Chemoradiotherapy Regimen Research Articles

Prise en charge des cancers bronchiques à petites cellules de stade localisé i actualisation

Limited-stage small cell lung cancer (LS-SCLC) represents 15-20 % of all lung cancers, and because of its rapid tumor kinetics, less than a third of SCLC are discovered at limited stage. The different steps and modalities of its management are well defined and codified. They involve a comprehensive staging assessment using CT scans of the chest, abdomen, and pelvis, PET-CT scans, and ideally brain imaging using MRI to avoid missing a more extensive stage of the disease, which would significantly alter the treatment strategy. The treatment consists of a combination of chemotherapy with platinum/ etoposide and radiotherapy, possibly delivered in a hyperfractionated schedule with two daily sessions. SCLC is particularly both chemosensitive and radiosensitive, so that the initial evaluation shows frequently a complete response, and prophylactic cranial irradiation (PCI) is then recommended. Relapses are unfortunately frequent, less responsive to second line treatments, and therapeutic options are limited. No targeted agents or immunotherapy have robustly demonstrated efficacy in the treatment of LSSCLC. Even if hyperfractionated accelerated radiotherapy (HFART) at the dose of 45Gy in 30 fractions has given the best results, most clinicians use once-daily chemoradiation regimen (60-70Gy). Studies have evaluated dose escalation either with HFRAT or with conventional fractionation (66 to 70Gy). Several trials are currently investigating the addition of immunotherapy to chemoradiation, hippocampus sparing PCI or the omission of PCI. In rare cases of very early-stage SCLC, surgery or stereotactic radiotherapy may be envisaged.1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Management of patients with reduced dihydropyrimidine dehydrogenase activity receiving combined 5-fluoruracil-/capecitabine-based chemoradiotherapy.

5‑Fluoruracil (5-FU) and its oral prodrug capecitabine are mainstays in combined chemoradiotherapy regimens. They are metabolized by dihydropyrimidine dehydrogenase (DPYD). Pathogenic variants of the DPYD gene cause areduction in DPYD activity, leading to possibly severe toxicities. Therefore, patients receiving 5‑FU-/capecitabine-based chemoradiotherapy should be tested for DPYD variants. However, there are limited clinical data on treatment adjustments and tolerability in patients with decreased DPYP activity receiving combined chemoradiotherapy. Therefore, aretrospective analysis of the toxicity profiles of patients with decreased DPYD activity treated at our center was conducted. For all patients receiving 5‑FU-/capecitabine-based chemo(radio)therapy at our department, DPYD activity was routinely tested. Genotyping of four DPYD variants (DPYD*2A, DPYD*13, c.2846A > T, and haplotype B3) was conducted according to the recommendation of the German Society for Hematooncology (DGHO) using TaqMan hydrolysis polymerase chain reaction (PCR; QuantStudy3, Thermo FisherScientific, Darmstadt). DPYD variants and activity score as well as clinical data (tumor entity, treatment protocol, dose adjustments, and toxicity according to the Common Terminology Criteria for Adverse Events [CTCAE]) were assessed and reported. Of 261 tested patients, 21exhibited DPYD variants, 18of whom received chemoradiotherapy. All but one patient was treated for rectal or anal carcinoma. The observed rate of DPYD variants was 8.0%, and heterozygous haplotype B3 was the most common (5.75%). One patient exhibited ahomozygous DPYD variant. DPYD activity score was at least 0.5in heterozygous patients; chemotherapy dose was adjusted accordingly, with an applied dose of 50-75%. CTCAE grade2 skin toxicity (50%) and grade3 leukopenia (33.3%) were most common. One patient experienced atransient grade4 increase in transaminases. All high-grade toxicities were manageable with supportive treatment and transient. No CTCAE grade5 toxicities related to 5‑FU administration were observed. With dose reduction in heterozygous patients, toxicity was within the range of patients without DPYD variants. Our clinical data suggest that dose-adapted 5‑FU-/capecitabine-chemoradiotherapy regimens can be safely considered in patients with heterozygous clinically relevant DPYD variants, but that the optimal dosage still needs to be determined to avoid both increased toxicity and undertreatment in acurative setting.

LBA81 Durvalumab (D) as consolidation therapy in limited-stage SCLC (LS-SCLC): Outcomes by prior concurrent chemoradiotherapy (cCRT) regimen and prophylactic cranial irradiation (PCI) use in the ADRIATIC trial

LBA81 Durvalumab (D) as consolidation therapy in limited-stage SCLC (LS-SCLC): Outcomes by prior concurrent chemoradiotherapy (cCRT) regimen and prophylactic cranial irradiation (PCI) use in the ADRIATIC trial

Utility of SATB2 and MOC-31 Immunostains to Distinguish Between Poorly Differentiated Rectal Adenocarcinoma and Anal Squamous Cell Carcinoma.

