Course Of Chemoradiotherapy Research Articles

The experience of using chemoradiotherapy for esophageal cancer with the FOLFOX chemotherapy regimen

Introduction. For an extended period, numerous studies have been conducted to find the optimal treatment regimen for esophageal cancer. Chemoradiotherapy has demonstrated satisfactory results in the treatment of localized and locally advanced forms of this disease. However, the search for the best chemotherapy regimen in combination with radiotherapy remains a current focus of many researchers.Aim. To evaluate the effectiveness and safety of chemoradiotherapy (CRT) using the FOLFOX regimen in patients with esophageal cancer.Materials and methods. A prospective study was conducted at the Ulyanovsk Regional Clinical Oncology Dispensary. The analysis included patients who received chemoradiotherapy with the FOLFOX regimen from December 1, 2022, to March 1, 2024. A total of 19 cases of esophageal cancer treatment at stages I–III were analyzed. Radical surgical treatment was subsequently performed on 5 patients (26.3%). The characteristics of the studied patients were evaluated according to a standardized protocol.Results. In the study group, 18 patients (94.7%) completed the planned course of treatment. One patient received an incomplete course of radiotherapy but completed the entire planned chemotherapy. The most common hematologic complication was leukopenia, observed in 9 patients (47.3%) after the full course of chemoradiotherapy. No cases of febrile neutropenia were reported. The hematologic complications were manageable and did not lead to the discontinuation of treatment. Among non-hematologic complications, the most frequently reported were grade 1–2 nausea in 11 patients (58%) and grade 1–2 vomiting in only 2 cases (10%), which was effectively controlled with antiemetic therapy. Overall and relapse-free survival were assessed. The reason for discontinuing radiotherapy in 1 patient (5.3%) was ulcerative stomatitis. Surgery was performed on 5 patients, with tumor regression (TRG) grades 1–2 according to the Mandard scale observed in 4 of them (80%). One patient (20%) had a TRG 3 response.Conclusions. After chemoradiotherapy with the FOLFOX regime in patients with squamous cell carcinoma of the esophagus, the rate of therapeutic tumor regression (TRG1–2) in operated patients reached 80%. One-year relapse-free survival was 58%, one-year overall survival was 73%, indicating the effectiveness and safety of this chemotherapy regimen as part of the comprehensive treatment of esophageal cancer.

Dynamics of cell-free tumor DNA correlate with early MRI response during chemoradiotherapy in rectal cancer

BackgroundIn locally advanced rectal cancer, the prediction of tumor response during and after neoadjuvant treatment remains challenging. In terms of organ preservation, adaptive radiotherapy, and intensified (total) neoadjuvant therapies, biomarkers are desirable for patient stratification.MethodsIn 16 patients, weekly blood samples (n = 86) to detect cell-free tumor DNA (ctDNA) during long-course neoadjuvant chemoradiotherapy were analyzed. Data were correlated with initial tumor volumes, MRI response in week 2 and 5 of radiotherapy as well as with pathologic tumor response after resection and outcome parameters.ResultsMost patients showed decreasing ctDNA during the course of radiochemotherapy. However, we found heterogenous dynamics of ctDNA and could identify three groups: (1) decline (2) no clear decline and/or late shedding (3) persistence of ctDNA. In seven patients we could detect significant amounts of ctDNA in week 5 or week 6 of treatment. In our pilot cohort, we did not find significant correlations of ctDNA dynamics with pathologic response or outcome parameters. However, patients with distinct decline of ctDNA had larger tumor volumes prior to treatment, and MRI imaging in week 2 and 5 revealed bigger absolute decrease of tumor volumes. If significant levels of ctDNA were found in week 5 and / or 6, patients showed less absolute tumor volume decrease in week 2 and 5.ConclusionsWeekly measurement of ctDNA during radiochemotherapy is feasible and might represent a promising biomarker. Bigger initial primary tumors showed different ctDNA shedding profiles compared with smaller primary tumors and correlations of ctDNA dynamics with early imaging response were found.

Nutritional support for cancer patients during chemoradiation treatment

An analysis of publications in the medical databases e-Library, PubMed, and Medline (2005–2024) was conducted to evaluate the impact of nutritional support on the tolerability of antitumor chemoradiotherapy. Based on the data collected, it was revealed that chemoradiotherapy is linked to a high risk of developing protein-energy malnutrition. Consequently, the initial nutritional deficiency and sarcopenia result in either a refusal to administer chemotherapy in favor of radiation treatment alone, a forced reduction in the dose of a cytostatic medication, or the disruption of the chemoradiotherapy course. Patients with malignancies of the head and neck who have received chemoradiotherapy with previous induction chemotherapy are in the “red zone” for the risk of developing protein-energy malnutrition. Nutritional support is one of the instruments that enhances the likelihood of treatment implementation and mitigates the risk of drug and radiation toxicity. The fundamental principles of nutritional support during chemoradiotherapy include timely prescription, adequacy, composition of a specialized mixture, and the choice of the most physiological way of its implementation. Supplementing nutritional support with feasible strength physical exercise triggers protein synthesis in skeletal muscles, increases muscular sensitivity to the anabolic properties of amino acids, and mitigates insulin resistance.

