Conventional Chemoradiotherapy Research Articles

Efficacy and safety analysis of TACE + sunitinib vs. sunitinib in the treatment of unresectable advanced renal cell carcinoma: a retrospective study

BackgroundSince renal cell carcinoma(RCC) is insensitive to conventional chemoradiotherapy, molecularly targeted drugs are commonly used treatments for unresectable advanced RCC. The aim of this study was to explore the efficacy and safety of TACE + sunitinib vs. sunitinib in the treatment of unresectable advanced RCC. MethodsThis study included 98 patients with unresectable advanced RCC who were treated in Union Hospital from January 2015 to December 2018, and they met the criteria. They were divided into two groups: TACE + Sunitinib group (N = 47) and Sunitinib group (N = 51). We conducted a retrospective study to analyze the efficacy and safety of the two groups of patients.Results(1)TACE + Sunitinib group: 4 patients (8.5%) achieved CR, 27 patients (57.5%) achieved PR, 9 patients (19.1%) achieved SD, and 7 patients (14.9%) achieved PD. Sunitinib group, 0 patients (0%) achieved CR, 20 patients (39.2%) achieved PR, 14 patients (27.5%) achieved SD, and 17 patients (33.3%) achieved PD. (P = 0.017) (2)ORR: TACE + sunitinib group, 66.0%; sunitinib group, 39.2%. (P = 0.009) (3)DCR: TACE + sunitinib group, 85.1%; sunitinib group, 66.7%. (P = 0.038) (4) In the TACE + sunitinib group, mPFS was 15.6 months, mOS was 35.0 months; in the sunitinib group, the mPFS was 10.9 months, mOS was 25.7 months. (P < 0.001) (5) The incidence of abdominal pain, fever, and vomiting was higher in the TACE + sunitinib group than in the sunitinib group (abdominal pain: 55.3% vs. 13.7%; fever: 61.7% vs. 7.8%; vomiting: 40.4% vs. 19.6%; P < 0.05). The technical success rate of TACE in TACE + Sunitinib group is 100%.ConclusionsThe TACE + sunitinib group had higher ORR and DCR, longer OS and PFS than the sunitinib alone group. TACE combined with sunitinib can play a complementary role and is a safe and effective treatment for advanced RCC.

Abstract P4-01-06: LP-184, an acylfulvene class small molecule therapeutic, is synthetically lethal in HR deficient and PARP inhibitor resistant triple negative breast cancer