Colorectal adenocarcinoma and squamous cell carcinoma (SCC) can arise in the anorectum and present a significant diagnostic challenge when poorly differentiated. Accurate diagnosis can significantly influence management, as the treatments for these conditions involve distinct neoadjuvant chemoradiotherapy regimens. MOC-31 and SATB2 have been utilized as specific markers of glandular differentiation and colorectal origin, respectively, but studies have shown that they may be positive in squamous cell carcinoma of other sites. This raises the concern that MOC-31 and SATB2 may be positive in squamous cell carcinoma of the anorectum, and overreliance on these stains may be a potential diagnostic pitfall in differentiating rectal poorly differentiated adenocarcinoma (PDA) from anal nonkeratinizing SCC. We identified biopsies from 10 rectal PDA and 17 anorectal nonkeratinizing SCC cases and stained them for MOC-31 and SATB2. We found that MOC-31 was highly sensitive, being positive in 10/10 cases of rectal PDA, but not specific, as it was also positive in 11/17 SCC cases. In contrast, SATB2 was both sensitive, with positive staining in 10/10 rectal PDA cases, and specific, with negative staining in 17/17 SCC cases. This includes equivocal staining in 4 of these negative SCC cases. MOC-31 had a sensitivity of 100% and specificity of 35.3%, while SATB2 had a sensitivity of 100% and specificity of 100%. Unlike squamous mucosa of the head and neck, and esophagus, SCC of the anus does not frequently stain positively for SATB2. These data suggest that SATB2 is a reliable marker in distinguishing rectal PDA from anorectal nonkeratinizing SCC, whereas MOC-31 is commonly positive in SCC of the anus. It is also important to note that equivocal SATB2 staining may be seen in SCC.

Conversion chemoradiotherapy combined with nab-paclitaxel plus cisplatin in patients with locally advanced borderline-resectable or unresectable esophageal squamous cell carcinoma: a phasei/ii prospective cohort study.

To evaluate the efficacy and safety of nab-paclitaxel plus cisplatin as the regimen of conversional chemoradiotherapy (cCRT) in locally advanced borderline resectable or unresectable esophageal squamous cell carcinoma (ESCC). Patients with locally advanced ESCC (cT3‑4, Nany, M0‑1, M1 was limited to lymph node metastasis in the supraclavicular area) were enrolled. All the patients received the cCRT of nab-paclitaxel plus cisplatin. After the cCRT, those resectable patients received esophagectomy; those unresectable patients continued to receive the definitive chemoradiotherapy (dCRT). The locoregional control (LRC), overall survival (OS), event-free survival (EFS), distant metastasis free survival (DMFS), pathological complete response (pCR), R0resection rate, adverse events (AEs) and postoperative complications were calculated. 45patients with ESCC treated from October 2019 to May 2021 were finally included. The median follow-up time was 30.3 months. The LRC, OS, EFS, DMFS at 1and 2years were 81.5%, 86.6%, 64.3%, 73.2 and 72.4%, 68.8%, 44.8%, 52.7% respectively. 21patients (46.7%) received conversional chemoradiotherapy plus surgery (cCRT+S). The pCR rate and R0resection rate were 47.6 and 84.0%. The LRC rate at 1and 2years were 95.0%, 87.1% in cCRT+Spatitents and 69.3%, 58.7% in dCRT patients respectively (HR, 5.14; 95%CI, 1.10-23.94; P = 0.021). The toxicities during chemoradiotherapy were tolerated, and the most common grade3-4 toxicitiy was radiation esophagitis (15.6%). The most common postoperative complication was pleural effusion (38.1%) and no grade ≥ IIIb complications were observed. nab-paclitaxel plus cisplatin are safe as the regimen of conversional chemoradiotherapy of ESCC.

Intensive pediatric chemotherapy regimen (PNET HR+5) in adult high-risk medulloblastoma and pinealoblastoma patients

Abstract Background High-risk medulloblastoma (HRMB) is rare in adults. The 5-year overall survival rate is less than 60%. We present here a retrospective analysis of adults treated with an intensive pediatric chemo-radiotherapy regimen PNET HR+5: NCT00936156. Methods 18 patients over the age of 20 (range, 20-33 years) with HRMB (n = 13), pinealoblastoma (n = 4) and central nervous system embryonal tumor (n = 1) were treated with 2 courses of carboplatin-etoposide followed by 2 courses of high-dose thiotepa (HDT) with autologous hematopoietic stem-cell rescue. A craniospinal irradiation (CSI) (36 Gy craniospinal axis then a boost of 18 Gy to the primary tumor site) was then initiated within 150 days of surgery, completed with 6 cycles of temozolomide; the axis irradiation was not mandatory for non-metastatic pinealoblastoma. Results We observed no progression under chemotherapy and no toxic death. Four patients received only 1 HDT. Two non-metastatic pinealoblastoma received only focal irradiation. One medulloblastoma received only 25 Gy on axis. 56% (10/18) received 6 cycles of temozolomide. No long-term toxicity was recorded. Median time between surgery and CSI was 175 days (range, 115-250). With a median follow-up of 6.0 years (range, 2.6-9), the progression-free survival and overall survival rates for medulloblastoma were respectively 65% (95% CI: 31-86%) and 76% (95% CI: 42-91%) at 5 years. Conclusions The PNET HR+5 regimen showed promising results in an adult population, with a meaningful improvement in progression-free survival and overall survival in patients with HRMB.

Comparison of the treatment outcomes of different neoadjuvant chemoradiotherapy regimens for resectable locally advanced esophageal cancer

