Completion Of Concurrent Chemoradiotherapy Research Articles

Phase 3 KEYNOTE-992 study of pembrolizumab plus chemoradiotherapy versus placebo plus chemoradiotherapy in patients with muscle-invasive bladder cancer (MIBC).

TPS720 Background: Concurrent chemoradiotherapy (CRT) is a recommended treatment option for patients (pts) with MIBC who seek a bladder-preserving alternative to radical cystectomy and/or not candidates for radical cystectomy. The anti–PD-1 antibody pembrolizumab is approved for metastatic bladder cancer and non–muscle-invasive bladder cancer (NMIBC). The randomized, double-blind, phase 3 KEYNOTE-992 study (NCT04241185) is evaluating efficacy and safety of pembrolizumab plus CRT versus placebo plus CRT in pts with MIBC who chose bladder preservation. Methods: Eligibility criteria include adultswho have a histologically confirmed initial diagnosis of MIBC (T2-T4aN0M0) with ≥50% urothelial histology, ECOG PS score of 0 to 2, have received no prior therapy with anti–PD-1/L1 or agents directed to another stimulatory or coinhibitory T-cell receptor, and have planned treatment with one of the specified radiosensitizing chemotherapies. Prior treatment for NMIBC with intravesical instillation therapy such as BCG or intravesical chemotherapy is permitted. Approximately 636 pts will be randomly assigned 1:1 to receive pembrolizumab 400 mg IV or placebo IV every 6 weeks for up to 9 cycles, both with CRT. Investigator’s choice of chemotherapy will be specified before random assignment. Pts will be stratified by ECOG PS (0 and 1 vs 2), PD-L1 combined positive score (<10 vs ≥10), T stage (T2 vs T3 and T4), and geographic region (United States vs European Union vs rest of the world). Radiosensitizing chemotherapy will be cisplatin monotherapy (35 mg/m2 IV weekly on day 1), 5-fluorouracil (500 mg/m2 on days 1-5 and days 22-26) plus mitomycin C (12 mg/m2 on day 1), or gemcitabine monotherapy (27 mg/m2 IV twice weekly on days 1 and 4). Radiation therapy will be conventional radiotherapy consisting of 64 Gy at 2 Gy/fraction over 6.5 weeks (whole bladder with or without pelvic nodes) or hypofractionated radiotherapy consisting of 55 Gy at 2.75 Gy/fraction over 4 weeks (whole bladder only). Imaging via CT and CT urography or magnetic resonance urography will be performed 10 weeks after completion of CRT, every 12 weeks until the end of year 2, then every 24 weeks thereafter. Adverse events (AEs) will be monitored throughout the study and up to 30 days after cessation of treatment (90 days for serious AEs). Primary end point is bladder-intact event-free survival (defined as time from random assignment to first documented occurrence of residual/recurrent MIBC, nodal or distant metastases, radical cystectomy, or death from any cause) as assessed by blinded independent central review and/or central pathology review. Secondary end points are overall survival, metastasis-free survival, time to cystectomy, time to occurrence of NMIBC, safety and tolerability, and patient-reported outcomes. Enrollment is ongoing in Asia, Australia, Europe, North America, and South America. Clinical trial information: NCT04241185 .

Low-Dose Fractionated Radiotherapy Combined with Neoadjuvant Chemotherapy for T3-4 Nasopharyngeal Carcinoma Patients: The Preliminary Results of a Phase II Randomized Controlled Trial

