective review was conducted using data from 2 high-volume, tertiary care academic centers (University of Pittsburgh Medical Center and the Medical College of Wisconsin). Prospectively maintained pancreatic cancer databases at both institutes were searched to identify patients with localized PDAC treated with preoperative therapy and subsequent surgical resection between 2010 and 2019, with N0 disease on final histopathology. Patients received NAT consisting of chemotherapy with or without concomitant neoadjuvant radiation (NART). For patients who received NART, chemotherapy regimens were gemcitabine or 5-fluoururacil based and included stereotactic body radiotherapy (SBRT) or intensity-modulated radiation therapy (IMRT) after all intended chemotherapy and approximately 4 to 5 weeks before anticipated surgery. Adjuvant therapy consisted of gemcitabine-based therapy or FOLFIRINOX; when used, adjuvant radiation was commonly administered as either SBRT or IMRT. The association of AT with PFS and OS was evaluated in the overall cohort and in different subgroups. The interaction between AT and other clinicopathologic variables was examined on Cox proportional hazards regression analysis. In this cohort study, 430 consecutive patients were treated between 2010 and 2019. Patients had a mean (SD) age of 65.2 (9.4) years, and 220 (51.2%) were women. The predominant NAT was gemcitabine based (196 patients [45.6%]), with a median duration of 2.7 cycles (IQR, 1.5-3.4). Neoadjuvant radiation was administered to 279 patients (64.9%). Pancreatoduodenectomy was performed in 310 patients (72.1%), and 160 (37.2%) required concomitant vascular resection. The median lymph node yield was 26 (IQR, 19-34); perineural invasion (PNI), lymphovascular invasion (LVI), and residual positive margins (R1) were found in 254 (59.3%), 92 (22.0%), and 87 (21.1%) patients, respectively. The restricted mean OS was 5.2 years (95% CI, 4.8-5.7). On adjusted analysis, PNI, LVI, and poorly differentiated tumors were independently associated with worse PFS and OS in N0 disease after NAT, with hazard ratios (95% CIs) of 2.04 (1.43-2.92; P < .001) and 1.68 (1.14-2.48; P = .009), 1.47 (1.08-1.98; P = .01) and 1.54 (1.10-2.14; P = .01), and 1.90 (1.18-3.07; P = .008) and 1.98 (1.20-3.26; P = .008), respectively. Although AT was associated with prolonged survival in the overall cohort, the effect was reduced in patients who received NART and strengthened in patients with PNI (AT × PNI interaction: hazard ratio, 0.55 [95% CI, 0.32-0.97]; P = .04). The findings of this cohort study suggest a survival benefit for AT in patients with N0 disease after NAT and surgical resection. This survival benefit may be most pronounced in patients with PNI.

Risk factors associated with disease recurrence in patients with T4 staged Squamous Cell Carcinoma of the Oral Cavity treated with surgery and postoperative radiotherapy.

To determine the association of clinical and pathological parameters on recurrence of treated stage T4squamous cell carcinoma of oral cavity patients managed with surgery followed by concomitant chemo and radiation therapy. The retrospective, cohort study was conducted at Patel Hospital, Karachi, and comprised data of patients diagnosed with oral squamous cell carcinoma and admitted between January 1, 2014, and January 30, 2019. Patients of either gender aged 20-80 years who had a minimum follow-up of one year were included. Data was collected using the Head and Neck Cancer registry form and the medical record files. The subjects were also contacted by telephone when needed. The study end-points were disease-free survival and overall survival. Data was analysed using SPSS 21. Out of the 83 patients, 65(78%) were male. The overall median(range) age was 46(20-80) years, and 43(52%) of them were aged 31-50 years. Overall, 15(18%) patients had positive margins and 48(58%) had proven cervical node metastasis on histopathology. Overall survival was 42.2% with the median(range) follow-up time was 14(9-21) months and 5-year disease-free survival was 45.8% with the median (range) follow-up time was 13(7-19). The factor that affected the final outcome was found to be the increasing nodal ratio (p=0.043). Among T4 oral squamous cell carcinoma patients treated with surgery and adjuvant therapy, the rate of disease recurrence was found to be high. Tumours with a high cervical nodal disease burden and/or margin involved were at substantially higher risk of recurrence.