BackgroundNeoadjuvant chemoradiotherapy (nCRT) followed by radical esophagectomy is the standard treatment for locally advanced esophageal squamous cell cancer (LA-ESCC). However, various nCRT regimens have been used, and their comparative efficacy and safety remain unclear. MethodsPatients with histologically confirmed LA-ESCC who underwent nCRT followed by radical esophagectomy between January 2016 and February 2022 were enrolled in this study. Of note, 3 different nCRT regimens were retrospectively compared: conventional radiotherapy (RT) + cisplatin/5-fluorouracil (FP) (Conv-FP), hypofractionated RT + FP (Hypo-FP), and regimens from the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial (CROSS). The overall survival (OS), pathologic complete response (pCR), toxicity, and treatment compliance rates were analyzed. ResultsAmong the 600 patients, 225 received Conv-FP, 255 received Hypo-FP, and 120 received the CROSS regimen. The OS rates at 1 year were 78.7%, 83.9%, and 88.1% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (P < .001). The pCR rates were 30.6%, 33.9%, and 35.0%, respectively (P = .653). The overall incidence of grade 3 toxicities was 10.2%. Hematologic and nonhematologic toxicities of grade ≥ 3 were observed in 8.4% and 11.4%, 0% and 7.6%, and 5.5% and 0.8% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (P = .002 and P = .030). Weight loss of > 5% was observed in 44.0%, 51.4%, and 32.5% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (P < .001). In the multivariate analysis, clinical T stage (P = .004), N stage (P = .012), FP chemotherapy regimen (P = .013), surgical resection (P < .001), hematologic toxicity (P = .001), and weight loss (P = .004) were significantly associated with poor OS. ConclusionThe choice of nCRT regimen did not significantly affect the pCR rates in patients with LA-ESCC. However, the CROSS regimen demonstrated better OS and lower toxicity, suggesting that it may be the optimal treatment option among the groups.

Long-Term Results of Bladder Preservation With Twice-Daily Radiation Plus 5-Fluorouracil/Cisplatin or Daily Radiation Plus Gemcitabine for Muscle-Invasive Bladder Cancer—Updated Report of NRG/RTOG 0712: A Randomized Phase 2 Trial

Purpose5-FU/cisplatin and twice-daily radiation (FCT) or gemcitabine and once daily radiation (GD) are effective chemoradiation (CRT) regimens for bladder sparing treatment of muscle-invasive bladder cancer (MIBC). This trial evaluated these regimens and demonstrated efficacy with either regimen at 3 years. With further follow-up, longer term results are reported here. Methods and MaterialsPatients with cT2-4a MIBC were randomized to FCT or GD. Patients had a transurethral resection and induction CRT to 40 Gy. Patients with a complete response (CR) received consolidation CRT to 64 Gy. Others had cystectomy. Adjuvant gemcitabine/cisplatin chemotherapy was administered. The primary endpoint was freedom from distant metastasis (FDM). This updated analysis reports 7-year data. Toxicity and efficacy endpoints, including bladder intact distant metastasis free survival (BI-DMFS) were also assessed. ResultsFrom 12/2008 to 4/2014, 70 patients were enrolled; 66 eligible for analysis, 33 per arm. Median follow-up was 9.1 years for eligible living patients. At 7 years, FDM was 65% and 73% for FCT and GD, respectively. BI-DMFS was 58% (95% CI: 41 – 76) and 68% (95% CI: 51-84), respectively. The post-hoc hazard ratio of 0.75 (95% CI: 0.37-1.55) showed no difference between treatments (p=0.44). Overall survival at 7 years was 48% and 59%. There were 4 and 5 cystectomies performed for FCT and GD, respectively. In the FCT arm, there were 5 (16%), 1 (3%) and 0 grade 3, 4 and 5 late toxicities reported. In the GD arm, there were 7 (23%), 0 and 0. ConclusionsBoth regimens maintained high FDM rates at 7 years. Cystectomy rates were low and overall survival rates high on both arms. Late toxicity rates were low. Either gemcitabine and daily radiation or a cisplatin-based regimen are effective bladder sparing therapies.

Treatment Outcomes in Primary Mediastinal Large B-Cell Lymphoma. Experience of the AF Tsyb Medical Radiological Research Center (Obninsk)

AIM. To assess chemotherapy outcomes in patients with primary mediastinal large B-cell lymphoma (PMBCL) treated at the AF Tsyb Medical Radiological Research Center from 2016 to 2023. MATERIALS &amp; METHODS. The analysis focused on the data from 58 patients with the morphologically verified diagnosis of PMBCL. The patients were aged 17–62 years (median 34 years), there were 39 women and 19 men. The median follow-up was 51.2 months (range 0.4–200.9 months). Depending on drug chemotherapy regimens, patients were divided into 3 groups: R-NHL-BFM-90 (n = 9), R-CHOP (n = 17), and R-MACOP-B (n = 32). Most patients (90 %) received mediastinal radiotherapy of total 30–46 Gy. RESULTS. The 5-year overall survival in the therapy groups was 66.7 %, 88.2 %, and 100 %, respectively (p = 0.007), progression-free survival was 66.7 %, 70.6 %, and 96.9 % (p = 0.006), and event-free survival was 66.7 %, 54.7 %, and 90.6 % (p = 0.038). On the whole, the toxicity profile of chemotherapy was quite acceptable. Neither low blood values nor other adverse events essentially affected a complete implementation of chemoradiotherapy program. The intermediate outcomes were based on PET-CT data after 2–4 therapy cycles in 37 (64 %) patients. PET-CT showed that at the stage of drug chemotherapy, complete response (CR) was achieved in 27 (73 %) patients, and partial response (PR) was achieved in 4 (11 %) patients. With respect to the CR and PR criteria, there were 6 (16 %) non-responders. CONCLUSION. PMBCL is one of extranodal lymphomas with thymic B-cells being primary source of tumor growth. PMBCL is characterized by aggressive course and extreme heterogeneity of clinical manifestations. Up to now, the first-line chemotherapy decision making in PMBCL has remained an issue with practical importance. This paper reports immediate and long-term outcomes of the program chemoradiotherapy regimen R-MACOP-B with subsequent consolidation radiotherapy. The results obtained can be termed quite satisfactory and noninferior to the data from national and international sources. Nevertheless, more effective chemoradiotherapy programs for PMBCL continue to be elaborated. In this context, immune checkpoint inhibitors as part of therapy programs seem to hold promise for the treatment of newly diagnosed PMBCL.