Abstract Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer accounting for approximately 15% to 20% of all newly diagnosed breast cancer cases. TNBCs are defined by lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2).Due to its special molecular phenotype, it is not sensitive to endocrine therapy or targeted therapy. Therefore, chemotherapy such as anthracyclines or taxanes is the main systemic treatment, but the efficacy of conventional postoperative adjuvant chemoradiotherapy is poor. ~35% of TNBC tumors show abnormalities in the HR pathway, making them sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) and DNA-damaging agents. Although more than 40% BRCA1/2-deficient patients fail to respond to PARPi and a substantial proportion of patients acquire PARPi resistance over time. TNBCs heterogeneous nature, poor prognosis and limited treatment options presents the urgent need of development of novel agents targeting tumor specific alterations. Lantern Pharma is advancing LP-184, an acylfulvene-derived prodrug that is specifically activated in tumors that overexpress the oxidoreductase enzyme Prostaglandin Reductase 1 (PTGR1), for the treatment of solid tumor indications including TNBC. LP-184 has multiple mechanisms of action (MOA). While It is synthetically lethal in tumors harboring DNA damage repair defects including Homologous Recombination (HR) deficiencies, it can also interrupt transcription. LP-184 efficacy was tested in a panel of breast cancer cell lines and patient derived TNBC xenografts models, both sensitive as well as resistant to PARP inhibitors and anthracyclines. LP-184 demonstrated nanomolar potency in six NCI-60 breast cancer cell lines (median IC50 = 327 nM). Subcutaneous patient-derived TNBC xenograft mouse models were used to determine tumor volume responses to LP-184 treatment in vivo. Xenograft tumors were derived from 10 treatment-naive HR deficient (HRD score &amp;gt; 50) primary TNBC patients with known BRCA1/2 loss of heterozygosity (LOH), 7 of which subsequently progressed on PARP inhibitor Olaparib. LP-184 (4mg/kg i.v., (q2d x 5 then 7 days off)x2) led to complete and durable regression in all 10 TNBC HRD-PDX models tested as compared to control (p &amp;lt; 0.0001). A tumor growth inhibition range of 107-141% was achieved across all the 10 models. For LP-184, T/C at the control group end day was 0% in 10/10 models, whereas across the same models for Olaparib, T/C was 0% in 2/10 models and ranged from 15 - 90% in 8/10 models. Terminal body weight change was only a transient weight loss &amp;lt; 4% with LP-184 treatment across all models. LP-184 exhibited superior potency than olaparib in TNBC PDX models that carry HRD mutations including PARP resistant models and was well tolerated in mice. As acylfulvene-induced damage is primarily repaired by transcription-coupled nucleotide-excision repair (TC-NER) and HR pathways, response to LP-184 is influenced by tumor DNA damage repair pathway status. Recent data highlight an important role of super enhancer driven core transcription regulatory circuits in the pathogenesis of TNBCs. Our results support the superior efficacy of LP-184 in TNBCs, likely linked to the multiple MOAs, and establish LP-184 as a promising new agent for future clinical testing in TNBC patients. We finally propose that LP-184 may be broadly efficacious in solid tumors with HR and/or TC-NER pathway defects, such as pancreatic, prostate, ovarian and bladder cancers. Citation Format: Aditya Kulkarni, Neha Biyani, Laura Brullé-Soumaré, Stefano Cairo, Panna Sharma, Kishor Bhatia. LP-184, an acylfulvene class small molecule therapeutic, is synthetically lethal in HR deficient and PARP inhibitor resistant triple negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-06.

Whole view of the immune microenvironment of biliary tract cancer

Biliary tract cancer is a group of malignancies which originate from biliary epithelium, and adenocarcinoma is the main pathological type. Although surgical resection is the only radical treatment strategy, most biliary tract cancer patients are diagnosed at locally advanced stage or with distant metastasis. Biliary tract cancer is highly resistant to the conventional chemoradiotherapy and the emerging immunotherapy including immune checkpoint inhibitors, owing to the suppressive immune microenvironment. In a whole view, this paper discussed the anti-tumor and tumor-promoting immune responses of the various immune cells and stromal cells in the immune microenvironment of biliary tract cancer, as well as their correlation with prognosis. The understanding of the whole view of immune microenvironment in biliary tract cancer patients could further inform the design of clinical trials of immunotherapy or combination therapy.

Downsizing of rectal cancer following neoadjuvant radiotherapy (5 × 5 Gy) and long interval surgery evaluated using MRI semiautomated volumetric measurements, a retrospective study.

Neoadjuvant conventional chemoradiation (CRT) is the standard treatment for primary locally non-curatively resectable rectal cancer, as tumor downsizing may allow R0 resectability. Short-term neoadjuvant radiotherapy (5x5 Gy) followed by an interval before surgery (SRT- delay) is an alternative for multimorbid patients who cannot tolerate CRT. This study examined the extent of tumor downsizing achieved with the SRT-delay approach in a limited cohort that underwent complete re-staging before surgery. Between March 2018 and July 2021, 26 patients with locally advanced primary adenocarcinoma (>uT3 or/and N+) of the rectum were treated with SRT-delay. 22 patients underwent initial staging and complete re-staging (CT, endoscopy, MRI). Tumor downsizing was assessed by staging and re-staging data and pathologic findings. Semiautomated measurement of tumor volume was performed using mint Lesion™ 1.8 software to evaluate tumor regression. The mean tumor diameter determined on sagittal T2 MRI images decreased significantly from 54.1 (23-78) mm at initial staging to 37.9 (18-65) mm at re-staging before surgery (p <0.001) and to 25.5 (7-58) mm at pathologic examination (p <0.001). This corresponds to a mean reduction in tumor diameter of 28.9 (4.3-60.7) % at re-staging and 51.1 (8.7-86.5) % at pathology. Mean tumor volume determined from transverse T2 MR images mint LesionTM 1.8 software significantly decreased from 27.5 (9.8 - 89.6) cm3 at initial staging to 13.1 (3.7 - 32.8) cm3 at re-staging (p <0.001), corresponding to a mean reduction of 50.8 (21.6 - 77) %. The frequency of positive circumferential resection margin (CRM) (less than 1mm) decreased from 45,5 % (10 patients) at initial staging to 18,2 % (4 patients) at re-staging. On pathologic examination, the CRM was negative in all cases. However, multivisceral resection for T4 tumors was required in 2 patients (9%). Tumor downstaging was noted in 15 of 22 patients after SRT-delay. In conclusion, the observed extent of downsizing is broadly comparable to the results of CRT, making SRT-delay a serious alternative for patients who cannot tolerate chemotherapy.

