Combined Modality Treatment Research Articles

Re-irradiation combined with bevacizumab for recurrent glioblastoma beyond bevacizumab failure: survival outcomes and prognostic factors

The combination of re-irradiation and bevacizumab has emerged as a potential therapeutic strategy for patients experiencing their first glioblastoma multiforme (GBM) recurrence. This study aims to assess the effectiveness of the re-irradiation and bevacizumab combination in treating second-progression GBM patients who are resistant to bevacizumab monotherapy. This retrospective study enrolled 64 patients who developed a second progression after single-agent bevacizumab therapy. The patients were divided into two groups: 35 underwent best supportive care (none-ReRT group), and 29 received bevacizumab and re-irradiation (ReRT group). The study measured the overall survival time after bevacizumab failure (OST-BF) and re-irradiation (OST-RT). Statistical tests were used to compare categorical variables, evaluate the difference in recurrence patterns between the two groups, and identify optimal cutoff points for re-irradiation volume. The results of the Kaplan–Meier survival analysis indicated that the re-irradiation (ReRT) group experienced a significantly higher survival rate and longer median survival time than the non-ReRT group. The median OST-BF and OST-RT were 14.5 months and 8.8 months, respectively, for the ReRT group, while the OST-BF for the none-ReRT group was 3.9 months (p < 0.001). The multivariable analysis identified the re-irradiation target volume as a significant factor for OST-RT. Moreover, the re-irradiation target volume exhibited excellent discriminatory ability in the area under the curve (AUC) analysis, with an optimal cutoff point of greater than 27.58 ml. These findings suggest that incorporating re-irradiation with bevacizumab therapy may be a promising treatment strategy for patients with recurrent GBM resistant to bevacizumab monotherapy. The re-irradiation target volume may serve as a valuable selection factor in determining which patients with recurrent GBM are likely to benefit from the combined re-irradiation and bevacizumab treatment modality.

RADIOTHERAPY BRIDGING IN LARGE B‐CELL LYMPHOMA PATIENTS RECEIVING CD19 CAR‐T – THE UK EXPERIENCE

Background: Radiotherapy (RT) has potential synergistic effects with CAR T but is not widely used as bridging therapy for lymphoma patients due to logistical challenges, uncertainty about patient selection and lack of standardised protocols. Published data on RT bridging are so far restricted to single-centre analyses. Methods: We analysed RT bridging in a large multi-centre national cohort of large B-cell lymphoma (LBCL) patients approved for 3rd line axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) between December 2018 and October 2022 across 12 UK centres. Results: Of 763 approved patients, 722 (95%) were leukapheresed, 717 had data available on bridging therapy. 170/717 (24%) received RT bridging, 129 as single modality and 41 as combined modality treatment (CMT). Use of RT bridging varied between centres from 11% to 32%, and increased from 19% (2018–19) to 26% (2021–22; p = 0.034). Median age of RT bridged patients was 60 y. 69% had de novo LBCL, 8% PMBL, 35% tFL and 6% transformed from other low-grade lymphoma. Disease characteristics for RT bridged patients with available data were as follows: 66% advanced stage, 41% bulk, 87% elevated LDH, 42% IPI ≥ 3, 17% double/triple hit. Patients given single modality RT were less likely to have advanced stage or ≥2 extranodal sites versus those receiving systemic therapy/CMT (61% vs. 85/83% and 18% vs. 30/39%, respectively; p < 0.05). Median time from approval to infusion was 56 days with no difference between bridging modalities. Infusion rates were 88% for RT bridging (vs. 84%, 85%, 85% for no bridging, steroids, or systemic therapy, respectively (p = 0.41)). Data on bridging (in-field) response was available for 46 RT patients: 10% CR, 65% PR, 6% SD, 10% PD. Details on RT techniques, anatomical locations and toxicities were available for 68 patients and will be provided at the meeting. Doses of 2–39 Gy were used, including combination of multiple doses; 40 patients received IMRT. Only one patient experienced G3–4 toxicity from RT. The overall incidence of G ≥ 3 CRS was 5.2% and G ≥ 3 ICANS 16.3%, with no significant difference according to bridging approaches. Median follow-up was 16 months. RT bridged patients had favourable outcomes with 1-y PFS of 56% for single modality and 47% for CMT, and 1-y OS of 65% and 56%, respectively (Figure 1). RT bridging was associated with favourable outcomes both in limited and advanced stage (1-y PFS 59% (43—72) and 50% (39–61), respectively. Keywords: aggressive B-cell non-Hodgkin lymphoma, cellular therapies, radiation therapy Conflicts of interests pertinent to the abstract A. Kuhnl Consultant or advisory role: Kite/Gilead, Novartis, BMS Honoraria: Kite/Gilead, Novartis A. Kirkwood Honoraria: Kite/Gilead A. Gibb Consultant or advisory role: Kite/Gilead A. Latif Honoraria: Kite/Gilead, Novartis