Tumor recurrence and survival prognosis in patients with advanced gastric cancer after radical resection with radiotherapy and chemotherapy.

Advanced gastric cancer is a common malignancy that is often diagnosed at an advanced stage and is still at risk of recurrence after radical surgical treatment. Chemoradiotherapy, as one of the important treatment methods for gastric cancer, is of great significance for improving the survival rate of patients. However, the tumor recurrence and survival prognosis of gastric cancer patients after radiotherapy and chemotherapy are still uncertain. To analyze the tumor recurrence after radical radiotherapy and chemotherapy for advanced gastric cancer and provide more in-depth guidance for clinicians. A retrospective analysis was performed on 171 patients with gastric cancer who received postoperative adjuvant radiotherapy and chemotherapy in our hospital from 2021 to 2023. The Kaplan-Meier method was used to calculate the recurrence rate and survival rate; the log-rank method was used to analyze the single-factor prognosis; and the Cox model was used to analyze the prognosis associated with multiple factors. The median follow-up time of the whole group was 63 months, and the follow-up rate was 93.6%. Stage II and III patients accounted for 31.0% and 66.7%, respectively. The incidences of Grade 3 and above acute gastrointestinal reactions and hematological adverse reactions were 8.8% and 9.9%, respectively. A total of 166 patients completed the entire chemoradiotherapy regimen, during which no adverse reaction-related deaths occurred. In terms of the recurrence pattern, 17 patients had local recurrence, 29 patients had distant metastasis, and 12 patients had peritoneal implantation metastasis. The 1-year, 3-year, and 5-year overall survival (OS) rates were 83.7%, 66.3%, and 60.0%, respectively. The 1-year, 3-year, and 5-year disease-free survival rates were 75.5%, 62.7%, and 56.5%, respectively. Multivariate analysis revealed that T stage, peripheral nerve invasion, and the lymph node metastasis rate (LNR) were independent prognostic factors for OS. Postoperative intensity-modulated radiotherapy combined with chemotherapy for gastric cancer treatment is well tolerated and has acceptable adverse effects, which is beneficial for local tumor control and can improve the long-term survival of patients. The LNR was an independent prognostic factor for OS. For patients with a high risk of local recurrence, postoperative adjuvant chemoradiation should be considered.

Incidence and outcomes of atrial fibrillation in different cancer subtypes: A propensity-matched analysis of Nationwide Readmissions Database.

e23324 Background: Significant concern exists over the cardiotoxic effects of chemo &amp; radiation therapy used in the management of cancer patients. With different cancers requiring different chemo-radiotherapy regimens, cardiotoxicity risk is quite variable. We aim to evaluate the rates of atrial fibrillation (AF) in various cancers. Methods: The national readmission database (2016-2020) was queried to identify all-cause admissions for patients with active malignancy of any origin. The study population was divided into six subgroups based on the type of cancer (colorectal, renal, lung, breast, prostate, and hematological). Multivariate regression analysis was utilized for adjusted odds of mortality. A propensity score matching (PSM) model matched malignancy of interest with other malignancies to obtain incidence rates. Results: Among 10.6 million all-cause cancer-related hospitalizations, about 1.5 million (14%) developed atrial fibrillation (AF). On propensity-matched cohorts, AF had its highest incidence in hospitalizations associated with hematological malignancies (17%), followed by prostate (16.5%), lung (15.9%), renal (12.5%), colorectal (11.5%) &amp; breast (10.5%) malignancies [p &lt; 0.05]. Moreover, cancer hospitalizations complicated by AF were associated with higher mortality. AF was associated with the highest odds of mortality in breast cancer (aOR:1.60), followed by colorectal (aOR:1.59), hematological (aOR:1.55), prostrate (aOR:1.52), renal (aOR:1.51) &amp; lung (aOR:1.51) malignancies [p &lt; 0.001]. The rates of 30-day AF-related readmission were highest in hematological malignancies (21%), followed by lung (18.8%), colorectal (17.1%), breast (16.1%), prostate (15.7%) &amp; renal (12.5%) malignancies [p &lt; 0.05]. Conclusions: The rate of AF in nationwide hospitalizations among cancer patients was ~ 14%. AF was found to have the highest incidence &amp; readmission in hematological malignancies, while AF-related mortality was highest among breast cancer.

Sequential chemoradiotherapy versus induction chemotherapy plus concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: A multicentre, open-label, non-inferiority, randomised, phase 3 trial.