Programmed cell death 1 inhibitor sintilimab plus concurrent chemoradiotherapy for locally advanced pancreatic adenocarcinoma.

Pancreatic adenocarcinoma, a malignancy that arises in the cells of the pancreas, is a devastating disease with unclear etiology and often poor prognosis. Locally advanced pancreatic cancer, a stage where the tumor has grown significantly but has not yet spread to distant organs, presents unique challenges in treatment. This article aims to discuss the current strategies, challenges, and future directions in the management of locally advanced pancreatic adenocarcinoma (LAPC). To investigate the feasibility and efficacy of programmed cell death 1 (PD-1) inhibitor sintilimab plus concurrent chemoradiotherapy for LAPC. Eligible patients had LAPC, an Eastern cooperative oncology group performance status of 0 or 1, adequate organ and marrow functions, and no prior anticancer therapy. In the observation group, participants received intravenous sintilimab 200 mg once every 3 wk, and received concurrent chemoradiotherapy (concurrent conventional fractionated radiotherapy with doses planning target volume 50.4 Gy and gross tumor volume 60 Gy in 28 fractions and oral S-1 40 mg/m2 twice daily on days 1-14 of a 21-d cycle and intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-d cycle for eight cycles until disease progression, death, or unacceptable toxicity). In the control group, participants only received concurrent chemoradiotherapy. From April 2020 to November 2021, 64 participants were finally enrolled with 34 in the observation group and 30 in the control group. Thirty-four patients completed the scheduled course of chemoradiotherapy, while 32 (94.1%) received sintilimab plus concurrent chemoradiotherapy with 2 patients discontinuing sintilimab in the observation group. Thirty patients completed the scheduled course of chemoradiotherapy in the control group. Based on the Response Evaluation Criteria in Solid Tumors guidelines, the analysis of the observation group revealed that a partial response was observed in 11 patients (32.4%), stable disease was evident in 19 patients (55.9%), and 4 patients (11.8%) experienced progressive disease; a partial response was observed in 6 (20.0%) patients, stable disease in 18 (60%), and progressive disease in 6 (20%) in the control group. The major toxic effects were leukopenia and nausea. The incidence of severe adverse events (AEs) (grade 3 or 4) was 26.5% (9/34) in the observation group and 23.3% (7/30) in the control group. There were no treatment-related deaths. The observation group demonstrated a significantly longer median overall survival (22.1 mo compared to 15.8 mo) (P < 0.05) and progression-free survival (12.2 mo vs 10.1 mo) (P < 0.05) in comparison to the control group. The occurrence of severe AEs did not exhibit a statistically significant difference between the observation group and the control group (P > 0.05). Sintilimab plus concurrent chemoradiotherapy was effective and safe for LAPC patients, and warrants further investigation.

Psychosocial consequences of head and neck cancer symptom burden after chemoradiation: a mixed-method study.

Patients with head and neck cancer (HNC) experience significant symptom burden from combination chemotherapy and radiation (chemoradiation) that affects acute and long-term health-related quality of life (HRQOL). However, psychosocial impacts of HNC symptom burden are not well understood. This study examined psychosocial consequences of treatment-related symptom burden from the perspectives of survivors of HNC and HNC healthcare providers. This was a cross-sectional, mixed-method study conducted at an NCI-designated comprehensive cancer center. Participants (N = 33) were survivors of HNC who completed a full course of chemoradiation (n = 20) and HNC healthcare providers (n = 13). Participants completed electronic surveys and semi-structured interviews. Survivors were M = 61years old (SD = 9) and predominantly male (75%), White (90%), non-Hispanic (100%), and diagnosed with oropharynx cancer (70%). Providers were mostly female (62%), White (46%) or Asian (31%), and non-Hispanic (85%) and included physicians, registered nurses, an advanced practice nurse practitioner, a registered dietician, and a speech-language pathologist. Three qualitative themes emerged: (1) shock, shame, and self-consciousness, (2) diminished relationship satisfaction, and (3) lack of confidence at work. A subset of survivors (20%) reported clinically low social wellbeing, and more than one-third of survivors (35%) reported clinically significant fatigue, depression, anxiety, and cognitive dysfunction. Survivors of HNC and HNC providers described how treatment-related symptom burden impacts psychosocial identity processes related to body image, patient-caregiver relationships, and professional work. Results can inform the development of supportive interventions to assist survivors and caregivers with navigating the psychosocial challenges of HNC treatment and survivorship.