Implications of recent neoadjuvant clinical trials on the future practice of radiotherapy in locally advanced rectal cancer.

Over the last two decades, the standard treatment for locally advanced rectal cancer (LARC) has been neoadjuvant chemoradiotherapy plus total mesorectal excision followed by adjuvant chemotherapy. Total neoadjuvant treatment (TNT) and immunotherapy are two major issues in the treatment of LARC. In the two latest phase III randomized controlled trials (RAPIDO and PRODIGE23), the TNT approach achieved higher rates of pathologic complete response and distant metastasis-free survival than conventional chemoradiotherapy. Phase I/II clinical trials have reported promising response rates to neoadjuvant (chemo)-radiotherapy combined with immunotherapy. Accordingly, the treatment paradigm for LARC is shifting toward methods that increase the oncologic outcomes and organ preservation rate. However, despite the progress of these combined modality treatment strategies for LARC, the radiotherapy details in clinical trials have not changed significantly. To guide future radiotherapy for LARC with clinical and radiobiological evidence, this study reviewed recent neoadjuvant clinical trials evaluating TNT and immunotherapy from a radiation oncologist's perspective.

Complete response with combined therapy in a patient with brain metastasis from nasopharyngeal carcinoma: case report and literature review

Brain metastasis of nasopharyngeal carcinoma (NPC) is a rare event with limited research. In this report, we discuss the details of a case of brain metastasis from NPC that presented with a solitary, cystic lesion in the frontal lobe. We also reviewed the related literature published in the last 20 years. We analyzed the patient's clinical characteristics, which indirectly suggested hematogenous spread rather than a cerebrospinal fluid route. Although there are no standard treatments for brain metastasis of NPC, previous studies reported that combined surgery and radiotherapy was a good treatment option, with long survival. Our patient achieved intracranial complete response after the combination of conventional chemoradiotherapy and novel immunotherapy. This treatment option could be useful in future similar cases.

New phase therapeutic pursuits for targeted drug delivery in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is known as the most aggressive and prevalent brain tumor with a high mortality rate. It is reported in people who are as young as 10 years old to as old as over 70 years old, exhibiting inter and intra tumor heterogeneity. There are several genomic and proteomic investigations that have been performed to find the unexplored potential targets of the drug against GBM. Therefore, certain effective targets have been taken to further validate the studies embarking on the robustness in the field of medicinal chemistry followed by testing in clinical trials. Also, The Cancer Genome Atlas (TCGA) project has identified certain overexpressed targets involved in the pathogenesis of GBM in three major pathways, i.e., tumor protein 53 (p53), retinoblastoma (RB), and receptor tyrosine kinase (RTK)/rat sarcoma virus (Ras)/phosphoinositide 3-kinase (PI3K) pathways. This review focuses on the compilation of recent developments in the fight against GBM thus, directing future research into the elucidation of pathogenesis and potential cure for GBM. Also, it highlights the potential biomarkers that have undergone extensive research and have promising prognostic and predictive values. Additionally, this manuscript analyses the advent of gene therapy and immunotherapy, unlocking the way to consider treatment approaches other than, or in addition to, conventional chemo-radiation therapies. This review study encompasses all the relevant research studies associated with the pathophysiology, occurrence, diagnostic tools, and therapeutic intervention for GBM. It highlights the evolution of various therapeutic perspectives against GBM from the most conventional form of radiotherapy to the recent advancement of gene/cell/immune therapy. Further, the review focuses on various targeted therapies for GBM including chemotherapy sensitization, radiotherapy, nanoparticles based, immunotherapy, cell therapy, and gene therapy which would offer a comprehensive account for exploring several facets related to GBM prognostics.