Over 70% of NPC patients were local advanced NPC (LANPC). The 5-year local recurrence-free survival rate is only 70% in T3-4 patients. Neoadjuvant chemotherapy (NACT) followed with concurrent chemoradiotherapy (CCRT) was recommended for LANPC patients. Low-dose fractionated radiotherapy (LDFRT), which is <100cGy, induces enhanced cell killing by the hyper-radiation sensitivity phenomenon and potentiates effects of chemotherapy. The synergy of LDFRT and NACT has not been used in the clinical practice and few studies focused on it. A single arm study found the ORR of primary site was improved to 90% for head and neck squamous carcinoma patients treated with LDFRT and NACT. Our previous study found the ORR of lymph nodes was higher in LDFRT group for high-risk LANPC patients. However, another study showed there was no significant difference between LDFRT and control group for LANPC patients. So, we aimed to investigate the potential efficacy of this novel neoadjuvant therapy for T3-4 NPC patients. A total of 60 pathological confirmed T3-4 (UICC/AJCC8th) NPC patients were prospectively enrolled in our study. They were randomly assigned to two groups. For the LDFRT group, the patients received 3 cycles of NACT (docetaxel 75mg/m2 D1, cisplatin 80mg/m2 D1) with LDFRT, and followed with CCRT. LDFRT was delivered as 50cGy per fraction twice a day to primary site on D1,2 for each cycle of NACT. The patients in the control group only received NACT and followed with CCRT. All the patients underwent IGRT. RECIST criteria and CTCAE 5.0 was used to evaluate the ORR and toxicity at post-NACT and the completion of CCRT. From February 2022 to December 2022, 60 T3-4 NPC patients were included, and 30 patients for each group. For the primary site, the median volume reduction rate and the ORR after NACT was significantly improved in LDFRT group (69.27% vs 40.10%, p<0.001;93.33% vs 73.33%, p = 0.038). For the median volume reduction rate of primary site and lymph node, it was also obviously improved in LDFRT group (86.59% vs 55.43%, p<0.001). Though there was a tendency of ORR improvement in LDFRT group, but no significant difference (96.67% vs 83.33%, p = 0.195). After the completion of CCRT, the median volume reduction rate of primary site had an increased tendency in LDFRT group (96.16% vs 88.3%, p = 0.065), but the ORR had no statistical significance (LDFRT group: CR 45.8%, PR 54.2%; control group: CR 37.5%, PR 62.5%). For the toxicity, the incidence of grade 3-4 adverse events had no difference between two groups (p = 0.786). No grade 5 adverse events occurred. LDFRT combined with NACT could obviously improve the median volume reduction rate and ORR of primary tumor for T3-4 NPC patients, and the toxicity was similar and tolerable. This novel treatment could be a promising strategy to improve treatment response and needed to be confirmed further.

The effect of early oral nutritional supplements on improving nutritional outcomes and radiation-induced oral mucositis for nasopharyngeal carcinoma patients undergoing concurrent chemoradiotherapy.

To explore the value of early oral nutritional supplements (ONS) in patients with nasopharyngeal carcinoma (NPC) treated with concurrent chemoradiotherapy (CCRT). Patients with newly diagnosed II-IVA stage NPC were analyzed and divided into Early and Routine ONS groups according to whether they received early ONS at the beginning of CCRT. Changes in nutritional indicators, incidence of treatment-related toxicity, radiation interruption, and completion of CCRT were compared. In total, 161 patients with NPC were analyzed, including 72 in the Early ONS group and 89 in the Routine ONS group. Multivariate analysis showed that early ONS was an independent protective factor for concurrent chemotherapy ≥2 cycles, and a protective factor against ≥grade 3 radiation-induced oral mucositis (RIOM) and weight loss >5%. In stage III-IVA patients, early ONS was beneficial in decreasing the risk of severe malnutrition. Early ONS can improve nutritional outcomes, reduce RIOM, and enhance treatment adherence.

Low-dose fractionated radiotherapy combined with neoadjuvant chemotherapy for T3-4 nasopharyngeal carcinoma patients: Preliminary results of a phase II randomized controlled trial.