Baseline‐PET derived metrics are the most relevant factors for risk stratification in early‐stage nonbulky HL: preliminary results of the RAFTING trial

Introduction: The efficacy of combined-modality treatment (Tx) with chemotherapy (CT) and radiotherapy (RT) in early-stage Hodgkin Lymphoma (eHL) is offset by long-term morbidity, with a cumulative incidence of 2nd primary malignancy at 40 years of 48.5% (Schaapveld 2015). The RAFTING trial (NCT Id. 04866654) is a phase-2 prospective single-cohort international study to explore the effectiveness of a risk-adapted Tx in non-bulky stage I-IIA eHL, based on the risk of CT failure (TxF) in a single-patient (p.) basis and in a personalized medicine design. Methods: p. are first stratified in 3 classes of TxF risk, depending on (a) modified EORTC criteria (m-EORTC), in which bulky is replaced by a Large Nodal Mass (LNM), defined by a longest ∅ measuring ≥5 cm in CT or PET/CT, (b) Metabolic Tumor Volume (MTV), with a SUVmax threshold method of 41% and cutoff value of 84 ml, and (c) PET-2 result (5-point scale). Tx stratification: Group 1: PET-2 neg. & low MTV p., treated either with 2 (group 1a) or 4 (group 2b) ABVD depending on no or ≥1 m-EORTC criterion presence, addressed, once in CR, to a 3-monthly cell-free tumor DNA (ctDNA) assay (CAPPSeq. Method, Spina 2018); Group 2: group 1 p. with < CR after ABVD or in “limited” relapse (LR), defined by eHL relapse in old and up to 3 new nodal areas, addressed to Involved-Node RT (INRT) and Nivolumab (N), 240 mg. i.v. twice a month for 24 doses; Group 3: PET-2+ and/or high MTV p., treated with the triplet ABVD × 4, INRT, 20 or 30 Gy (A-RxT-N). All PET/CT scans are centrally reviewed by an expert panel. The trial primary endpoint is a 3-Y PFS ≥90% in group 1 p. The secondary endpoints are: (a) Effectiveness of RxT (36 Gy) and N (same schedule of Group 3), in rescue p. with LR (b) effectiveness of the triplet A-RxT-N in high-risk (Group 3) eHL; (c) predictive value of ctDNA in detecting an impending eHL relapse after CT alone. Results: Preliminary results of risk stratification upon enrolment of the first 104/180 (58%) of the pre-planned sample size: in a per-protocol analysis, 88/104 (85%) turned out eligible and 73 stratified for risk. Non-eligibility reasons were higher HL stage, or bulky (10 p.) and early Tx stop, for p./investigator decision: (6p.). Out of 73 p. stratified, 53 (73%) were low-risk (Group 1), and 20 (27%) high risk (Group 3). Out of 53 low-risk p., 16 were in Group 1a: one of them was addressed to salvage Tx with ASCT because of an extended relapse 3 months after CT end. As many as 37 (70%) of low-risk p. belonged to Group 1b, mostly because of the presence of a LNM; two of them had a LR (entering Group 2) and started RxT-N rescue. Twenty p. (27%) had high-risk disease, most (14) for a high MTV, and a minority (6) for a positive PET-2. Updated results will be presented. The research was funded by: Polish Medical Agency ABM Ongoing Trial Keywords: Liquid biopsy, Ongoing Trials, PET-CT No conflicts of interests pertinent to the abstract.