Circulating tumor cells reveal early predictors of disease progression in patients with stage III NSCLC undergoing chemoradiation and immunotherapy

Circulating tumor cells (CTCs) are early signs of metastasis and can be used to monitor disease progression well before radiological detection by imaging. Using an ultrasensitive graphene oxide microfluidic chip nanotechnology built with graphene oxide sheets, we were able to demonstrate that CTCs can be specifically isolated and molecularly characterized to predict future progression in patients with stage III non-small cell lungcancer (NSCLC). We analyzed CTCs from 26 patients at six time points throughout the treatment course of chemoradiation followed by immune checkpoint inhibitor immunotherapy. We observed that CTCs decreased significantly during treatment, where a larger decrease in CTCs predicted a significantly longer progression-free survival time. Durvalumab-treated patients who have future progression were observed to have sustained higher programmed death ligand 1+ CTCs compared to stable patients. Gene expression profiling revealed phenotypically aggressive CTCs during chemoradiation. By using emerging innovative bioengineering approaches, we successfully show that CTCs are potential biomarkers to monitor and predict patient outcomes in patients with stage III NSCLC.

Assessment of the quality of life in complex medical rehabilitation of patients at the stage of chemoradiotherapy for head and neck cancer

BACKGROUND: At the stage of chemoradiotherapy of malignant neoplasms of the head and neck, in 90% of cases, the development of radiation dermatitis and mucositis is observed. The resulting acute radiation reactions negatively affect not only the quality of life of the patient, but also the planned treatment. A multidisciplinary approach with the inclusion of basic treatment, physical therapy, physical factors, psychological correction, and nutritional support is an effective strategy for improving the patient's quality of life at this stage of treatment. AIM: To assess the quality of life of patients in complex medical rehabilitation who underwent chemoradiotherapy for malignant neoplasms of the head and neck. MATERIALS AND METHODS: An interventional prospective randomized study was conducted with the participation of 60 patients with malignant neoplasms of the oral cavity, larynx, oropharynx, larynx undergoing chemoradiotherapy. The main group (n=30) received a course of medical rehabilitation: exposure to low-temperature argon plasma, general magnetic therapy, physical therapy, training on the support reaction on a barefoot platform, nutritional support and classes with a medical psychologist. In patients of the comparison group (n=30), plasma exposure was not included in the rehabilitation course. The effect of chemoradiotherapy for head and neck cancer on the patient's quality of life was assessed by the severity of pain syndrome, physical functioning, and limitations of daily activities using Visual Analogue Scale (VAS), Hospital Anxiety and Depression Scale (HADS) techniques, a questionnaire developed by C.D. Spielberger and adapted by Y.L. Khanin, the SF-36 questionnaire. RESULTS: After a course of chemoradiotherapy, patients began to complain of pain, burning in the mouth, complaints of dry mouth, pain when swallowing, eating, limited mouth opening, redness and peeling of the skin, voice changes, difficulty falling asleep, frequent awakenings at night, embarrassment of one’s appearance. In patients of both groups, there was a decrease in the level of reactive and personal anxiety, the increased level of anxiety and depression decreased by the end of the course of chemoradiotherapy with a decrease in indicators after 6 months. Despite the increase in pain intensity during chemoradiation treatment, an increase in vital activity indicator was recorded, as well as an indicator of self-assessment of one’s health by the end of the course of chemoradiation treatment. CONCLUSION: The resulting radiation mucositis and epidermitis at the stage of chemoradiotherapy for head and neck cancer lead to physical and psychological limitations, worsening the patient's quality of life, which determines the need to accompany this stage of treatment with comprehensive medical rehabilitation. The study of the dynamics of the parameters of the quality of life of patients is the basis for the selection of individual rehabilitation treatment programs.

Clinical experience of combined organ-preserving treatment of laryngopharyngeal cancer with spread to the cervical esophagus

Introduction. Laryngopharyngeal cancer accounts for about half of the total number of malignant neoplasms of ENT organs. Despite the availability of examination, in most patients tumors of this localization are detected at late stages, and the long-term results of treatment of locally advanced cancer of the larynx remain unsatisfactory.Clinical case. This article presents two clinical cases of combined organ-preserving treatment of laryngopharyngeal cancer with spread to the cervical esophagus. At the first stage, patients underwent organ-preserving surgical treatment with a reconstructive plastic component according to the methodology developed at the A.F. Tsyb Medical Radiological Research Center – branch of the National Medical Research Center of Radiology. Then a postoperative course of chemoradiotherapy was carried out.Conclusion. The use of combined organ-preserving techniques using displaced skin-muscle flaps in the treatment of locally advanced laryngopharyngeal cancer involving the cervical esophagus allows in some cases to avoid crippling surgery, preserve the larynx and achieve satisfactory functional results, which significantly improves the quality of life of patients.

Treatment of Central Nervous System Tumors on Combination MR-Linear Accelerators: Review of Current Practice and Future Directions.