BIOM-20. IDENTIFICATION OF BLOOD BIOMARKERS FOR DIFFERENTIATING PSEUDOPROGRESSION FROM RECURRENCE IN GLIOBLASTOMA

Abstract After the initial treatment of glioblastoma, we occasionally encounter difficulty in distinguishing between pseudoprogression and recurrence. Observation without obtaining a pathological diagnosis is a common strategy in clinical practice. If the differentiation can be achieved easily, and reliably, early treatment can be introduced appropriately, leading to the benefits of early glioblastoma treatment. In this study, we attempted to identify blood biomarkers that help distinguish between recurrence and pseudoprogression. Blood samples were collected in 25 cases of primary glioblastoma, IDH wild type, at three time points: before treatment, after standard treatment: operation and temozolomide chemotherapy with concomitant radiation therapy, and when an enhancing lesion was recognized (21 cases of recurrence, 4 cases of pseudoprogression). Gelsolin (GSN), Apolipoprotein A-IV, Osteopontin, SERPINA3, ITIH2/4 Ceruloplasmin, LRG1, Collagen-1A2, which we previously extracted as diagnostic markers, using the comprehensive proteomics SWATH method, in blood samples of healthy volunteers and patients with glioblastoma (PLoS One. 2018, J Proteome Res. 2020), were analyzed. Absolute quantitative values of candidate molecules in the blood were obtained using a commercially available enzyme-linked immunoassay. Among the candidate molecules, GSN was significantly lower in pseudoprogression than in recurrence (p = 0.0032), and ROC analysis showed sensitivity of 95%, specificity of 100%, and an AUC = 0.98, which makes GSN a useful molecule to consider as a differential marker. We previously reported that GSN, actin binding protein, and inflammation markers are downregulated in glioblastoma (Cancer Sci. 2020). In summary, GSN was extracted as a candidate blood biomarker for the diagnosis of pseudoprogression. We are planning to validate the research with nationwide multi-institutional studies.

RTID-05. TRIAL IN PROGRESS: DOSE-FINDING STUDY AND EVALUATION OF [177LU]LU-DOTA-TATE IN COMBINATION WITH STANDARD OF CARE IN NEWLY DIAGNOSED GLIOBLASTOMA AND AS A SINGLE AGENT IN RECURRENT GLIOBLASTOMA

Abstract Patients with glioblastoma have a poor prognosis despite extensive efforts to develop new treatments. Standard of care for newly diagnosed patients is surgery followed by radiotherapy plus temozolomide. However, temozolomide only provides a clinical benefit to patients who have glioblastomas with a methylated O(6)-methylguanine-DNA methyltransferase (MGMT) gene promotor. Disease recurrence is inevitable and subsequent treatments have poor outcomes due to limited efficacy and a lack of established therapeutic regimens. [68Ga]Ga-DOTA-TATE is a radioligand imaging agent that selectively binds to somatostatin receptors (SSTRs) and is used with positron emission tomography (PET) for the molecular imaging of SSTR-positive neuroendocrine tumors. Glioblastoma tumoral PET scans have shown moderate uptake of [68Ga]Ga-DOTA-TATE. The radioligand therapy [177Lu]Lu-DOTA-TATE has the same SSTR-targeted ligand and demonstrated promising clinical activity in a pilot study in patients with Grade III/IV gliomas. This Phase 1b open-label dose-finding study (NCT05109728) will determine the recommended [177Lu]Lu-DOTA-TATE dose in three different groups of glioblastoma (newly diagnosed with methylated MGMT promoter [group 1], newly diagnosed with unmethylated MGMT promoter [group 2], and recurrent disease [group 3]). All participants will be scanned with [68Ga]Ga-DOTA-TATE imaging during screening and, for each group, approximately 15 participants will be enrolled in consecutive cohorts of 3–6 participants. All participants will receive up to 6 administrations of [177Lu]Lu-DOTA-TATE (initial dose 150 mCi with 3 provisional dose levels up to 250 mCi) using the Bayesian Optimal Interval design. Group 1 will receive [177Lu]Lu-DOTA-TATE every 4 weeks with concomitant radiotherapy and temozolomide, followed by temozolomide maintenance. Group 2 will receive [177Lu]Lu-DOTA-TATE every 4 weeks for 3 doses with radiotherapy then every 3 weeks as a single agent. Group 3 will receive [177Lu]Lu-DOTA-TATE only, every 3 weeks. The primary endpoint is incidence of dose limiting toxicity. Secondary endpoints include overall objective status (modified RANO criteria), progression free survival, overall survival and safety.