6049 Background: Over 70% of NPC patients were local advanced NPC (LANPC). The 5-year local recurrence-free survival rate is only 70% in T3-4 patients. Neoadjuvant chemotherapy (NACT) followed with concurrent chemoradiotherapy (CCRT) was recommended for LANPC patients. Low-dose fractionated radiotherapy (LDFRT), which is &lt; 100cGy, induces enhanced cell killing by the hyper-radiation sensitivity phenomenon and potentiates effects of chemotherapy. The synergy of LDFRT and NACT has not been used in the clinical practice and few studies focused on it. A single arm study found the ORR of primary site was improved to 90% for head and neck squamous carcinoma patients treated with LDFRT and NACT. Our previous study found the ORR of lymph nodes was higher in LDFRT group for high-risk LANPC patients. However, another study showed there was no significant difference between LDFRT and control group for LANPC patients. So, we aimed to investigate the potential efficacy of this novel neoadjuvant therapy for T3-4 NPC patients. Methods: 60 pathological confirmed T3-4 (UICC/AJCC8th) NPC patients were prospectively enrolled in our study. They were randomly assigned to two groups. For the LDFRT group, the patients received 3 cycles of NACT (docetaxel 75mg/m2 D1, cisplatin 80mg/m2 D1) with LDFRT, and followed with CCRT. LDFRT was delivered as 50cGy per fraction twice a day to primary site on D1,2 for each cycle of NACT. The patients in the control group only received NACT and followed with CCRT. All the patients underwent IGRT. RECIST criteria and CTCAE 5.0 was used to evaluate the ORR and toxicity at post-NACT and the completion of CCRT. Results: from Feb 2022 to Dec 2022, 60 T3-4 NPC patients were included, and 30 patients for each group. For the primary site, the median volume reduction rate and the ORR after NACT was significantly improved in LDFRT group (69.27% vs 40.10%, p&lt; 0.001;93.33% vs 73.33%, p= 0.038). For the median volume reduction rate of primary site and lymph node, it was also obviously improved in LDFRT group (86.59% vs 55.43%, p&lt; 0.001). Though there was a tendency of ORR improvement in LDFRT group, but no significant difference (96.67% vs 83.33%, p= 0.195). After the completion of CCRT, the median volume reduction rate of primary site had an increased tendency in LDFRT group (96.16% vs 88.3%, p= 0.065), but the ORR had no statistical significance (LDFRT group: CR 45.8%, PR 54.2%; control group: CR 37.5%, PR 62.5%). For the toxicity, the incidence of grade 3-4 adverse events had no difference between two groups ( p= 0.786). No grade 5 adverse events occurred. Conclusions: LDFRT combined with NACT could obviously improve the median volume reduction rate and ORR of primary tumor for T3-4 NPC patients, and the toxicity was similar and tolerable. The novel treatment could be a promising strategy to improve treatment response, and needed to be confirmed further. Clinical trial information: NCT05503914 .

Can the apparent transverse relaxation rate (R2*) evaluate the efficacy of concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma? a preliminary experience

BackgroundThe use of the apparent transverse relaxation rate (R2*) in nasopharyngeal carcinoma (NPC) has not been previously reported in the literature. The aim of this study was to investigate the role of the R2* value in evaluating response to concurrent chemoradiotherapy (CCRT) in patients with NPC.MethodsForty-one patients with locoregionally advanced NPC confirmed by pathology were examined by blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) before and after CCRT, and conventional MRI was performed 3 months after the completion of CCRT. All patients were divided into a responding group (RG) and a nonresponding group (NRG), according to MRI findings 3 months after the end of treatment. The R2* values before (R2*preT) and after (R2*postT) CCRT and the ΔR2* (ΔR2*=R2*postT – R2*preT) were calculated in the tumor.ResultsAmong the 41 patients, 26 were in the RG and 15 were in the NRG. There was no statistical difference in the R2*preT between RG and NRG (P = 0.307); however, there were significant differences in R2*postT and ΔR2* (P < 0.001). The area under the curve of R2*postT and ΔR2* for predicting the therapeutic response of NPC was 0.897 and 0.954, respectively, with cutoff values of 40.95 and 5.50 Hz, respectively.ConclusionThe R2* value can be used as a potential imaging indicator to evaluate the therapeutic response of locoregionally advanced NPC.

A Propensity-Matched Retrospective Comparative Study with Historical Control to Determine the Real-World Effectiveness of Durvalumab after Concurrent Chemoradiotherapy in Unresectable Stage III Non-Small Cell Lung Cancer

This study aimed to add real-world evidence to the literature regarding the effectiveness and safety of durvalumab consolidation (DC) after concurrent chemoradiotherapy (CCRT) in the treatment of unresectable stage III non-small cell lung cancer (NSCLC). Using a hospital-based NSCLC patient registry and propensity score matching in a 2:1 ratio, we conducted a retrospective cohort study of patients with unresectable stage III NSCLC who completed CCRT with and without DC. The co-primary endpoints were 2-year progression-free survival and overall survival. For the safety evaluation, we evaluated the risk of any adverse events requiring systemic antibiotics or steroids. Of 386 eligible patients, 222 patients-including 74 in the DC group-were included in the analysis after propensity score matching. Compared with CCRT alone, CCRT with DC was associated with increased progression-free survival (median: 13.3 vs. 7.6 months, hazard ratio[HR]: 0.63, 95% confidence interval[CI]: 0.42-0.96) and overall survival (HR: 0.47, 95% CI: 0.27-0.82) without an increased risk of adverse events requiring systemic antibiotics or steroids. While there were differences in patient characteristics between the present real-world study and the pivotal randomized controlled trial, we demonstrated significant survival benefits and tolerable safety with DC after the completion of CCRT.