Research Advances in the Treatment of Riehl's Melanosis.

Riehl's melanosis (RM) is a contact photodermatitis, with fast progressive gray-brown skin pigmentation as the main manifestation, which can seriously affect the psychology and physiology of patients. Currently, although the etiological factors of Riehl's melanosis is still be unknown, the existing literature proves clearly the cause of it is related to the contacting with suspected allergens. For decades, there has been no standard method for the treatment of RM, but with both conventional drug therapy and laser therapy having been attempted. Topical application of bleaching agents is mainly used as an auxiliary treatment modality. The laser treatment modality remains a hot spot, among which Q-switched Nd:YAG laser is well received for RM. Positive outcomes have been achieved by the combined treatment modalities attempted in recent years also achieve positive outcomes. The purpose of this paper is to review and summarize recent advances in the treatment of the disease.

Outcome and patterns of relapse in primary gastric diffuse large B cell lymphoma treated with RCHOP

ABSTRACTObjectivesPatterns and predictors of relapse in primary gastric diffuse large B cell lymphoma (DLBCL) were variably reported. Our study aims to evaluate the patterns and predictors of relapse in early-stage gastric DLBCL treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone (RCHOP).MethodsFrom 2005 to 2019, the medical records of 72 patients with stage I or stage II gastric DLBCL treated with six cycles of RCHOP without radiotherapy were reviewed. Different variables were correlated with progression free survival (PFS), overall survival (OS), and local relapse free survival (LRFS).Results64 (88.1%) patients achieved a complete response (CR), while 8 (11.9%) had refractory disease. After CR, 9 (14%) patients relapsed; 7 (78%) relapses were loco-regional. Abnormal LDH (p = 0.028), H. pylori negative (p = 0.032) and, stage adjusted international prognostic index (sa-IPI) > 1 (p = 0.013) correlated with loco-regional failure. The 5-year PFS, OS, and LRFS were 74.8%, 75.3%, and 87.5%, respectively, after a median follow-up of 58 (range: 6–185) months. The median time to progression or relapse was 9 months (range: 5–54 months). In multivariate analysis, a sa-IPI >1 (HR: 3.56, CI: 1.35–8.8, p = 0.01) was associated with PFS while low albumin (HR: 8.85, CI: 1.09–71.4, p = 0.041) was associated with worse OS. None of the variables were associated with LRFS.ConclusionTreatment of primary gastric DLBCL with RCHOP results in a high CR rate. The majority of treatment failures were loco-regional. Sa-IPI and H. pylori status may be used to identify patients who may benefit from combined modality treatment.

Revisiting the predictive role of 18F-fluorodeoxyglucose positron emission tomography/computerized tomography on treatment outcome in early-stage favorable Hodgkin lymphoma.

In the present manuscript Gallamini et al. comment the results of three large, phase III, randomized clinical trials in early-stage favorable Hodgkin Lymphoma (HL), aimed at exploring the non-inferiority of ABVD chemotherapy alone compared to combined-modality treatment with ABVD and Involved Field/Node Radiotherapy (INRT). The authors also report the preliminary results of risk-stratification in the first 60 enrolled patients in the phase 2, prospective, international study RAFTING: RAdiotherapy Free Treatment IN Good-prognosis early-stage HL (National Trial Identifier 04866654). In this trial patients are stratified, before treatment onset, according to the risk of therapy failure in a single patient basis, taking into account non only the results of interim and End-of-Therapy PET, but also the value of new metrics extracted from the baseline PET/CT such as the Large Nodal Mass (LNM) and Total Metabolic Tumor Volume (TMTV). Treatment intensity, consisting in ABVD chemotherapy, INRT and Nivolumab maintenance, is modulated on the presence/absence of the above factors, in a personalized-medicine approach. The most frequently detected factors driving treatment intensity were LNM and TMTV, while the results of interim and end-of-treatment PET were also determinant, albeit in a lower percentage of cases.