Magnetic resonance imaging (MRI) provides excellent visualization of central nervous system (CNS) tumors due to its superior soft tissue contrast. Magnetic resonance-guided radiotherapy (MRgRT) has historically been limited to use in the initial treatment planning stage due to cost and feasibility. MRI-guided linear accelerators (MRLs) allow clinicians to visualize tumors and organs at risk (OARs) directly before and during treatment, a process known as online MRgRT. This novel system permits adaptive treatment planning based on anatomical changes to ensure accurate dose delivery to the tumor while minimizing unnecessary toxicity to healthy tissue. These advancements are critical to treatment adaptation in the brain and spinal cord, where both preliminary MRI and daily CT guidance have typically had limited benefit. In this narrative review, we investigate the application of online MRgRT in the treatment of various CNS malignancies and any relevant ongoing clinical trials. Imaging of glioblastoma patients has shown significant changes in the gross tumor volume over a standard course of chemoradiotherapy. The use of adaptive online MRgRT in these patients demonstrated reduced target volumes with cavity shrinkage and a resulting reduction in radiation dose to uninvolved tissue. Dosimetric feasibility studies have shown MRL-guided stereotactic radiotherapy (SRT) for intracranial and spine tumors to have potential dosimetric advantages and reduced morbidity compared with conventional linear accelerators. Similarly, dosimetric feasibility studies have shown promise in hippocampal avoidance whole brain radiotherapy (HA-WBRT). Next, we explore the potential of MRL-based multiparametric MRI (mpMRI) and genomically informed radiotherapy to treat CNS disease with cutting-edge precision. Lastly, we explore the challenges of treating CNS malignancies and special limitations MRL systems face.

Predictors of Tumor Dynamics during a 6-Week Course of Chemoradiotherapy for Glioblastoma

Our prior imaging studies have shown geometrically meaningful inter-fraction tumor dynamics specific to glioblastoma (GBM). We aim to identify predictors associated with tumor dynamics during a 6-week course of concurrent chemoradiotherapy (CRT) for GBM. Patients enrolled in a prospective serial magnetic resonance imaging (MRI) study were reviewed. All patients were treated with 54-60 Gy in 30 fractions. The gross tumor volume (GTV) included the surgical cavity and T1c enhanced residual tumor; clinical tumor volume (CTV) included GTV with a 15mm isotropic expansion, respecting anatomical boundaries; planning target volume (PTV) was 4mm expansion. MRIs were obtained at RT planning (F0), fraction 10 (F10), and fraction 20 (F20). Tumor dynamic metrics (relative to F0) assessed included the GTV volume (Vrel), Hausdorff distance (dH) and migration distance (dM). dH is the average distance between two datasets in metric space. dM is the maximum linear displacement of the GTV in any direction. Factors to be determined associated with tumor dynamics included: age, sex, corpus callosum (CC) involvement, extent of surgery (gross total resection (GTR), subtotal resection (STR) or biopsy alone (Bx)), MGMT methylation and IDH mutation status. A total of 129 patients were reviewed. Median GTV was 20.9cc at F0, 17.6cc at F10 (Vrel 0.85), and 16.1cc at F20 (Vrel 0.78). Patients without CC involvement had more marked GTV volume reduction: Vrel 0.82 vs 1.02 with CC involvement at F10 (P = 0.05), and Vrel 0.77 vs 0.88 with CC involvement at F20 (P = 0.03). Patients with GTR (vs STR vs Bx) had more marked GTV volume reduction across all time points: Vrel 0.78, 0.85 and 1.07 respectively at F10 (P = 0.001), and Vrel 0.69, 0.80, 1.04 respectively at F20 (P = 0.001). The median dH was 8.1mm at F10 and 9.2mm at F20. Patients with CC involvement (vs without CC involvement) had a larger dH: 54% vs 25% had dH>10mm respectively at F10 (P = 0.03), and 73% vs 28% had dH>10mm respectively at F20 (P<0.005). Patients with a GTR had smaller dH at both F10 (P = 0.02) and F20 (P = 0.006). At F20, 20%, 47% and 37% of patients with GTR, STR and Bx had dH>10mm (P = 0.04). The median dM were 4.7mm at F10 and 4.7mm at F20. Patients with CC involvement (vs without CC involvement) had larger dM: 41% vs 12% had dM >10mm respectively at F10 (P = 0.01), and 45% vs 9% had dM >10mm respectively at F20 (P<0.001). Patients with GTR had smaller dM at F10 (P = 0.03) and F20 (P0.002). At F20, 0%, 25% and 19% of patients with GTR, STR and Bx had dM>10mm (P = 0.002). Age, sex, MGMT methylation and IDH mutation status were not associated with Vrel, dH and dM at F10 and F20. We identified CC involvement and extent of surgery to be associated with tumor dynamics at F10 and F20 over the course of CRT for GBM. This offers opportunities to better select patients who may benefit from earlier/ more frequent RT replan/ adaptation to ensure adequate tumor coverage, or to reduce RT toxicities.