Primary Radiation as an Alternative Option for Early-Stage Cervical Cancer

The standard of care for locally advanced cervical cancer is concurrent chemoradiotherapy (CRT) followed by image guided brachytherapy. Surgery is not indicated for initial debulking before initiation of CRT or as adjuvant treatment after completion of CRT.1 However, the question remains: what is the best strategy for the management of early-stage, operable disease?

Leptomeningeal carcinomatosis in a patient with recurrent unresectable squamous cell carcinoma of the retromolar trigone—a brief report

BackgroundThe reported incidence of leptomeningeal carcinomatosis is 3–8% in patients with solid tumours. More commonly, it has been described in the setting of advanced cancers of the lung, breast and malignant melanoma.Case presentationA 50-year-old diabetic patient with recurrent unresectable squamous cell carcinoma (SCC) of the right retromolar trigone (rT4bN0M0) presented with severe low backache and weakness in bilateral lower limbs 20 days after the completion of concurrent chemoradiotherapy. Contrast-enhanced MRI of the spine showed multiple nodular enhancing leptomeningeal lesions at the lumbar level and an intramedullary T2/FLAIR-hyperintense longitudinal lesion involving the central cord from C2 to C7 vertebral levels, suggestive of leptomeningeal metastases. Cerebrospinal fluid (CSF) analysis revealed pleocytosis, elevated protein and markedly decreased glucose. The CSF cytology revealed scattered large atypical cells, suspicious for metastasis. Non-contrast MRI of the brain showed a T2/FLAIR-hyperintense lesion involving the right caudate nucleus suggestive of either an acute infarct with haemorrhagic transformation or a haemorrhagic brain metastasis. During assessment, he had high-grade fever and was started on empirical intravenous antibiotics (ceftriaxone, vancomycin and subsequently meropenem) in line with the management for acute bacterial meningitis. Gram staining of CSF did not demonstrate the presence of any bacteria and the specimen was sterile on culture. He did not respond to empirical antibiotics, had a progressive downhill course and eventually died due to aspiration pneumonia.ConclusionThis brief report highlights the importance of awareness of leptomeningeal carcinomatosis as a possible cause of backache with sensorimotor deficit and autonomic dysfunction in a previously treated case of head and neck SCC.

MRI-based radiomics for pretreatment prediction of response to concurrent chemoradiotherapy in locally advanced cervical squamous cell cancer.

To investigate the value of magnetic resonance imaging (MRI)-based radiomics in predicting the treatment response to concurrent chemoradiotherapy (CCRT) in patients with locally advanced cervical squamous cell cancer (LACSC). In total, 198 patients (training: n = 138; testing: n = 60) with LACSC treated with CCRT between January 2014 and December 2019 were retrospectively enrolled in this study. Responses were evaluated by MRI and clinical data performed at one month after completion of CCRT according to RECIST standards, and patients were divided into the residual group and nonresidual group. Overall, 200 radiomics features were extracted from T2-weighted imaging and apparent diffusion coefficient maps. The radiomics score (Rad-score) was constructed with a feature selection strategy. Logistic regression analysis was used for multivariate analysis of radiomics features and clinical variables. The performance of all models was assessed using receiver operating characteristic curves. Among the clinical variables, tumor grade and FIGO stage were independent risk factors, and the areas under the curve (AUCs) of the clinical model were 0.741 and 0.749 in the training and testing groups. The Rad-score, consisting of 4 radiomics features selected from 200 radiomics features, showed good predictive performance with an AUC of 0.819 in the training group and 0.776 in the testing group, which were higher than the clinical model, but the difference was not statistically significant. The combined model constructed with tumor grade, FIGO stage, and Rad-score achieved the best performance, with an AUC of 0.857 in the training group and 0.842 in the testing group, which were significantly higher than the clinical model. MRI-based radiomics features could be used as a noninvasive biomarker to improve the ability to predict the treatment response to CCRT in patients with LACSC.