Brain Scans May Offer Clues About Depression Remission

Brain Scans May Offer Clues About Depression Remission

Primary Diffuse Large B-Cell Lymphoma of the Bone

Primary lymphoma of the bone (PLB) is a rare lymphoproliferative neoplasm that can present either as solitary or multiple bone lesions. We report four patients with PLB who were successfully treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by consolidative radiotherapy. All patients achieved a complete remission and had excellent long-term outcomes. PLB has a favorable response to combined modality treatment with chemoimmunotherapy and radiation. Long-term outcomes of PLB tend to be better than those of non-osseous diffuse large B-cell lymphoma.

Perfluorocarbon nanodrug induced oxygen self-enriching sonodynamic therapy improves cancer immunotherapy after insufficient radiofrequency ablation.

Residual lesions and undetectable metastasis after insufficient radiofrequency ablation (iRFA) are associated with earlier new metastases and poor survival in cancer patients, for induced aggressive tumor phenotype and immunosuppression. Programmed cell death protein 1(PD-1) blockade has been reported to enhance the radiofrequency ablation-elicited antitumor immunity, but its ability to eliminate incompletely ablated residual lesions has been questioned. Here, we report a combined treatment modality post iRFA based on integrating an oxygen self-enriching nanodrug PFH-Ce6 liposome@O2 nanodroplets (PCL@O2)-augmented noninvasive sonodynamic therapy (SDT) with PD-1 blockade. PCL@O2 containing Ce6 as the sonosensitizer and PFH as O2 reservoir, was synthesized as an augmented SDT nanoplatform and showed increased ROS generation to raise effective apoptosis of tumor cells, which also exposed more calreticulin to induce stronger immunogenic cell death (ICD). Combining with PD-1 blockade post iRFA, this optimized SDT induced a better anti-tumor response in MC38 tumor bearing mouse model, which not only arrested residual primary tumor progression, but also inhibited the growth of distant tumor, therefore prolonging the survival. Profiling of immune populations within the tumor draining lymph nodes and tumors further revealed that combination therapy effectively induced ICD, and promoted the maturation of dendritic cells, tumor infiltration of T cells, as well as activation of cytotoxic T lymphocytes. While iRFA alone could result in an increase of regulatory T cells (Tregs) in the residual tumors, SDT plus PD-1 blockade post iRFA reduced the number of Tregs in both primary and distant tumors. Moreover, the combined treatment could significantly initiate long-term immune memory, manifesting as elevated levels of CD8+ and CD4+ central memory cells. Therefore, this study establishes the preclinical proof of concept to apply oxygen self-enriching SDT to augment cancer immunotherapy after iRFA.

Elevated temperatures and longer durations improve the efficacy of oxaliplatin- and mitomycin C-based hyperthermic intraperitoneal chemotherapy in a confirmed rat model for peritoneal metastasis of colorectal cancer origin.

In patients with limited peritoneal metastasis (PM) originating from colorectal cancer, cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a potentially curative treatment option. This combined treatment modality using HIPEC with mitomycin C (MMC) for 90 minutes proved to be superior to systemic chemotherapy alone, but no benefit of adding HIPEC to CRS alone was shown using oxaliplatin-based HIPEC during 30 minutes. We investigated the impact of treatment temperature and duration as relevant HIPEC parameters for these two chemotherapeutic agents in representative preclinical models. The temperature- and duration- dependent efficacy for both oxaliplatin and MMC was evaluated in an in vitro setting and in a representative animal model. In 130 WAG/Rij rats, PM were established through i.p. injections of rat CC-531 colon carcinoma cells with a signature similar to the dominant treatment-resistant CMS4 type human colorectal PM. Tumor growth was monitored twice per week using ultrasound, and HIPEC was applied when most tumors were 4-6mm. A semi-open four-inflow HIPEC setup was used to circulate oxaliplatin or MMC through the peritoneum for 30, 60 or 90 minutes with inflow temperatures of 38°C or 42°C to achieve temperatures in the peritoneum of 37°C or 41°C. Tumors, healthy tissue and blood were collected directly or 48 hours after treatment to assess the platinum uptake, level of apoptosis and proliferation and to determine the healthy tissue toxicity. In vitro results show a temperature- and duration- dependent efficacy for both oxaliplatin and MMC in both CC-531 cells and organoids. Temperature distribution throughout the peritoneum of the rats was stable with normothermic and hyperthermic average temperatures in the peritoneum ranging from 36.95-37.63°C and 40.51-41.37°C, respectively. Treatments resulted in minimal body weight decrease (<10%) and only 7/130 rats did not reach the endpoint of 48 hours after treatment. Both elevated temperatures and longer treatment duration resulted in a higher platinum uptake, significantly increased apoptosis and lower proliferation in PM tumor lesions, without enhanced normal tissue toxicity. Our results demonstrated that oxaliplatin- and MMC-based HIPEC procedures are both temperature- and duration-dependent in an in vivo tumor model.