Spectroscopic MRI Detects Occult Glioblastoma Invasion during Chemoradiation

The standard of care for glioblastoma (GBM) includes surgical resection followed by adjuvant chemoradiation (chemoRT). Treatment margins are controversial since conventional imaging does not define the extent of infiltrating tumor cells. Whole-brain spectroscopic MRI (sMRI) allows for visualization of native metabolites in normal brain and tumor cells, and the relative choline to N-acetyl-aspartate ratio greater than 2 (rChoNAA>2) strongly correlates with the presence of occult GBM cells in otherwise normal-appearing brain. With an MRI-Linac, we are performing studies of adaptive radiotherapy to measure changes in cavity size, edema, and enhancement during chemoRT. We questioned whether rChoNAA>2 would change along with anatomical changes to inform clinical target volumes for adaptive chemoRT trials. In a prospective study, 18 patients with primary GBM underwent daily MRI-guided chemoRT with standalone 3T sMRI generation of rChoNAA>2 maps at three timepoints before, during, and after chemoradiation. Conventional treatment volumes of T1 post-contrast and cavity (GTV2, i.e., boost) with or without FLAIR hyperintensity (GTV1) were compared to rChoNAA>2 volumes. DICE similarity coefficients were calculated to assess the spatial similarity of these volumes. Hausdorff distances were calculated to identify rChoNAA>2 extending beyond GTVs throughout the course of chemoradiation. The mean GTV1 was 58.1 cc (range 0-251.4 cc), the mean GTV2 was 47.9 cc (range 0-139.9 cc), and the mean rChoNAA>2 volume was 31.1 cc (range 0-103.2 cc). rChoNAA>2 volumes did not significantly change over the course of chemoRT or correlate with measurement timepoint. The mean DICE similarity coefficient between GTV1 and rChoNAA>2 volumes was 0.39 (range 0-0.80), and the mean DICE similarity coefficient between GTV2 and rChoNAA>2 volumes was 0.29 (range 0-0.77). DICE similarity coefficients were significantly different from unity indicating spatial differences between rChoNAA>2 and conventional MRI volumes. The mean Hausdorff distances of rChoNAA>2 extending beyond GTV1 was 1.3 cm (range 0.7-2.1 cm), and the mean Hausdorff distances of rChoNAA>2 extending beyond GTV2 was 1.9 cm (range 0.8-2.9 cm), suggesting high-risk disease invading beyond what is visible on conventional MRI sequences. Whole-brain sMRI with generation of rChoNAA>2 maps suggest conventional MRI does not fully capture the extent of disease in primary GBM throughout the course of chemoradiation. rChoNAA>2 maps often extend up to approximately 2 cm beyond conventional boost radiotherapy volumes. Further studies are ongoing to determine how sMRI can be used to adapt radiation target volumes during chemoradiation and escalate dose to occult disease.

Outcomes of Moderately Dose Escalated Hypofractionated Chemoradiation for Pancreatic Cancer

A modestly hypofractionated course of chemoradiation (CRT) consisting of 36 Gy/15 fractions (F) concurrent with gemcitabine used in PREOPANC and phase II trials has become increasingly common for the treatment of borderline resectable (BR) and locally advanced (LA) pancreatic cancer (PC). Achieving an R0 resection remains a key prognostic factor in PC. We tested whether escalating dose beyond standard dosing (SD) of 36-39 Gy/15 F (or 50-54 Gy/25-30 F) would improve R0 resection rates and outcomes while respecting nearby organs at risk. This was a retrospective analysis of consecutive patients at our institution from 2012-2022 with BR/LA PC treated with moderate dose escalated (MDE) (45 Gy/15 F, N = 45) or SD (36-39 Gy/15 F, N = 68 or 50-54 Gy/25-30 F, N = 25) CRT. For MDE, a 5 mm expansion from the duodenum, small bowel, and stomach was created (GI_PRV); PTV was cropped from this structure and prescribed 45 Gy/15 F. The primary endpoint was R0 resection rate with secondary endpoints of cumulative incidence of local progression (LP, recurrence after surgery/imaging progression if no surgery) with death as a competing risk (LP after occurrence of distant metastasis [DM] were still captured), cumulative incidence of DM, and overall survival (OS). Univariable and multivariable competing risks regression analyses were performed to determine the association between baseline covariates and LP. We identified 45 patients treated with MDE and 93 treated with SD. Most patients presented with BR disease (55.6% MDE; 54.8% SD) and received neoadjuvant chemotherapy with FOLFIRINOX (98% MDE; 99% SD). All patients in the MDE group and 99% in the SD group received concurrent chemotherapy with gemcitabine used most often (96% MDE; 77% SD). Median follow-up was 17 m (IQR 13-27 m). Surgical resection rates were similar between groups (33.3% MDE vs. 39.8% SD, p = 0.46). Amongst patients that had surgery, R0 resection rates were non-significantly higher in the MDE group (73.3% vs. 47.4%, p = 0.09). Cumulative incidence of LP at 18 m was significantly lower in the MDE group (9.0% vs. 24.8%, p = 0.04). No difference in rates of DM (51.2% MDE vs. 59.6% SD, p = 0.92) or OS at 18 m (53.9% vs. 53.6%, p = 0.89) were observed. On multivariable analysis, MDE (HR = 0.39, p = 0.03) and pancreatic head location (HR = 0.51, p = 0.04) were the only factors independently associated with LP. Rates of grade 2+ gastrointestinal toxicity during CRT (20% MDE vs. 20.9% SD, p = 0.91) and ≤90 days of completing CRT (11.6% MDE vs. 14.8%, p = 0.62) were similar between groups, as were rates of grade 3+ hematologic toxicity (52.3% MDE vs. 41.3% SD, p = 0.23). In this single institutional study, we found MDE is a simple, safe, and effective strategy associated with improved local control, higher R0 resection rates, and similar toxicity to SD CRT for patients with BR/LA PC. Further prospective data is needed to clarify the role of dose-escalated RT in the management of this lethal malignancy.