EP05.01-021 Radiation Dose to Cardiac Substructures and the Incidence of Cardiac Events in Patients with Stage III NSCLC Receiving CCRT

Cardiac toxicities after radiation therapy (RT) in lung cancer patients (pts) have been increasingly recognized as an important factor in clinical outcomes. Here we investigated the impact of radiation doses to the heart and cardiac substructures (left atrium (LA), left ventricle (LV), right atrium (RA) and right ventricle (RV)) on the incidence of cardiac events following completion of concurrent chemoradiotherapy (CCRT).

Treatment patterns and prognosis of patients with inoperable stage III NSCLC after completion of concurrent chemoradiotherapy ± immune checkpoint inhibition: a decade-long single-center historical analysis

PurposeTo investigate the impact of treatment time and patterns in inoperable stage III non-small cell lung cancer (NSCLC) following concurrent chemoradiotherapy (cCRT) ± immune checkpoint inhibitors (ICIs).MethodsPatients were stratified by treatment year: A (2011–2014), B (2015–2017) and C (2018–2020). Tumor- and treatment-related characteristics regarding locoregional recurrence-free survival (LRRFS), progression-free survival (PFS) and overall survival (OS) were investigated.ResultsOne hundred and thirty-six consecutive patients were analyzed. All patients completed thoracic radiotherapy (TRT) to a total dose ≥ 60.0 Gy; 36 (26%) patients received ICI. Median PFS in subgroups A, B and C was 8.0, 8.2 and 26.3 months (p = 0.007). Median OS was 19.9 months, 23.4 months and not reached (NR), respectively. In group C, median LRRFS and PFS were 27.2 vs. NR; and 14.2 vs. 26.3 months in patients treated with and without ICI. On multivariate analysis planning target volume (PTV) ≥ 700 cc was a negative prognosticator of LRRFS (HR 2.194; p = 0.001), PFS (HR 1.522; p = 0.042) and OS (HR 2.883; p = 0.001); ICI was a predictor of LRRFS (HR 0.497; p = 0.062), PFS (HR 0.571; p = 0.071) and OS (HR 0.447; p = 0.1). In the non-ICI cohort, multivariate analyses revealed PTV ≥ 700 cc (p = 0.047) and a maximum standardized uptake value (SUVmax) ≥ 13.75 (p = 0.012) were predictors of PFS; PTV ≥ 700 cc (p = 0.017), SUVmax ≥ 13.75 (p = 0.002) and a total lung V20 ≥ 30% (V20 ≥ 30) (p < 0.05) were predictors of OS.ConclusionsPatients treated after 2018 had improved survival regardless of ICI use. Implementation of ICI resulted in further significant increase of all tested survival endpoints. PTV ≥ 700 cc and ICI were only prognosticators for LRRFS, PFS and OS in the analyzed cohort.

Exploratory analysis using cfDNA-based fragmentomics to predict disease recurrence in limited disease small cell lung cancer.