ERK inhibitor: A candidate enhancing therapeutic effects of conventional chemo-radiotherapy in esophageal squamous cell carcinoma

For patients with esophageal squamous cell carcinoma (ESCC), standard therapeutic methods (cisplatin and radiotherapy) have been found to be ineffective and severely toxic. Targeted therapy emerges as a promising solution for this dilemma. It has been reported that targeted therapies are applied alone or in combination with standard conventional therapies for the treatment of a variety of cancers. To the best of our knowledge, in patients with ESCC, the combinational methods containing standard therapy and ERK-targeted therapy have yet to be explored.To analyze the prognostic role of p-ERK in ESCC patients, the Kaplan-Meier analysis and Cox regression model were used. To assess the effects of ERK-targeted therapy (GDC0994) on ESCC cells, in vitro studies including CCK-8 assay, colony formation assay, and scratch wound healing assay were conducted. In addition, the changes in cell cycle distribution and apoptosis were analyzed by flow cytometry. Besides, to assess the efficacy of different therapies in vivo, the xenograft tumor models were established by subcutaneously inoculating tumor cells into the flank/leg of mice.In patients with ESCC, a strong correlation between the high expression level of p-ERK and the poor prognosis (p < 0.01, Log-Rank test) has been identified. By analyzing the results from CCK-8 and scratch wound healing assays, we demonstrated that the ERK inhibitor repressed the viability and migration of ESCC cells. In addition, following the treatment of GDC0994, the volumes of xenograft tumors significantly decreased (p < 0.001, one-way ANOVA). Furthermore, blocking the mitogen-activated protein kinase (MAPK/ERK) pathway enhanced the therapeutic efficacy of both cisplatin and radiotherapy (p < 0.05). These findings imply the role of p-ERK in the prognosis of ESCC patients and the therapeutic value of ERK inhibitors in ESCC.

Novel Nano-Drug Delivery System for Brain Tumor Treatment

As the most dangerous tumors, brain tumors are usually treated with surgical removal, radiation therapy, and chemotherapy. However, due to the aggressive growth of gliomas and their resistance to conventional chemoradiotherapy, it is difficult to cure brain tumors by conventional means. In addition, the higher dose requirement of chemotherapeutic drugs caused by the blood-brain barrier (BBB) and the untargeted nature of the drug inevitably leads to low efficacy and systemic toxicity of chemotherapy. In recent years, nanodrug carriers have attracted extensive attention because of their superior drug transport capacity and easy-to-control properties. This review systematically summarizes the major strategies of novel nano-drug delivery systems for the treatment of brain tumors in recent years that cross the BBB and enhance brain targeting, and compares the advantages and disadvantages of several strategies.

Isotoxic High-Dose Stereotactic Body Radiotherapy (iHD-SBRT) Versus Conventional Chemoradiotherapy for Localized Pancreatic Cancer: A Single Cancer Center Evaluation.