CTNI-21. TROTABRESIB (CC-90010) IN COMBINATION WITH CONCOMITANT TEMOZOLOMIDE PLUS RADIOTHERAPY AND ADJUVANT TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA: UPDATED RESULTS FROM A PHASE 1B/2 STUDY

Abstract Trotabresib, a novel bromodomain and extraterminal protein inhibitor, has demonstrated antitumor activity and blood–brain barrier penetration in patients with high-grade gliomas, and enhanced the antiproliferative effects of temozolomide in preclinical models. CC-90010-GBM-002 (NCT04324840) is a phase 1b/2 study investigating the addition of trotabresib to standard-of-care (SOC) concomitant temozolomide plus radiotherapy and adjuvant temozolomide, followed by maintenance trotabresib, in patients with newly diagnosed glioblastoma. The design of the dose escalation (part A) has been described previously (Vieito M, et al. SNO 2021. Abstract CTNI-51). Primary objectives of part A were to establish the safety, tolerability, and maximum tolerated dose/recommended phase 2 dose (RP2D) of trotabresib. In part A, addition of trotabresib to SOC was safe and well tolerated in the concomitant (N = 14) and adjuvant (N = 18) cohorts; the most frequent grade 3/4 treatment-related adverse event was thrombocytopenia (7/14 and 9/18 patients, respectively). The RP2D for trotabresib was 30 mg/day 4 days on/24 days off in both settings. At data cutoff (February 20, 2022), median duration of treatment was 34 weeks (concomitant cohort) and 33 weeks (adjuvant cohort); progression-free survival data are not yet mature. Trotabresib plasma pharmacokinetics and pharmacodynamics were consistent with monotherapy. At last follow-up, 6 and 5 patients remained on treatment in the concomitant and adjuvant dose-escalation cohorts, respectively, including 1 patient in cycle 20 with ongoing complete response. The ongoing randomized phase 2 dose expansion (part B; planned N = 162) is comparing concomitant trotabresib at the RP2D + SOC followed by adjuvant trotabresib at the RP2D + SOC, followed by maintenance trotabresib 45 mg/day 4 days on/24 days off, versus SOC alone in patients with newly diagnosed IDH–wild-type glioblastoma. Key objectives are to compare progression-free and overall survival, safety, and tolerability. Longer follow-up from part A and the first disclosure of data from part B will be presented.

194P A study of the treatment response of concomitant external beam radiotherapy (EBRT) and intracavitary brachytherapy in the management of locally advanced carcinoma of uterine cervix

194P A study of the treatment response of concomitant external beam radiotherapy (EBRT) and intracavitary brachytherapy in the management of locally advanced carcinoma of uterine cervix

Safety of CDK4/6 inhibitors and concomitant radiation therapy in patients affected by metastatic breast cancer