L-Glutamine and Survival of Patients with Locally Advanced Head and Neck Cancer Receiving Chemoradiotherapy.

We previously reported that L-glutamine reduces the severity of mucositis caused by chemoradiotherapy in patients with head and neck cancer. However, the impact of glutamine on the anti-tumor effect of chemoradiotherapy remains controversial. This study, which included 40 patients, investigated whether L-glutamine influences survival. Radiation therapy (total: 66 or 70 Gy), cisplatin, and docetaxel were co-administered for a period of 6 weeks. Patients were randomly assigned to receive either glutamine (glutamine group, n = 20) or placebo (placebo group, n = 20) during the entire course of chemoradiotherapy. We compared the overall survival and progression-free survival rates between the two groups. At 5-year follow-up, 16 (80%) and 13 (72%) patients in the glutamine and placebo groups, respectively, survived (with no significant difference in overall survival [glutamine group: 55.2 ± 12.7 months vs. placebo group: 48.3 ± 21.3 months]). A total of 14 (70%) and 12 (67%) patients in the glutamine and placebo groups, respectively, did not experience disease progression (with no significant difference in progression-free survival [glutamine group: 46.7 ± 19.5 months vs. placebo group: 43.6 ± 25.2 months]). These findings indicate that L-glutamine does not influence the survival of patients with locally advanced head and neck cancer receiving chemoradiotherapy.

Minimally invasive treatment of multiple primary tumors of the gastrointestinal tract. Clinical observation

For now days we don’t have any guidelines for the treatment of synchronous and metachronous tumors of the upper and lower gastrointestinal tract. In this case report, we are talking about optimal treatment strategy in a patient with early gastric cancer, a neuroendocrine tumor of the sigmoid colon, and a locally advanced rectal cancer. The patient underwent laparoscopic gastrectomy and endoscopic excision of the early neuroendocrine tumor of the sigmoid colon. View of the local advanced rectal cancer patient underwent combined preoperative “sandwich” treatment with 2 courses of chemotherapy before a long course of chemoradiotherapy and 2 courses of chemotherapy after. The treatment was well tolerated. Ten weeks later, the patient gets surgical procedure: laparoscopic low anterior resection with loop colostomy followed by adjuvant chemotherapy. At the end of chemotherapy colostomy closure was done. The minimally invasive surgical treatment is safe and feasible in patients with synchronous malignancies of upper and lower gastrointestinal tract. Fast track rehabilitation and minimal surgical trauma ensure timely delivery of chemotherapy.

115 Predictors of Tumour Dynamics During a Six-Week Course of Chemoradiotherapy for Glioblastoma

115 Predictors of Tumour Dynamics During a Six-Week Course of Chemoradiotherapy for Glioblastoma

The HI-FIVE Trial: A Prospective Trial Using 4-Dimensional 68Ga Ventilation-Perfusion Positron Emission Tomography-Computed Tomography for Functional Lung Avoidance in Locally Advanced Non-small Cell Lung Cancer

Functional lung avoidance (FLA) radiation therapy aims to spare regions of functional lung to reduce toxicity. We report the results of the first prospective trial of FLA using 4-dimensional gallium 68 ventilation-perfusion positron emission tomography-computed tomography (68Ga-4D-V/Q PET/CT). Inclusion criteria required a diagnosis of stage III non-small cell lung cancer and the ability to undergo radical-intent chemoradiation therapy. Functional volumes were generated using planning 68Ga-4D-V/Q PET/CT. These volumes were used to generate a clinical FLA plan to 60 Gy in 30 fractions. The primary tumor was boosted to 69 Gy. A comparison anatomic plan was generated for each patient. Feasibility was met if FLA plans (compared with anatomic plans) allowed (1) a reduction in functional mean lung dose of ≥2% and a reduction in the functional lung volume receiving 20 Gy (fV20Gy) of ≥4%, and (2) a mean heart dose ≤30 Gy and relative heart volume receiving 50 Gy of <25%. In total, 19 patients were recruited; 1 withdrew consent. Eighteen patients underwent chemoradiation with FLA. Of the 18 patients, 15 met criteria for feasibility. All patients completed the entire course of chemoradiation therapy. Using FLA resulted in an average reduction of the functional mean lung dose of 12.4% (SD, ±12.8%) and a mean relative reduction of the fV20Gy of 22.9% (SD, ±11.9%). At 12 months, Kaplan-Meier estimates for overall survival were 83% (95% CI, 56%-94%) and estimates for progression-free survival were 50% (95% CI, 26%-70%). Quality-of-life scores were stable across all time points. Using 68Ga-4D-V/Q PET/CT to image and avoid functional lung is feasible.