6075 Background: Induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) has been regarded as standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) due to its favorable disease control. Now, distant metastasis was the main cause of failure. However, concurrent cisplatin is associated with intolerable toxicities and ineffective in preventing distant metastasis. Since IMRT enhances the local control and chemotherapy before or after radiotherapy decreases the risk of distant failure, it is worth exploring whether sequential chemoradiotherapy (SCRT) regimen could replace IC+CCRT for patients with LA-NPC. Methods: This open-label, phase 3, non-inferiority clinical trial was conducted from January 2018 to September 2021 in 6 centers in China. Patients aged 18–65 years with stage T1-4N2-3 or T3-4N0-1 M0 NPC were randomly assigned (1:1) to receive 2 cycles of IC with GP regimen (gemcitabine 1000mg/m2 d1,8 + cisplatin 25 mg/m2 d1-3, q21d) plus IMRT, followed by 2 cycles of adjuvant chemotherapy (AC) with the same regimen or IC with GP regimen for 2 cycles followed by IMRT plus concomitant weekly cisplatin (30 mg/m²). The primary endpoint was 3-year failure-free survival (FFS) with non-inferiority margin of 10% (HR&lt;1.6) and the incidence of grade ≥3 acute mucositis during radiotherapy. Efficacy analysis and safety analysis were dividedly performed in the intention-to-treat and safety population. Results: A total of 420 patients were randomly assigned to SCRT group (n = 210) or IC+CCRT group (n = 210). With a median follow-up of 47.0 months (IQR: 35.0-57.8), the 3-year FFS was 84.0% in SCRT group versus 79.8% in IC+CCRT group (log rank P=0.344), with an HR of 0.804 (95% CI, 0.510 to 1.266) and absolute difference of 4.2% (95% CI, -3.2 to 11.6). No significant differences were observed between groups in 3-year overall survival (97.4% vs. 94.5%; HR 0.413; 95% CI, 0.159 to 1.076; log rank P=0.061), locoregional control (91.7% vs. 88.8%; HR 0.767; 95% CI, 0.420 to 1.401; log rank P=0.386), or distant metastasis-free survival (93.6% vs. 91.5%; HR 0.756; 95% CI, 0.376 to 1.520; log rank P=0.430). Compared with IC+CCRT group, the SCRT group had significantly lower incidences of grade ≥3 acute nonhematological AEs due to the omission of concurrent chemotherapy (including acute mucositis 29.0% vs. 41.9%, P&lt;0.001; nausea 9.5% vs. 18.1%, P=0.011; and vomiting 3.8% vs. 9.5%, P=0.019), and higher incidences of grade ≥3 acute hematological AEs (including thrombocytopenia and leukopenia) due to the additional AC. Conclusions: For LA-NPC, SCRT was not inferior in 3-year FFS to IC+CCRT. It might be an alternative treatment for LA-NPC patients with fewer sever nonhematological AEs during IMRT. Clinical trial information: NCT03366415 .

Tumor treating fields for newly diagnosed high-grade glioma based on the criteria of 2021 WHO CNS5: A retrospective analysis of Chinese patients in a single center.

High-grade glioma (HGG) is known to be characterized by a high degree of malignancy and a worse prognosis. The classical treatment is safe resection supplemented by radiotherapy and chemotherapy. Tumor treating fields (TTFields), an emerging physiotherapeutic modality that targets malignant solid tumors using medium-frequency, low-intensity, alternating electric fields to interfere with cell division, have been used for the treatment of new diagnosis of glioblastoma, however, their administration in HGG requires further clinical evidence. The efficacy and safety of TTFields in Chinese patients with HGG were retrospectively evaluated by us in a single center. We enrolled and analyzed 52 patients with newly diagnosed HGG undergoing surgery and standard chemoradiotherapy regimens from December 2019 to June 2022, and followed them until June 2023. Based on whether they used TTFields, they were divided into a TTFields group and a non-TTFields group. Progression-free survival (PFS) and overall survival (OS) were compared between the two groups. There were 26 cases in the TTFields group and 26 cases in the non-TTFields group. In the TTFields group, the median PFS was 14.2 months (95% CI: 9.50-18.90), the median OS was 19.7 months (95% CI: 14.95-24.25) , the median interval from surgery to the start of treatment with TTFields was 2.47 months (95% CI: 1.47-4.13), and the median duration of treatment with TTFields was 10.6 months (95% CI: 9.57-11.63). 15 (57.69%) patients experienced an adverse event and no serious adverse event was reported. In the non-TTFields group, the median PFS was 9.57 months (95% CI: 6.23-12.91) and the median OS was 16.07 months (95% CI: 12.90-19.24). There was a statistically significant difference in PFS (p = 0.005) and OS (p = 0.007) between the two groups. In this retrospective analysis, TTFields were observed to improve newly diagnosed HGG patients' median PFS and OS. Compliance was much higher than reported in clinical trials and safety remained good.

Cisplatin and capecitabine as definitive chemoradiation for squamous cell carcinoma of the anal canal (SCCAC): A prospective cohort.

e15503 Background: SCCAC is a rare disease. The standard of care treatment with curative intent is chemoradiation (CRT) with mitomycin (MMC) or cisplatin (CDDP) plus infusional 5-Fluoracil (5-FU). Capecitabine may replace 5-FU in MMC doublet. However, MMC and infusional pumps are frequently unavailable in underdeveloped countries. CCDP and capecitabine are widely available, but there is no prospective data about the feasibility and efficacy of this combination in a definitive SCCAC CRT setting. Methods: A Prospective cohort study aimed to evaluate the safety and efficacy of treatment with chemoradiation with CDDP 60mg/m2 D1 and D29 plus Capecitabine 825mg/m2 BID in a population without MMC and infusional pump access. Eligible patients (pts) had T2-4, N0-3, and M0 disease candidates for a full curative CRT regimen. The study data were prospectively collected using REDCap. The primary endpoint was the response by RECIST v.1.1 at 24 weeks(w). The secondary endpoints included toxicity by CTCAE v.5.0, adherence, PFS, and OS. Results: We enrolled 40 consecutive pts between Aug/2019-Dec/2022 in a tertiary cancer center in Brazil. The median age was 61y, the majority were stage III (n = 31, 77.5%) and ECOG 1 (n = 20, 50%). HIV+ serology was observed in 11 pts (27,5%). All patients received CRT, with a median dose of 54Gy in the primary tumor and 45Gy in the elective nodes. At 8w, 35% (n = 14) had a complete response (CR), 50% (n = 20) partial response (PR), and 2.5% (n = 1) progressive disease (PD). At 6 months, CR was observed in 55% (n = 22), PR in 22.5% (n = 9), and PD in 10% (n = 4). 11 pts had disease recurrence, and six died. 1y OS was 94.7% (IC95%: 80.7- 98.6%), and 1y PFS was 75.3% (IC95%:57.8 - 86.3%). Colostomy-free survival at one year was 89.6% (IC95%: 74.7 - 95.9%). Median PFS and OS were not reached with a 2-year median follow-up. Regarding toxicities, radiodermatitis was observed in 94% (n = 36), nausea in 90% (n = 36), and diarrhea in 65% (n = 26). Any grade 3/4 toxicity was present in 27.5% (n = 11), being the majority of radiodermatitis. Four older pts (average age 73y) had definitive suspension of treatment due to toxicity, 06 pts were hospitalized because of a skin infection, and one died due to treatment toxicity. Conclusions: Definitive chemoradiotherapy with cisplatin and capecitabine is feasible; however, older populations require extra attention to early toxicities management.