Given the lack of direct comparative evidence, we aimed to compare the oncological outcomes of localized pancreatic ductal adenocarcinoma (PDAC) treated in the same tertiary cancer center with isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT) or conventional chemoradiotherapy (CRT). Biopsy-proven borderline/locally advanced patients treated with iHD-SBRT (35 Gy in 5 fractions with a simultaneous integrated boost up to 53 Gy) or CRT (45-60 Gy in 25-30 fractions) were retrospectively included from January 2006 to January 2021. The median overall survival (mOS) was evaluated trough uni- and multivariate analyses. The progression free survival (PFS) and the 1-year local control (1-yLC) were also reported. Eighty-two patients were included. The median follow-up was 19.7 months. The mOS was in favour of the iHD-SBRT group (22.5 vs. 15.9 months, p &lt; 0.001), including after multivariate analysis (HR 0.39 [CI95% 0.18-0.83], p = 0.014). The median PFS and the 1-yLC were also significantly better for iHD-SBRT (median PFS: 16.7 vs. 11.5 months, p = 0.011; 1-yLC: 75.8 vs. 39.3%, p = 0.004). In conclusion, iHD-SBRT is a promising RT option and may offer an improvement in OS in comparison to CRT for localized PDAC. Further validation is required to confirm the exact role of iHD-SBRT and the optimal therapeutic sequence for the treatment of localized PDAC.

Recurrent posterior fossa group A (PFA) ependymoma in a young child with constitutional mismatch repair deficiency (CMMRD).

Recurrent posterior fossa group A (PFA) ependymoma in a young child with constitutional mismatch repair deficiency (CMMRD).

The Emergence of Cancer Stem Cells in Early Diagnosed Prostate Cancer

The Emergence of Cancer Stem Cells in Early Diagnosed Prostate Cancer

Dose and Fractionation Effects on Lymphocyte-Sparing after Stereotactic Body Radiation Therapy in Patients with Pancreatic Cancer

<h3>Purpose/Objective(s)</h3> Radiation-induced lymphopenia (RIL) is caused by exposing the blood pool to radiation therapy and is associated with inferior survival in patients with pancreatic cancer (PC). Dose escalation with stereotactic body radiation therapy (SBRT) is associated with decreased severity of RIL and improved survival compared to conventional chemoradiation, however, there is also increasing appreciation for the need for larger field sizes to treat occult microscopic disease. We retrospectively analyzed patients undergoing SBRT for PC to explore if the number of fractions, BED10 dose, and PTV volume correlated with lymphopenia. <h3>Materials/Methods</h3> Total lymphocyte counts (TLCs) were compared before and up to 2 months after SBRT for 139 patients treated with SBRT for PC at two institutions. Univariate and multivariate analyses (MVA) were used to identify associations between TLC and G2+ lymphopenia (<800/mm^3), number of fractions, total BED10, and PTV. Baseline TLC were compared using Kruskal-Wallis test. PTV threshold for G2+ RIL was determined with receiver operating characteristic analysis. <h3>Results</h3> Median BED10 was 54.8Gy (48-100) (Table 1). Median baseline and post-SBRT ALC were 1.6/uL (0.59-6.09) and 0.85/uL (0.18-1.99), respectively. All groups had similar median baseline TLCs (p=0.567). G2+ lymphopenia was seen in 49/139 (35%) patients after SBRT. Median planning target volume (PTV) and tumor diameter was 85.5 (11.5-381.6) cm³ and 2.5 (0.3-7.8) cm³. On MVA, only PTV volume was associated with decrease in ALC (95% CI 0.24 - 0.95; P=0.001) and with G2+ lymphopenia (95% CI 1.2-12.9; p=0.019). G2+ lymphopenia was more common with PTV ≥ 178 cm^3 (P<0.01). There was no association between ALC or G2+ lymphopenia and age, gender, tumor diameter, tumor location, BED10, treatment with 5 vs 3 fractions, or treatment with 50 Gy in 5 fractions versus 36-39 Gy in 3 fractions. <h3>Conclusion</h3> While previous studies have shown that SBRT has improved RIL compared to conventional CRT, this effect appears to be independent of SBRT fractionation and total BED, but dependent on PTV size, a surrogate for the volume of lymphocytes exposed to RT. Given the association of severe RIL with survival in LAPC, our study suggests that PTV volume may drive development of lymphopenia and survival. Therefore, we demonstrate the need to balance the lymphopenia effect by limiting PTV size with SBRT with expansion of PTVs to include elective nodes at risk of harboring microscopic disease.