Management of limited stage Hodgkin lymphoma

Hodgkin lymphoma (HL) is a lymphoid neoplasm characterized by malignant lymphocytes, known as Reed-Sternberg cells, on a background of non-neoplastic inflammatory cells. Lugano staging determines the stage of Hodgkin lymphoma, which, in turn, determines the treatment and prognosis. Limited-stage disease is defined as Stage I and Stage II, which is diagnosed in more than 50% of patients. Pre-treatment risk stratification, PET-adapted therapy, and combined modality treatment have significantly improved cure rates, making limited-stage HL one of the most curable malignancies. In this article, we discuss the current approach to managing limited-stage HL.

Combined modality treatment of operable breast cancer using intraoperative radiotherapy

Objective of the study: To review worldwide literature data on the efficacy of combined modality treatment including intraoperative radiation therapy (IORT) in patients with operable breast cancer (BC). Material and Мethods. Of 110 publications (2000–2021) available from Scopus, Pubmed, Elibrary and other databases, using the key “breast cancer”, “local recurrence”, “intraoperative radiotherapy” and “radiation technique”, 45 were included in the literature review. Results. Radiotherapy is of paramount importance in the organpreserving treatment of breast cancer, as numerous randomised studies have shown that the use of postoperative radiotherapy dramatically reduces the number of locoregional recurrences. The use of IORT as an effective method of relapse prevention compared to standard postoperative adjuvant radiotherapy is an important trend in radiation oncology.Conclusion. The use of IORT in combination treatment modality for operable breast cancer should be differentiated and based on clinical and morphological prognostic factors. Different molecular subtypes of breast cancer are characterized by significant differences in pathogenesis and response to therapy. Further studies on the effectiveness of IORT are required to identify a group of patients with absolute indications for the use of IORT.

Combined modality treatment of patients with stage IV gastric cancer with peritoneal carcinomatosis

Peritoneal carcinomatosis is associated with poor prognosis in gastric cancer patients. Stage IV gastric cancer (GC) is diagnosed in 39.8 % of patients; local metastases without evidence of distant metastases occur only in 18–20 % of stage IV gastric cancer patients.The purpose of the study was to estimate the efficacy of personalized chemotherapy in the combined modality treatment of patients with stage IV GC with peritoneal carcinomatosis.Material and Methods. Cytoreductive surgery was performed in 70 patients with GC with peritoneal dissemination. The control group patients (n=35) received postoperative chemotherapy with the FOLFOX regimen. The study group patients (n=35) received personalized systemic and intraperitoneal chemotherapy based on the expression of chemosensitivity and resistance genes.Results. The median survival time (18.7 months) in the study group patients was higher than that in the control group and in studies described in the world literature (CRS + HIPEC). Personalized chemotherapy improved median progressionfree survival (PFS) by 4.6 months (29.1 %) and median overall survival (OS) by 6 months (32 %) compared to FOLFOX regimen chemotherapy. In the study group, the 1-, 2and 3-year survival rates were observed in 35 (100 %), 9 (27 %) and 1 (3 %) patients, respectively.Conclusion. Personalized chemotherapy in the combined modality treatment can improve long-term treatment outcomes (longer median PFS and OS) in GC patients with peritoneal dissemination.