PurposeCyclin-dependent kinase 4/6 inhibitors (CDK4/6i) currently represent the standard of care for the initial treatment of patients with metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. The aim of our study is to evaluate the safety of the use of concomitant radiation therapy (RT) in a consecutive series of HR+/HER2- patients treated in two academic institutions with CDK4/6i in the metastatic setting. Methods and materialsFrom September 2017 to February 2020, we retrospectively collected and analysed data on a sequential series of patients treated with CDK4/6i, receiving RT or not, at two European institutions. Primary outcome of the study was the association between RT and any adverse events (AEs) ≥ G3. Secondary outcomes were the association between RT and any AEs (any grade), CDK4/6i dose reduction rate, and CDK4/6i treatment discontinuation rate. ResultsWe analysed a total of 132 consecutive women; RT was prescribed in 57 (43.2%) patients (70 irradiated lesions). The median age of the series was 52.1 years (range 32.3–78.2). Concomitant RT administration was not significantly related to higher AEs ≥ G3 (p = 0.19) and any grade AEs (p = 1.0); there was no association with RT and CDK4/6i dose reduction (p = 0.49) and discontinuation rates (p = 0.14). At a median follow-up of 18.8 months, the progression-free survival (PFS) rate was 35% and the overall survival (OS) rate was 38.7% in the whole group. The use of concomitant RT did not affect both PFS (p = 0.71) and OS rates (p = 0.55). ConclusionsOur data are encouraging regarding the safety of this combination, showing that concurrent RT did not increase severe toxicity and did not have an impact on systemic treatment conduction.

The Incidence Rate of Radiation Pneumonitis Observed in Patients Treated with Thoracic Radiotherapy and Concurrent First-Generation EGFR-TKIs, Second-Generation EGFR-TKIs or Third-Generation EGFR-TKIs in Advanced Lung Adenocarcinoma

<h3>Purpose/Objective(s)</h3> The main aim of this study was to evaluate the incidence rate of radiation pneumonitis (RP) in advanced lung adenocarcinoma treated with first-generation, second-generation, or third-generation EGFR-TKIs combined with thoracic radiotherapy. <h3>Materials/Methods</h3> We retrospectively evaluated advanced lung adenocarcinoma patients simultaneously treated with first-generation EGFR-TKIs, second-generation, or third-generation EGFR-TKIs and thoracic radiotherapy between January 2015 to December 2021 at Shandong Cancer Hospital and Institute. The clinical grades of RP were evaluated according to the pneumonitis of Common Toxicity Criteria (CTC) 5.0 Grading System, and the imaging grading of RP was evaluated using the pulmonary fibrosis of CTC 5.0 Grading System. <h3>Results</h3> Consecutive 100 patients who were treated with first-generation EGFR-TKIs were enrolled, 20 patients were treated with second-generation EGFR-TKIs and 50 patients who received third-generation EGFR-TKIs (10:2:5 matched with patients and tumor characteristics), and all three groups were concurrent with thoracic radiotherapy. In terms of overall incidence of RP, first-generation group versus second-generation group versus third-generation group of clinical grades were 2.083 vs 2.389 vs 1.935, and their imaging grades were 1.753 vs 1.895 vs 1.524. The incidence of the imaging grading of grade greater than or equal to 3 RP in three groups were 22% vs 15% vs 4%, and the clinical grades of grade greater than or equal to 3 RP in three groups were 28% vs 55% vs 20%. Other details can be referred to in the Table. <h3>Conclusion</h3> Patients treated with third-generation EGFR-TKIs combined with thoracic radiotherapy achieved minimum probability of RP. In contrast, the second-generation EGFR-TKIs concomitant thoracic radiotherapy are the most likely to happen RP. The clinical grades and imaging grades were not completely same in RP.