Dosimetric predictors of toxicity in a randomized study of short-course vs conventional radiotherapy for glioblastoma

PurposeThere is no consensus on appropriate organ at risk (OAR) constraints for short-course radiotherapy for patients with glioblastoma. Using dosimetry and prospectively-collected toxicity data from a trial of short-course radiotherapy for glioblastoma, this study aims to empirically examine the OAR constraints, with particular attention to left hippocampus dosimetry and impact on neuro-cognitive decline. Methods and MaterialsData was taken from a randomized control trial of 133 adults (age 18–70 years; ECOG performance score 0–2) with newly diagnosed glioblastoma treated with 60 Gy in 30 (conventional arm) versus 20 (short-course arm) fractions of adjuvant chemoradiotherapy (ClinicalTrials.gov Identifier: NCT02206230). The delivered plan’s dosimetry to the OARs was correlated to prospective-collected toxicity and Mini-Mental State Examination (MMSE) data. ResultsToxicity events were not significantly increased in the short-course arm versus the conventional arm. Across all OARs, delivered radiation doses within protocol-allowable maximum doses correlated with lack of grade ≥ 2 toxicities in both arms (p < 0.001), while patients with OAR doses at or above protocol limits correlated with increased grade ≥ 2 toxicities across all examined OARs in both arms (p-values 0.063–0.250). Mean left hippocampus dose was significantly associated with post-radiotherapy decline in MMSE scores (p = 0.005), while the right hippocampus mean dose did not reach statistical significance (p = 0.277). Compared to the original clinical plan, RapidPlan left hippocampus sparing model decreased left hippocampus mean dose by 43 % (p < 0.001), without compromising planning target volume coverage. ConclusionsIn this trial, protocol OAR constraints were appropriate for limiting grade ≥ 2 toxicities in conventional and short-course adjuvant chemoradiotherapy for glioblastoma. Higher left hippocampal mean doses were predictive for neuro-cognitive decline post-radiotherapy. Routine contouring and use of dose constraints to limit hippocampal dose is recommended to minimize neuro-cognitive decline in patients with glioblastoma treated with chemoradiotherapy.

Brachytherapy via a depot of biopolymer-bound 131I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours.

Locally advanced pancreatic tumours are highly resistant to conventional radiochemotherapy. Here we show that such resistance can be surmounted by an injectable depot of thermally responsive elastin-like polypeptide (ELP) conjugated with iodine-131 radionuclides (131I-ELP) when combined with systemically delivered nanoparticle albumin-bound paclitaxel. This combination therapy induced complete tumour regressions in diverse subcutaneous and orthotopic mouse models of locoregional pancreatic tumours. 131I-ELP brachytherapy was effective independently of the paclitaxel formulation and dose, but external beam radiotherapy (EBRT) only achieved tumour-growth inhibition when co-administered with nanoparticle paclitaxel. Histological analyses revealed that 131I-ELP brachytherapy led to changes in the expression of intercellular collagen and junctional proteins within the tumour microenvironment. These changes, which differed from those of EBRT-treated tumours, correlated with the improved delivery and accumulation of paclitaxel nanoparticles within the tumour. Our findings support the further translational development of 131I-ELP depots for the synergistic treatment of localized pancreatic cancer.

Influence of chemoradiation on the immune microenvironment of cervical cancer patients