A Multicenter Phase 2 Clinical Trial of 10-Day Decitabine, Dose-Escalated Donor Lymphocyte Infusion, and Ruxolitinib for Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndromes after Allogeneic Hematopoietic Cell Transplantation

Post-transplantation relapse of acute myeloid leukemia and myelodysplastic syndromes has a poor prognosis. Donor lymphocyte infusion (DLI) is one treatment approach. However, efficacy is limited, and toxicity, mostly in the form of acute graft-versus-host disease (GVHD), is frequent. We tested a novel approach using 10-day decitabine, dose-escalated DLI, and ruxolitinib in a multicenter phase 2 trial aimed at increasing the efficacy of DLI and reducing its toxicity. Up to four 28-day cycles were administered. The primary endpoint was 6-month overall survival (OS). Of the 14 patients who started cycle 1, 13 received 1 DLI, 6 received 2 DLIs, and 1 received 3 4 DLIs. A preplanned interim analysis after enrolling 14 patients suggested futility, and the trial was closed to accrual. The final analysis showed a 6-month OS of 36% (95% confidence interval [CI], 18 to 72), a 1-year progression-free survival of 7% (95% CI, 1% to 47%), a 6-month cumulative incidence of grade II-IV acute GVHD of 57% (95% CI, 26% to 80%), and a 1-year nonrelapse mortality of 14% (95% CI, 2% to 38%). The combined modality treatment studied in this trial was ineffective and did not reduce DLI toxicity.

Experimental study of EGFR-TKI aumolertinib combined with ionizing radiation in EGFR mutated NSCLC brain metastases tumor

Aumolertinib is an irreversible third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), although it has been administered for the treatment of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). However, it is unclear whether aumolertinib combined with ionizing radiation (IR) has potential therapeutic effects in treating brain metastases (BM) tumors from NSCLC. This study explored the anti-tumor effects of aumolertinib combined with IR in epidermal growth factor receptor mutated (EGFRm) NSCLC BM tumors. First, we established a xenograft model of NSCLC BM tumors in BALB/c nude mice and assessed the anti-tumor effects of this combination. Furthermore, we examined the concentrations of aumolertinib in brain tissue and blood using liquid chromatography-mass spectrometry (LC-MS); after that, we used CCK-8, colony formation, flow cytometry assay, and immunofluorescence staining to detect the effects of aumolertinib combined with IR upon PC-9 and NCI–H1975 cells, such as cell proliferation, survival, apoptosis, cycle distribution, the situation of DNA damage, and the expression levels of relevant proteins which were detected via western blotting; finally, we chose a clinical case with which to explore the clinical benefits to the EGFRm NSCLC BM patient after the treatment of the aforementioned combination. The experiments of NSCLC BM tumor animal models demonstrated that the combination enhanced the therapeutic effects and increased the intracranial accumulation of aumolertinib; the combination can inhibit cell proliferation and survival, delay the repair of DNA damage, and increase the rates of cell apoptosis and aumolertinib abrogated G2/M phase arrest, which the IR induced; the clinical study verified that the combination demonstrated better patient benefits. In conclusion, our study demonstrated that combining aumolertinib and IR has promising anti-tumor effects in EGFR-mutant NSCLC and that this combined treatment modality may be employed as a potential therapeutic strategy for EGFR-mutant NSCLC BM patients clinically.

Combined Modality Bladder-Sparing Therapy for Muscle-Invasive Bladder Cancer: How (Should) We Do It? A Narrative Review.

Organ-sparing combined-modality treatment for muscle-invasive bladder cancer remains underutilized despite high-quality evidence regarding its efficacy, safety, and preservation of quality of life. It may be offered to patients unwilling to undergo radical cystectomy, as well as those unfit for neoadjuvant chemotherapy and surgery. The treatment plan should be tailored to each patient's characteristics, with more intensive protocols offered to patients who are fit for surgery but opt for organ-sparing. After a thorough, debulking transurethral resection of the tumor and neoadjuvant chemotherapy, the response evaluation should trigger further management with either chemoradiation or early cystectomy in non-responders. A hypofractionated, continuous radiotherapy regimen of 55 Gy in 20 fractions with concurrent radiosensitizing chemotherapy with gemcitabine, cisplatin, or 5-fluorouracil and mitomycin C is currently preferred based on clinical trials. The response should be evaluated with repeated transurethral resections of the tumor bed and abdominopelvic-computed tomography after chemoradiation, with quarterly assessments during the first year. Salvage cystectomy should be offered to patients fit for surgery who failed to respond to treatment or developed a muscle-invasive recurrence. Non-muscle-invasive bladder recurrences and upper tract tumors should be treated in line with guidelines for respective primary tumors. Multiparametric magnetic resonance can be used for tumor staging and response monitoring, as it may distinguish disease recurrence from treatment-induced inflammation and fibrosis.