Factors on development and severity of acute radiodermatitis: prospective single-center study

Aim: Although prior literature has examined the treatment and patient-associated factors affecting the development and severity of acute radiodermatitis, there are relatively few prospective studies evaluating both. This study was prospectively designed to evaluate factors affecting the development and extent of radiation-induced acute skin toxicity called radiodermatitis (RD). &#x0D; Material and Method: A total of 63 patients who underwent radiotherapy (RT) in Ankara Atatürk Research and Education Hospital between July 2017 and October 2018 were evaluated. Patients’ demographic status, disease/treatment details, hemoglobin, ferritin, folic acid, Vit B12, and hemoglobin A1c values were recorded. The development and grade of RD were evaluated weekly by the same radiation oncologist using the Radiation Therapy Oncology Group (RTOG) radiation toxicity guideline.&#x0D; Results: There was no significant relationship between the development of any degree of RD and gender, concomitant chemotherapy (CT), pre-RT CT, comorbid disease, RT technique and blood parameters (Hb, Hba1c, ferritin, folic acid and B12). The development of grade 2-3 RD was significantly affected by the number of operations (p=0.032) and total dose of RT (p=0.008). In patients with grade 2/3 RD, the RT dose at which RD first appeared was 20 Gy (range, 14-36); in patients with grade 1 RD, this value was 32 Gy (range, 16-56) (p=0.018).&#x0D; Conclusion: There is no significant relationship between the development of acute radiodermatitis and Hba1c, hemoglobin, ferritin, B12 and folic acid levels. There was a significant correlation between grade of RD and repeated surgery, increase in total RT dose and early onset of RD.

Diagnostic Performance of Whole-Body Ultra-Low-Dose CT for Detection of Mechanical Ventriculoperitoneal Shunt Complications: A Retrospective Analysis.

Radiographic shunt series are still the imaging technique of choice for radiologic evaluation of VP-shunt complications. Radiographic shunt series are associated with high radiation exposure and have a low diagnostic performance. Our aim was to investigate the diagnostic performance of whole-body ultra-low-dose CT for detecting mechanical ventriculoperitoneal shunt complications. This retrospective study included 186 patients (mean age, 54.8 years) who underwent whole-body ultra-low-dose CT (100 kV[peak]; reference, 10 mAs). Two radiologists reviewed the images for the presence of ventriculoperitoneal shunt complications, image quality, and diagnostic confidence. On a 5-point Likert scale, readers scored image quality and diagnostic confidence (1 = very low, 5 = very high). Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Radiation dose estimation of whole-body ultra-low-dose CT was calculated and compared with the radiation dose of a radiographic shunt series. 34 patients positive for VP-shunt complications were correctly identified on whole-body ultra-low-dose CT by both readers. No false-positive or -negative cases were recorded by any of the readers, yielding a sensitivity of 100% (95% CI, 87.3%-100%), a specificity of 100% (95% CI, 96.9%-100%), and perfect agreement (κ = 1). Positive and negative predictive values were high at 100%. Shunt-specific image quality and diagnostic confidence were very high (median score, 5; range, 5-5). Interobserver agreement was substantial for image quality (κ = 0.73) and diagnostic confidence (κ = 0.78). The mean radiation dose of whole-body ultra-low-dose CT was significantly lower than the radiation dose of a conventional radiographic shunt series (0.67 [SD, 0.4] mSv versus 1.57 [SD, 0.6] mSv; 95% CI, 0.79-1.0 mSv; P < .001). Whole-body ultra-low-dose CT allows detection of ventriculoperitoneal shunt complications with excellent diagnostic accuracy and diagnostic confidence. With concomitant radiation dose reduction on contemporary CT scanners, whole-body ultra-low-dose CT should be considered an alternative to the radiographic shunt series.

S3419 Ileocolitis Associated With the Checkpoint Inhibitor Palbociclib (PAL)