Salvage lung resection after immunotherapy is feasible and safe

ObjectivesPatients with non–small cell lung cancer treated with immunotherapy and modern chemoradiation regimens show improved progression-free and overall survival. However, patients with limited oligo-progression represent a potential population in which local therapy such as surgery may have a potential role as salvage treatment. The objectives of our study were to evaluate the feasibility and safety of salvage lung resection after immunotherapy in patients with non–small cell lung cancer. MethodsThe National Cancer Database was queried for patients diagnosed and treated for non–small cell lung cancer stage I to IV, from 2013 to 2020. Patients who underwent surgery as salvage after immunotherapy were defined as undergoing surgery >5 months from the initiation of immunotherapy. As a sensitivity analysis, patients who underwent surgery as salvage after chemoradiation were also analyzed in a similar fashion. Surgical outcomes such as type of surgery, complete resection (R0) rates, and complete pathologic response rates were determined for feasibility. Length of stay, 30-day readmission rates, and 30-day mortality rates were determined and overall survivals were estimated with Kaplan-Meier analysis to evaluate for safety. ResultsOf the 934,093 patients diagnosed with non–small cell lung cancer stage I to IV from 2013 to 2020, 164 patients received immunotherapy and after 5 months underwent surgery. Lobectomy was the most commonly performed operation (74%) and pneumonectomy was required in 9% (n = 15). R0 resection was achieved in 89% (n = 146) and of these patients, 23% (n = 37) had complete pathologic response. Median length of stay was 4 days, 30-day readmission was 5%, and 30-day mortality was 0.6%. In our sensitivity analysis of chemoradiation patients (n = 445), the above data were similar to previously reported cohort studies of patients undergoing chemoradiation and subsequently salvage surgery. ConclusionsLung resection after immunotherapy appears to be a feasible salvage treatment option, with lobectomy being most common and with high R0 resection rates. Low patient morbidity and mortality rates also suggest the safety of this approach. Salvage surgery may be considered in patients who have oligo-progression after immunotherapy within the context of a comprehensive multidisciplinary treatment plan.

Adjuvant Concurrent Chemoradiotherapy (CRT) plus Docetaxel-Cisplatin-Fluorouracil (DCF) versus CRT plus Fluorouracil-Folinic Acid (FUFA) in Stage III Gastric Cancer.

Adjuvant chemoradiotherapy (CRT) is the optimal management strategy in resectable gastric cancer. There is a debate about the efficacy of more aggressive CRT plus chemotherapy regimens in adjuvant setting. This study aimed to compare the efficacy of adjuvant CRT plus docetaxel-cisplatin-fluorouracil (DCF) versus CRT plus fluorouracil-folinic acid (FUFA) in stage III gastric cancer. Patients with a diagnosis of stage III gastric cancer treated with adjuvant therapy after curative resection were analyzed. Patients' disease characteristics and impacts of the regimens on median disease-free survival (DFS) and median overall survival (OS) were analyzed retrospectively. One hundred sixty-one patients (102 in FUFA arm and 59 in DCF arm) with a median age of 56.0 (29-79) were evaluated. In the DCF arm, there were more renal toxicities (31.6% vs 6.4% P < 0.001), emergency department admissions (64.9% vs 23.7%, P < 0.001), and dose reductions/treatment modifications in the DCF arm (51.6% vs 37.2, P < 0.001). The median follow-up was 23 months (1-124) in the FUFA arm and 26.0 months (1-77) in the DCF arm. The median DFS was 25.0 months (%95 CI, 12.7-37.2) in the DCF arm and 17.0 months (%95 CI, 2.6-31.3) in the FUFA arm, P = 0.66. The median OS was 28.0 months (%95 CI, 17.0-38.9) in the DCF arm and 25.0 months (%95 CI, 11.9-36.0) in the FUFA arm, P = 0.70. In conclusion, when compared with FUFA regimen, more aggressive therapy with DCF was more toxic and did not improve OS in adjuvant setting of stage III gastric cancer.