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.

Blood glucose control with different treatment regimens in type 2 diabetes patients hospitalized with COVID-19 infection: A retrospective study.

Coronavirus disease (COVID-19) is closely associated with hyperglycemia and a worse prognosis in patients with a previous diagnosis of type 2 diabetes mellitus. A few studies investigated the effects of diabetes treatment regimens in these patients during hospitalization. Here, we evaluate the impact of insulin and non-insulin therapy on glucose control in patients with type 2 diabetes admitted with COVID-19. This is a retrospective study including 359 COVID-19 patients with type 2 diabetes. Patients were divided into 2 groups according to diabetes treatment during hospitalization. The first group included patients treated with insulin only, and the second group patients treated with other antidiabetic agents with or without insulin. Average blood glucose was higher in the insulin-only treatment group (201 ± 66 mg/dL vs 180 ± 71 mg/dL, P = .004), even after excluding mechanically ventilated patients (192 ± 69 vs 169 ± 59 mg/dL, P = .003). In patients with moderate severity of COVID-19, average blood glucose was also significantly higher in the insulin-only treated group (197 ± 76 vs 168 ± 51 mg/dL, P = .001). Most patients (80%) in the combination treatment group received metformin. Moderately affected COVID-19 patients with type 2 diabetes could safely be treated with antihyperglycemic medications with or without insulin.

Moderators of the response to deep TMS for smoking addiction.

Deep repetitive transcranial magnetic stimulation (Deep TMS™) was recently cleared by the FDA as a short-term treatment for smoking cessation. However, it is unknown which participants are more likely to benefit from the treatment. We evaluated the data from the published randomized controlled trial of 262 participants 22-70 years old that led to the FDA clearance to characterize demographic and smoking history factors that moderate Deep TMS treatment efficacy. The current analysis included 75 completers in the active TMS group and 94 completers in the sham TMS group. We found that participants younger than 40 had four times the quit rate than those older than 40. Additionally, participants who quit following treatment smoked 10 years less than non-quitters. Moreover, Caucasian participants had two times the quit rate than African-American participants. Strikingly, participants with more than 12 years of education had 7 times the quit rate than participants with less education. Three weeks of Deep TMS has a higher smoking addiction quit rate in participants who are younger, more educated, Caucasian and with less extensive smoking history. Participants who are older, with less education and more extensive smoking history may need a longer treatment course and/or combined treatment modalities. Potential reasons may be related to the challenges of inducing neuronal modifications in those with greater physical and psychological dependence. Further investigation is warranted.

Non-Surgical management with Intra-Arterial Concurrent Chemo Radio Therapy (IACCRT) can be a definitive organ preservation treatment for buccal cancer patient

Conventional Head and Neck cancer treatment with primary surgical intervention is a relatively suffering manipulation because of causing severe facial deformity, and mastication malfunction, and resulted in a very poor quality of life for the patients afterward. And post-operation adjuvant therapy with combined modality treatment with Concurrent Chemo-Radio Therapy (CCRT) has been recommended approach for H&amp;N cancer for decades too. But it is also relatively more toxic to the patient, and further severely disrupts patients’ quality of life due to systemic side-effects caused by intravenous cytotoxic drug delivery. Intra-arterial infusion chemotherapy is another option for CCRT because of not only a better tumor response documented, and also bonus a better quality of life improvement. The demonstrated H&amp;N cancer patient approaching with Intra-Arterial Concurrent Chemo-Radio Therapy (IACCRT) showed a very satisfactory curative outcome. Besides the much better quality of life for the patient was conserved, it also bonuses to restore the patient’s dignity of life when compared to the conventional suffering surgical intervention. Such highly humanize IACCRT treatment modality for H&amp;N cancer patients should be recommended and encouraged in clinical practice.