Introduction: Cancer treatments are continuously being updated to optimize survival. Newer checkpoint inhibitors (CDK4/6 inhibitors) have demonstrated promising responses in ER-positive breast cancers. We report a rare side effect of ileocolitis with Palbociclib (PAL) treatment. Case Description/Methods: A 30-year-old female with biopsy confirmed stage IV ER+, PR+, HER2− ductal breast carcinoma with metastasis to liver and bone presented with abdominal pain, diarrhea, and hematochezia 2 months into therapy with letrozole and PAL. Subsequent colonoscopy 4 months after onset of symptoms showed diffuse colitis with congestion, erythema, and shallow ulceration scattered through the whole colon, and several superficial aphthous ulcerations in the ileum. Stool for C. difficile by PCR was negative and biopsies revealed nonspecific ileitis and colitis. There was concern for IBD vs drug induced enteritis/colitis. PAL was held and the patient was started on prednisone taper with resolution of symptoms after 1 month. Given concern for disease progression, PAL was restarted 1 month later with return of symptoms and hospital admission. Laboratory studies showed WBC 1.84 TH/uL, Hgb 7.6 g/dL, plt 24 TH/uL, LDH 4211 U/L, ALT 450 U/L, AST 221 U/L, alk phos 223 U/L, total bilirubin 1.3 mg/dL, ESR 49 mm/hr and CRP 45 mg/L. Infection was excluded via stool studies including C. difficile PCR and blood culture. Colonoscopy was performed and showed erythema, friability, congestion, erosions, and ulceration in the TI compatible with ileitis (Figure) as well as patchy erythema, edema, erosions, and ulcers throughout the colon with skip lesions and sparing of the rectum. Biopsies were reported as normal TI and colon. PAL was discontinued indefinitely and the patient had complete resolution of symptoms within weeks. Discussion: CDK4/6 inhibitors are new first-line treatment for metastatic HR-positive breast cancer. There are no prior reports of PAL induced enterocolitis without concomitant radiation. In our patient, symptoms could not be easily distinguished from infectious colitis or IBD clinically. Ileal and colonic biopsies showed nonspecific ileitis and colitis or were reported as normal. As CDK4/6 inhibitors become used more as the first-line treatment of metastatic HR-positive breast cancer, additional evidence of GI related toxicities may emerge. Checkpoint inhibitor induced ileitis/colitis should be considered in a patient with new onset hematochezia and diarrhea after initiation of these agents.Figure 1.: Erythema, friability, congestion, erosions, and ulceration in the terminal ileum.

397. NEOADJUVANT CHEMORADIOTHERAPY VERSUS NEOADJUVANT CHEMOTHERAPY AND POSTOPERATIVE COMPLICATIONS AFTER ESOPHAGECTOMY FOR CANCER

Abstract Postoperative complications after esophagectomy are common. Neoadjuvant chemotherapy or chemoradiotherapy in addition to surgery is the standard treatment with curative intent for patients with locally advanced esophageal cancer. The aims of our study were to analyze if the addition of neoadjuvant radiotherapy to chemotherapy and surgery increases the rate and severity of postoperative complications and to evaluate if radiotherapy doses to the heart and lungs were associated with postoperative complications. The study was based on a prospectively collected database of esophageal cancer patients that were operated on between October 2008 and March 2020. Patients treated with neoadjuvant chemoradiotherapy were compared to patients treated with neoadjuvant chemotherapy. All postoperative complications were graded according to the Clavien Dindo classification. The primary outcome was 30-day postoperative complications. Logistic regression was used to determine the effect of radiotherapy on complication rates. Several dose/volume parameters for the lungs and the heart were considered. During the study period esophagectomy was performed on 275 patients after neoadjuvant treatment (93 after chemotherapy and 182 after chemoradiotherapy). The median total radiation dose was 41.4 Gy, the median lung dose was 6.2 Gy and the median dose to the heart was 20.3 Gy. Neoadjuvant chemoradiotherapy compared to chemotherapy showed no association with postoperative complications of a Clavien Dindo score of ≥2 or severe postoperative complications (Clavien Dindo ≥3b). Taxane-containing chemotherapy had a statistically significant association with postoperative complications (table 1). The radiotherapy dose to the heart and lungs had no significant association with postoperative complications. In our cohort, the addition of preoperative radiotherapy to chemotherapy did not increase the rate of postoperative complications. However, an association between postoperative complications and taxane-containing chemotherapy regimens given with or without concomitant radiotherapy was noted.