Prediction of radiation complications by determining the blood oxidation processes in cervical cancer patients under chemoradiotherapy

Background. Radiotherapy (RT) is one of the principal methods in cancer management, and its administration in oncology practice is much wider nowadays because of the increased incidence of newly diagnosed cancer cases with wide spread and aggressive course of tumor process, and also in view of organ-sparing strategies in the combined treatment. However, the radiation reactions, especially local ones in rectum or bladder, can’t be completely avoided even using the most advanced radiotherapy facilities and dosimetry planning. Therefore, at present time not only technical modernization, but also the progress in radiobiology should be considered. Given the cytotoxic properties of some anticancer drugs, they are used in the combined therapy of cervical cancer (CC) to receive a radiosensitizing effect on the malignant cells. In particular, cisplatin inhibits reparative processes by affecting the enzymes involved in restoring the integrity of DNA or chromosome structure. Administration of the combined radiation and chemotherapy leads not only to an increase in the percentage of tumor regression, but also to an increase in the number of radiation injuries to healthy tissues. Therefore, prediction of such injuries, research and development of means of their prevention and treatment in the regimen of chemoradiotherapy (ChRT) of CC is extremely urgent and remains an unsolved problem to date. Purpose. Development of personalized approaches in ChRT in CC patients by studying its efficiency, assessing its toxicity, and predicting radiation injuries according to the data of blood oxidative processes in patients. Materials and methods. The combined radiotherapy (CRT) and ChRT were administered to the stage IIB–IIIB CC (T2b-3bN0-1M0) patients (n = 105) at the National Cancer Institute. Patients aged 25–75 years were divided into two groups: the study group and the comparison group. Complex clinical examination was conducted prior to treatment featuring the assay of tumor parameters, state of «critical organs». At the stage I of CRT regimen, conformal irradiation on pelvis minor was delivered at the electron linear accelerator «Clinac 2100 CD» with an energy of 6 MeV per area of pelvis minor with single radiation dose (SRD) of 2.0 Gy and total radiation dose (TRD) of up to 46 Gy. Patients in the study group received the CRT along with administration of chemoradiomodifying agent cisplatin 40 mg/m2 once a week intravenously (drip-feed), patients in the comparison group received no radiomodifier. At the stage II of CRT regimen, an intracavitary brachytherapy (ICBT) was administered to the CC patients at the gamma therapy equipment «AGAT-VU» using 60Co (high dose rate – HDR) sources in the mode of SRD of 5 Gy 2 times a week, 7–8 fractions, and TRD of 35–40 Gy at p. A. The TRD in total was 77–89 Gy at the p. A and 54–60 Gy at p. B. Administration of cisplatin 40 mg/m2 at the stage II of CRT was continued in the study group once a week intravenously (drip-feed), total dose of up to 200–300 mg. Radiobiological studies were performed on the peripheral blood samples from the CC patients (n = 39) before and after ChRT. The control group consisted of healthy women of the appropriate age. Blood was sampled into the special 6 ml Vacutainer type tubes with an anticoagulant according to the manufacturer’s instructions (BioReagent). Intensity of generation of О• 2– in PBL was evaluated by the chemiluminescence method using the lucigenin indicator, which, as a result of reacting with О• 2–, emits light quanta recorded by the device. Measurements were carried out on the AutoLumat LB 953 device (Germany) with appropriate corrections made to the methodology. Results and discussion. Effectiveness of CRT in CC patients was evaluated according to regression of the primary tumor focus (clinical, ultrasound, MRI or SCT data) and presence/absence of toxic manifestations of treatment following the criteria for evaluating the solid tumors regression according to the Response Evaluation Criteria in Solid Tumor (RECIST). Conclusions. The results of the study indicate that chemoradiotherapy contributes to pronounced regression of cervical tumors and does not increase toxicity of treatment due to timely correction of complications.

Comparing upfront surgery with neoadjuvant treatments in patients with resectable, borderline resectable or locally advanced pancreatic cancer: a systematic review and network meta-analysis of randomized clinical trials

Background: To explore the optimal neoadjuvant therapy strategy for resectable, borderline resectable, and locally advanced pancreatic cancer, in order to provide a theoretical basis for the development of new neoadjuvant treatment protocols for clinical use. Patients and methods: We reviewed literature titles and abstracts comparing three treatment strategies (neoadjuvant chemoradiotherapy, neoadjuvant chemotherapy, and upfront surgery) in PubMed、Embase、The Cochrane Library、Web of Science from 2009 to 2023 to estimate relative odds ratios (ORs) for resection rate and hazard ratios (HR) for overall survival (OS) in all include trials. Results: A total of 9 studies involving 889 patients were included in the analysis. The treatment methods included upfront surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy followed by surgery. The network meta-analysis results demonstrated that neoadjuvant chemoradiotherapy followed by surgery was an effective approach in improving OS for resectable and borderline resectable pancreatic cancer patients compared to upfront surgery (HR: 0.79, 95% CI: 0.64-0.98) and neoadjuvant chemotherapy (HR: 0.79, 95% CI: 0.64-0.98). Additionally, neoadjuvant chemoradiotherapy significantly increased the margin negative resection (R0) rate and pathological negative lymph node (pN0) rate in patients with resectable and borderline resectable pancreatic cancer. However, it is worth noting that neoadjuvant chemoradiotherapy increased the risk of grade 3 or higher treatment-related adverse events, including in patients with locally advanced pancreatic cancer. Conclusions: The current evidence suggests that neoadjuvant chemoradiotherapy followed by surgery is the optimal choice for treating patients with resectable and borderline resectable pancreatic cancer. Future research should focus on optimizing neoadjuvant chemoradiotherapy regimens to effectively improve OS while reducing the occurrence of adverse events.