Abstract 2375: Whole exome sequencing and immune profiling of cervical adenocarcinoma reveal a “cold” tumor-immune phenotype

Abstract Purpose: Cervical adenocarcinomas (CAC), a less common cervical cancer histology with poor prognosis as compared to squamous cell carcinoma (CSCC), disproportionally present at advanced stages in young women and incidence is increasing; however, the same chemoradiation (CRT) paradigm is used by clinicians for both histologies. Given the rarity of CAC, little is known about genomic pathways and tumoral immune factors that differentiate CAC from CSCC and could drive differences in patient outcomes. Objective: To identify distinctions in the mutational landscape and immune phenotype of CAC and CSCC tumors in patients undergoing CRT which may be potential therapeutic targets. Methods: 80 patients with FIGO stage IB-IVA cervical cancer who underwent definitive CRT were prospectively enrolled on an IRB approved clinical trial. Cervical tumor DNA (9 CAC patients; 58 CSCC patients) and cervical tumor microenvironment samples (13 CAC patients, 67 CSCC patients) were collected by a noninvasive swab technique at baseline, and after 1, 3, and 5 weeks of CRT. WES and neoantigen prediction were performed and tumor mutation burden (TMB) was calculated as the number of somatic coding mutations per megabase. Lymphocyte immunostaining was performed according to standard protocols and cells were analyzed using a LSRFortessa X-20 Flow Cytometer (BD Biosciences) and FlowJo 10.6.1. Statistical comparison of mean values was performed by t-test. Results: Baseline mean TMB and tumor neoantigen was lower in CAC compared to CSCC (1.1±0.14 vs 5.2±3.5 respectively for TMB, p&amp;lt;0.01; 6.0±8.5 vs 455.3±472.5 respectively for neoantigen, p&amp;lt;0.01) and persisted during CRT. The top 3 most frequently altered genes unique to CAC were GPR98, SLC12A3, and TP53. The baseline mutational profile of CAC tumors was most similar to other adenocarcinomas including prostate and pancreatic cancer in TCGA. There was a significant reduction for CAC in baseline CD4+ T-cell infiltration in CAC compared to CSCC (p=0.01) which persisted through the course of CRT (p=0.02 at week 3). There was a trend toward decreased CD4+ T-cell activation, including co-expressing CD69 (p=0.17) and Ki67 (p=0.06), decreased CD8+ T-cell infiltration (p=0.19), and decreased Ki67+CD8+ T-cells as compared to CSCC (p=0.02). Conclusions: In contrast to CSCC, immune profiling of the CAC tumor microenvironment suggests a reduction in immune cell infiltrate and absence of or failed T-cell activation. Similarly, unique genetic alterations were detected between histologies, and CAC tumors displayed reduced TMB and loss of tumor neoantigen expression. These findings are consistent with an “immune cold” phenotype in CAC. These patients may be less likely to benefit from immunotherapy. Future investigation into molecularly targeted therapies or strategies that help mobilize peritumoral T-cells in response to CRT may better potentiate improved CRT response in CAC. Citation Format: Julianna Bronk, Xiaogang Wu, Rui Wang, Ananta Yanamandra, Tatiana Karpinets, Chike Abana, Molly El Alam, Katarina Tomasic, Daniel Lin, Erica Lynn, David Lo, Timothy Harris, Xingzhi Song, Andrew Futreal, Jianhua Zhang, Jagannadha Sastry, Ann Klopp, Lauren Colbert. Whole exome sequencing and immune profiling of cervical adenocarcinoma reveal a “cold” tumor-immune phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2375.

Results of multicomponent treatment of patients with progression of primary brain glioma

The aim of this study was to determine the most effective approach to the treatment of patients with continuous growth of brain glioma.Material and Methods. The study included 200 patients with progression of primary brain glioma, who were treated at the Chelyabinsk Regional Center of Oncology and Nuclear Medicine in the period from 2001 to 2021. The average age of patients was 47.86 ± 11.47 years. The ratio of men to women was 1:1. The continuous growth of high-grade glioma was detected in 125 cases. The progression of lowgrade glioma was observed in 40 patients. Transformation of low-grade glioma into high-grade glioma was found in 35 patients. Re-surgery was performed in 92 patients. Repeated radiation therapy was given to 140 patients. Chemotherapy as the method of choice was administered to 60 patients.Results. The median overall survival (OS) time was 36 months. The 1and 2-year survival rates were 96.0 % and 59.4 %, respectively. The method-specific overall survival time was 15 months. There was a tendency towards an increase in OS in all subgroups of patients who underwent re-surgery. The highest method-specific overall survival rates were observed in patients who received stereotactic radiation therapy (STRT) and combined photon-neutron therapy (CPNT): 23 and 47 months in patients with high-grade glioma and 60 and 72 months in patients with continuous growth of low-grade glioma, respectively (p&gt;0.05). In patients with the transformation of low-grade glioma into high-grade glioma, the method-specific OS was higher in patients who received combination of chemotherapy and radiation therapy compared to those who received chemotherapy or radiation therapy alone: 32, 12, and 24 months, respectively (p&gt;0.05).Conclusion. Repeated surgery is the optimal treatment approach for patients with continuous growth of primary brain glioma. In cases with repeated radiotherapy courses, CPNT or STRT can be the methods of choice. Treatment of patients with transformation of low-grade gliomas into high-grade gliomas should include repeated course of chemoradiotherapy.