PurposeCervical cancer remains a leading cause of cancer death in women. While immunotherapy has shown great success in combating cancer, the value of immunotherapy in cervical cancer is still only beginning to be explored. Thus, we performed a prospective analysis of patient blood and tumor samples at the beginning and end of conventional chemoradiation to assess changes in the immune cell and immunoreceptor compartments, and investigate if and when the addition of immunotherapy could be beneficial.MethodsPatients with FIGO II–III cervical cancer receiving standard chemoradiation between January 2020 and December 2021 were included. We collected tumor and blood samples from patients before and at the end of therapy and analyzed immune cell composition and immune checkpoint receptor expression on both immune and tumor cells using multicolor flow cytometry.ResultsIn all, 34 patients were eligible in the study period; 22 could be included and analyzed in this study. We found that chemoradiation significantly reduces T cell numbers in both tumors and blood, but increases macrophage and neutrophil numbers in tumors. Furthermore, we found that the percentage of immune checkpoint receptor PD‑1 and TIGIT-expressing cells in tumors was significantly reduced at the end of therapy and that CD4 and CD8 memory T cell populations were altered by chemoradiation. In addition, we observed that while PD-L1 expression intensity was upregulated by chemoradiation on blood CD8 cells, PD-L1 expression frequency and the expression intensity of antigen-presenting molecule MHC‑I were significantly reduced on tumor cells.ConclusionOur data demonstrate that chemoradiation significantly alters the immune cell composition of human cervical tumors and the expression of immune checkpoint receptors on both lymphocytes and tumor cells. As our results reveal that the percentage of PD‑1+ CD8 cells in the tumor as well as the frequency of PD-L1-expressing tumor cells were reduced at the end of therapy, neoadjuvant or simultaneous anti-PD‑1 or anti-PD-L1 treatment might provide better treatment efficiency in upcoming clinical studies.

TREATMENT OUTCOME AND TOXICITY OF HYPOFRACTIONATED RADIOTHERAPY WITH CONCOMITANT CHEMOTHERAPY VERSUS CONVENTIONAL FRACTIONATED CONCOMITANT CHEMORADIATION IN LOCALLY ADVANCED HEAD-AND-NECK CARCINOMA: A COMPARATIVE STUDY

Objectives: In our study, radiation of a higher dose per fraction (2.75 Gy/fraction, total dose of 55 Gy/20 fractions/4 weeks) with concomitant chemotherapy was compared with conventional chemoradiation (2 Gy/fraction, a total dose of 66 Gy/33 fractions/6 and half weeks, with concomitant chemotherapy), in patients of locally advanced squamous cell carcinomas of head and neck in terms of efficacy and toxicities. Methods: A total of 75 patients registered at the Department of Radiotherapy, NRS Medical College and Hospital, Kolkata, were allotted in two arms chronologically in a 1:1 ratio. Arm A – Patients received hypofractionated radiotherapy, 55 Gy/20 fractions in 4 weeks with concomitant weekly cisplatin (40 mg/m2). Arm B – Patients received conventional radiotherapy, 66 Gy/33 fractions in 6½ weeks with concomitant weekly cisplatin (40 mg/m2). Results: Both in terms of efficacy and toxicities, the hypofractionation arm was comparable to the conventional arm, and no statistically significant difference was present between the arms. For the study arm, complete response was 56.6%, partial response was 36.6%, and for control arm, complete response 50% and partial response 37.5% (p=0.750). In terms of acute toxicities and late dysphagia, both the arms were almost similar. Conclusion: The hypofractionated regimen was associated with tolerable acute and late toxicities and satisfactory local control. Considering the patient load, the overall treatment time, and the cost of hospital stay, this hypofractionated regimen is a good treatment option in our low-resource setup.

Epidemiology, Detection, and Management of Pancreatic Cancer

PC (Pancreatic Cancer) is that the fourth most common cause of death due to cancer worldwide. The incidence and mortality rates are increasing year by year worldwide, and this review has analyzed the foremost recent incidence and mortality data for pancreatic cancer occurrence in India. Several possible risk factors are discussed here, involving known established risk factors and novel possible risk factors. The development of this cancer may be a stepwise progression through intraepithelial neoplasia to carcinoma. Though early and accurate diagnosis is promising based on a combination of recent techniques including tumor markers and imaging modalities, lacking early clinical symptoms makes the diagnosis late. Pancreatic cancer is often difficult to diagnose. This is because there are no validated, specific screening tests that can easily and reliably find early-stage pancreatic cancer in people who do not show symptoms. Furthermore, people with pancreatic cancer often do not have clearly identified symptoms in the early stages of the disease. This means it is often not found until later stages when the cancer can no longer be removed with surgery and/or has spread from the pancreas to other parts of the body. Correct staging is critical because treatment is usually based on this parameter. Treatment options have improved throughout the last decades. However, surgical excision remains the first therapy and efficacy of conventional chemo-radiotherapy for PC is limited. Recently, some novel new therapies are developed and can be applied in clinics soon. This review will provide a summary of pancreatic cancer, including an understanding of the developments and controversies.