A population-based analysis of the impact of 1 vs. 2 doses of mitomycin on patterns of failure of anal cancer patients treated with concurrent chemoradiotherapy

PurposeWe report the impact of 1 vs. 2 doses of mitomycin-C (MMC) based chemoradiation (CRT) on patterns of treatment failure and long-term patient outcomes in anal squamous cell carcinoma (ASCC) and the predictors for locoregional failure (LRF) and distant metastasis (DM). MethodsIn this population-based study, we identified all patients with anal cancer in our province treated radically with radiation and concurrent 5-Fluorouracil (5FU) and 1 vs. 2 doses of MMC between the years 2000-2019. The primary outcomes analyzed were locoregional recurrence (LRR), disease free survival (DFS), ASCC cancer-specific survival (ASCC-CSS) and overall survival (OS). Results451 patients were identified. 272 (60%) patients received 1 cycle of MMC (MMC1) and 179 (40%) received 2 cycles (MMC2) as part of the CRT regimen. The median follow-up was 57 (36-252) and 97 (38-239) months for MMC1 and MMC2, respectively. Cox Regression analysis showed stage IIIb and IIIc were associated with worse locoregional recurrence free survival (RFS) (HR=2.851, p=<0.001) and distant RFS (HR=3.391, p=<0.001). Similarly, stage IIIb and IIIc patients had poorer DFS (HR 3.439, p=<0.001), ASCC-SS (HR 3.729, p=<0.001) and OS (2.230, p=<0.001). The use of MMC2 showed a positive impact on improved ASCC-SS (HR 0.569, p=0.029) and distant RFS (HR 0.555, p=0.040) in patients with stage IIIb and IIIc. ConclusionsOur analysis showed that 1 vs. 2 cycles of MMC along with 5FU and radiation is associated with comparable treatment outcomes in general. However, in patients with stage IIIb and IIIc cancer, 2 doses of MMC were associated with improved ASCC-SS and distant DFS.

Socioeconomic Disparities in Anal Cancer: Effect on Treatment Delay and Survival.

Socioeconomic inequities have implications for access to health care and may be associated with disparities in treatment and survival. To investigate the impact of socioeconomic inequities on time to treatment and survival of anal squamous-cell carcinoma. This is a retrospective study using a nationwide data set. The patients were selected from the National Cancer Database and enrolled from 2004 to 2016. We identified patients with stage I to III squamous-cell carcinoma of the anus who were treated with chemoradiation therapy. Socioeconomic factors, including race, insurance status, median household income, and percentage of the population with no high school degrees, were included. The association of these factors with treatment delay and overall survival was investigated. A total of 24,143 patients who underwent treatment for grade I to III squamous-cell carcinoma of the anus were identified. The median age was 60 years, and 70% of patients were women. The median time to initiation of treatment was 33 days. Patients from zip codes with lower median income, patients with a higher percentage of no high school degree, and patients with other government insurance followed by Medicaid insurance had treatment initiated after 60 days from diagnosis. Kaplan-Meier survival analysis showed that the late-treatment group had worse overall survival compared to the early treatment group (98 vs 125 months; p < 0.001). No detailed information is available about the chemoradiotherapy regimen, completion of treatment, recurrence, disease-free survival, and individual-level socioeconomic condition and risk factors. Patients from communities with lower median income, level of education, and enrolled in public insurance had longer time to treatment. Lower socioeconomic status was also associated with poorer overall survival. These results warrant further analysis and measures to improve access to care to address this disparity. See Video Abstract . ANTECEDENTES:Las desigualdades socio-económicas tienen implicaciones en el acceso a la atención médica y pueden estar asociadas con disparidades en el tratamiento y la sobrevida.OBJETIVO:Indagar el impacto de las desigualdades socio-económicas sobre el tiempo de retraso en el tratamiento y la sobrevida en casos de carcinoma a células escamosas del ano (CCEA).DISEÑO:Estudio retrospectivo utilizando un conjunto de datos a nivel nacional.AJUSTES:Todos aquellos pacientes inscritos entre 2004 a 2016 y que fueron seleccionados de la Base Nacional de Datos sobre el Cáncer.PACIENTES:Identificamos pacientes con CCEA en estadíos I-III y que fueron tratados con radio-quimioterápia.PRINCIPALES MEDIDAS DE RESULTADOS:Se incluyeron factores socio-económicos tales como la raza, el tipo de seguro de salud, el ingreso familiar medio y el porcentaje de personas sin bachillerato de secundaria (SBS). Se investigó la asociación entre estos factores con el retraso en iniciar el tratamiento y la sobrevida global.RESULTADOS:Se identificaron un total de 24.143 pacientes que recibieron tratamiento para CCEA estadíos I-III. La mediana de edad fue de 60 años donde 70% eran de sexo femenino. La mediana del tiempo transcurrido desde el diagnóstico hasta el inicio del tratamiento fue de 33 días. Los pacientes residentes en zonas de código postal con ingresos medios más bajos, con un mayor porcentaje de individuos SBS y los pacientes con otro tipo de seguro gubernamental de salud, seguidos del seguro tipo Medicaid iniciaron el tratamiento solamente después de 60 días al diagnóstico inicial de CCEA. El análisis de Kaplan-Meier de la sobrevida mostró que el grupo de tratamiento tardío tuvo una peor supervivencia general comparada con el grupo de tratamiento precoz o temprano (98 frente a 125 meses; p <0,001).LIMITACIONES:No se dispone de información detallada sobre el tipo de radio-quimioterapia utilizada, ni sobre la finalización del tratamiento o la recurrencia, tampoco acerca de la sobrevida libre de enfermedad ni sobre las condiciones socio-económicas o aquellos factores de riesgo a nivel individual.CONCLUSIÓN:Los pacientes de comunidades con ingresos medios más bajos, con un nivel de educación limitado e inscritos en un seguro público tardaron mucho más tiempo en recibir el tratamiento prescrito. El nivel socio-económico más bajo también se asoció con una sobrevida global más baja. Los presentes resultados justifican mayor análisis y medidas mas importantes para mejorar el acceso a la atención en salud y poder afrontar esta disparidad. (Traducción-Dr. Xavier Delgadillo ).