Photodynamic therapy treatment of oral cavity cancer in patients with comorbidities

We report the experience of radical treatment by photodynamic therapy of patients with squamous cell carcinoma of oral cavity with serious side diseases. Completed treatment of two patients with serious side diseases (HIV infection with associated pulmonary hypertension of high degree and cardiac pathology) suffered from cancer of oral cavity. Extensive surgical treatment and/or aggressive course of chemoradiation therapy were not indicated to them due to concomitant pathology. Both patients were diagnosed with squamous cell carcinoma of oral cavity, with appropriate stage Ist. сT1N0M0. Patients received treatment by photodynamic therapy with chorine photosensitizer in dose 1 mg/kg. Options of photodynamic were: output power – 1.5W, power density – 0.31 W/cm2, light dose – 300 J/cm2. After one time session of photodynamic therapy, in both cases full response was diagnosed (according to RECIST 1.1). In one case the second session of photodynamic therapy was performed due to concomitant disease of oral cavity – multiply lesions of leukoplakia and after was diagnosed full remission of all lesions. Major adverse event was pain during the first 5-7 days after treatment, curable by painkillers. Follow-up (IQR) was 12 and 18 month respectively with no evidence of progression. It is available to avoid extensive surgical treatment and aggressive course of chemoradiation therapy (as an alternative) with the use of photodynamic therapy. Photodynamic therapy is minimally invasive method of radical treatment of localized squamous cell carcinoma of oral cavity with minimal adverse events, and could be especially relevant in patients with serious concomitant diseases.

Abstract P021: Association of social determinants of health and healthcare-related factors with delayed total neoadjuvant therapy among rectal cancer patients from the national cancer database

Abstract Total neoadjuvant therapy (TNT) is a treatment strategy for rectal cancer that includes a course of chemotherapy and a separate course of chemoradiation before definitive surgery. The use of TNT has increased in recent years and carries the potential for improved sphincter preservation and a significant risk reduction of locoregional recurrence. One criterion of the National Accreditation Program for Rectal Cancer is to begin definitive treatment within 60 days of a patient’s diagnosis of rectal cancer. The objective of this study was to evaluate the association of social determinants of health and healthcare-related factors with starting TNT 60 days or more after diagnosis using data from the National Cancer Database (NCDB). Patients aged 18 years and older diagnosed with primary rectal cancer between 2016 and 2019, who underwent NCCN recommended TNT regimen followed by definitive surgery at a Commission on Cancer (CoC)-accredited facility and did not die before receiving surgery were eligible for the current study. We included 3,210 patients in the analytic sample who did not have the following conditions: clinical stage IV, clinical stage T1N0 or lower, non-adenocarcinoma histology, and adjuvant therapy use. Logistic regression models were used to estimate the odds ratio (OR) and 95% confidence intervals (CI) for factors potentially associated with starting TNT more than 60 days after a cancer diagnosis. The median age of patients included in the study was 57 years old, with a majority of them starting TNT within 60 days (87.5%), were males (62.3%), and reported as Non-Hispanic White race and ethnicity (76.7%). Furthermore, 35.0% had a median household income of $63,333 or more, 57.7% had private insurance/managed care, 65.0% traveled within 30 miles to their treatment facility, and 49.1% lived in a zip code where less than 10.9% of adults age 25 or older did not graduate from high school. In multivariable models, factors positively associated with starting TNT after 60 days or more were uninsured status (OR 2.93, CI: 1.84, 4.67), living in a zip code with more than 10.8% of adults age 25 or older not graduating from high school (OR 1.66, CI: 1.22, 2.25), traveling more than 30 miles to the treatment facility (OR 1.63, CI: 1.20, 2.20), treatment with an academic/research program (OR 1.51, CI: 1.13, 2.02), Medicaid as primary insurance (OR 1.50, CI: 1.03, 2.19), Hispanic ethnicity (OR 1.44, CI: 1.00, 2.07), male (OR 1.28, CI: 1.00, 1.65) and age (1.02, CI: 1.01, 1.04). In conclusion, results from this study show that social determinants of health and other healthcare-related factors are significantly associated with those who started TNT more than 60 days after a rectal cancer diagnosis. Further investigation is ongoing to understand the impact of delays in TNT and other treatment regimens for rectal cancer. Citation Format: Megan T. Mai, Zheng Shi, Duke Appiah. Association of social determinants of health and healthcare-related factors with delayed total neoadjuvant therapy among rectal cancer patients from the national cancer database. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P021.