Inflammatory myofibroblastic tumor of intestine presenting as intussusception

Inflammatory myofibroblastic tumor (IMFT) is a rare mesenchymal tumor predominantly seen in the lungs. Intestinal IMFT is extremely rare and may cause intussusception. Surgery is the mainstay of treatment as IMFTs are resistant to conventional chemoradiation. Long term follow up is required as there is high recurrence risk. About 50% of IMFTs have translocations involving the anaplastic lymphoma kinase (ALK) gene which has been therapeutically targeted using Crizotinib. We report a 1-year-old boy with ileo-ileal intussusception who was operated after a trial of conservative management. Laparotomy revealed an ileal mass that was resected and histopathology confirmed IMFT. Recovery was uneventful.

Long-term follow-up results of the effects of chronotherapy and conventional chemotherapy combined with intensity modulated radiotherapy on dendritic cells and lymphocyte subsets in nasopharyngeal carcinoma.

e18066 Background: In this study, we compared the effects of chronotherapy with conventional chemotherapy plus intensity modulated radiotherapy (IMRT)on dendritic cells and lymphocyte subsets in locoregionally advanced NPC. Methods: Analysis of 136 patients with treatment locoregionally advanced nasopharyngeal carcinoma enrolled, 68 patients were randomly assigned to the chronotherapy group and 68 patients to the conventional chemotherapy group, and all patients received 2-3 cycles of TPF induction chemotherapy plus 2-3 cycles of cisplatin concurrent chemoradiotherapy with the following schedules: docetaxel (DOC): 60mg / m2, ivgtt, D1 (03:30-04:30); Cisplatin (DDP): 60mg / m2, civ, d1-d5 (10:00-22:00); 5-fluorouracil (5-FU): 600mg / m2 / D 1, civ, d1-d5 (22:00-10:00); Synchronized DDP 100mg / m2, civ, D1 (10:00-22:00). Conventional group: Doc 60 mg / m2, ivgtt, D1; DDP 60mg/m2, ivgtt, d1; 5-FU 600mg/m2 /d 1, civ, d1-d5(120h); Synchronized DDP 100mg / m2, IVGTT, D1. Both groups were treated with IMRT at the same dose。 Lymphocyte and lymphocyte subsets were measured by flow cytometry before induction chemotherapy and 1 year versus 3 years after the end of concurrent chemoradiotherapy in patients, and changes in immune parameters, survival, and long-term toxicities were compared between the two groups. Results: One year after induction chemotherapy and concurrent chemoradiotherapy, the chronotherapy group showed higher plasma dendritic cells (PDC) than the conventional group (P &lt; 0.05). At 1 year after induction chemotherapy and concurrent chemoradiotherapy, CD4 +, activated CD4 +, activated CD8 +, CD3-CD16 +, PDC, and MDC were significantly higher (P &lt; 0.05) in both pre - and post-treatment groups, and at 1 year after induction chemotherapy and concurrent chemoradiotherapy in the conventional group (P &lt; 0.05). At 3 years after induction chemotherapy and concurrent chemoradiotherapy, CD4 +, activated CD4 +, activated CD8 +, CD4 + CD25 +, cd3-cd19 +, and CD3-CD16 + were significantly increased in the chronic group (P &lt; 0.05), and CD4 +, activated CD4 +, activated CD8 +, and CD4 + CD25 + were significantly increased in the conventional group (P &lt; 0.05). In the comparison of toxic effects between the two groups, the incidences of xerostomia and dysphagia in the group at 3 years after treatment were significantly lower than those in the conventional group (P &lt; 0.05). There were no significant differences in PFS, OS, DMFS, LRRFS between the two groups at 3 years (P &gt; 0.05). Conclusions: Chronotherapy with intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma more than conventional chemoradiotherapy reduces damage to dendritic cells and lymphocytes and alleviates toxic effects such as xerostomia and dysphagia at the same survival rate.