8569 Background: The current standard of care (SOC) for limited disease (LD) small cell lung cancer (SCLC) is definitive concurrent chemoradiotherapy (CCRT). Despite the high response rate to SOC, up to 70% of the patients potentially experience disease recurrence and fail to show the prolonged clinical benefit. We investigated the feasibility of cell-free DNA (cfDNA) based genomic alteration and fragmentomic analysis using pre-and post-treatment samples to investigate the predictive value of disease recurrence in LD-SCLC. Methods: The blood sample from fifty LD-SCLC who were treated with definitive CCRT were collected before and after the treatment. Target sequencing, AlphaLiquid scan (IMBdx, Korea), composed of 106 target genes, was conducted using cfDNA and peripheral blood mononuclear cells. Based on the recurrence-free survival (RFS) interval of 12 months, patients were categorized into group with persistent response (PeR, n = 29) and non-PeR (n = 21). Fragmentomics analyses were collected using the proportion of cfDNA fragments sized in P1 (100 – 155 bp) and P2 (160 – 180 bp) ranges. Results: Initial analysis was conducted based on the gene of interest. Patients with RB1 mutation (n = 11) detected in follow-up sample demonstrated significant shorter RFS compared to the RB1 wild type (WT) patients (n = 39) (7.9 mon. vs. NR, P = 0.002). Among the patients who were available for our fragmentomics analysis in follow up samples (n = 19), non-PeR (n = 9) group were significantly high in P1 range ( P = 0.003) and low in P2 range ( P = 0.002) compared to PeR group (n = 10). AUCs using the fragment proportion in P1, proportion in P2, and the fragmentation ratio (proportion in P1 / proportion in P2), were 0.889, 0.911, and 0.889, respectively. The survival analysis using fragmentation ratio showed significantly longer RFS in fragmentation ratio low group compared to the high group (7.6 mon. vs. NR, P = 0.002). Integrating RB1 mutation status with fragmentation ratio, patients with both RB1 WT and fragmentation ratio low (n = 9) showed the most favorable outcomes ( P = 0.006). On the contrary, patients with either RB1 mutated or high in fragmentation ratio (n = 10) showed median RFS of rest than 12 months. Conclusions: In this study, we investigated the clinical feasibility of cfDNA detected mutation and size of the fragment in disease recurrence of LD-SCLC using the sample collected before and after definitive CCRT. It is observed that patients with either RB1 mutation or high fragmentation ratio detected from cfDNA after the completion of CCRT are likely to experience early disease recurrence. Our findings suggest that cfDNA could provide supplementary information in predicting early treatment failure and support the clinical decision in selecting high-risk patients who might need intense monitoring and additional consolidative treatment.

Propensity-matched analysis of concurrent/sequential versus sequential immune checkpoint inhibition in inoperable stage III NSCLC patients treated with chemoradiotherapy.

e20589 Background: Durvalumab maintenance treatment after completion of concurrent chemoradiotherapy (CRT) in patients with inoperable stage III NSCLC is the international standard. In this propensity-matched analysis, we prospectively evaluated the role of concurrent/sequential versus sequential immune checkpoint inhibition. Methods: Between 10/1/2016 and 12/31/2020, 39 NSCLC patients in stage IIIA/B/C were analyzed. 11 (28%) patients received concurrent/sequential PD-1 inhibition (nivolumab) and 28 (72%) patients received sequential PD-L1 inhibition (durvalumab) up to one year after the end of CRT. A 1:2 propensity score matching (PSM) using age, gender, T category and histology was performed to reduce selection bias and address for confounding factors (n = 33, 11 patients receiving nivolumab (SIM-cohort), 22 patients receiving durvalumab (SEQ-cohort). Treatment-related adverse events were assessed weekly during the CRT and at 6 weeks, 3,6,9, and 12 months after the end of CRT. Results: The median follow-up time of the overall cohort, SIM-I cohort, and SEQ-I cohort was 27.6, 33.3, and 26.5 months after CRT, respectively. For the entire cohort median survival (OS) was not reached; median progression-free survival (PFS) achieved 26.3 months. In the SIM-cohort, median PFS was 22.8 months and median OS was not reached. In the SEQ-cohort, neither median PFS nor OS was reached. PFS at 12/24 months was 82/44% in the SIM-cohort and 57/57% in the SEQ-cohort (p = 0.714), respectively. In the SIM-cohort, 18.2% of patients showed grade III pneumonitis; in the SEQ-cohort 13.6% (p = 0.735). Grade 4 and 5 toxicities were not observed. Conclusions: Both concurrent/sequential and sequential immune checkpoint inhibition shows a favorable side effect profile and promising survival in terated patients. Concurrent immunotherapy did not result in an improved outcome (PFS, OS) compared to sequential approach. However, our propensity-matched analysis found that concurrent immunotherapy was associated with a non-significant moderate increase in grade III pneumonitis.

A phase II study of durvalumab (MEDI4736) immediately after completion of chemoradiotherapy in unresectable stage III non–small cell lung cancer: TORG1937 (DATE study).

8536 Background: Concurrent chemoradiotherapy followed by durvalumab maintenance for up to 12 months is the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). However, the best timing of starting durvalumab after completion of chemoradiation has not been identified. Progression-free survival (PFS) and overall survival (OS) were better in the subgroup of patients administered durvalumab within 14 days after last radiation to randomization according to the PACIFIC study (Antonia SJ, et al. 2017, 2018 NEJM). Methods: This study was a prospective, single-arm, multicenter, phase II clinical trial. Eligibility criteria included patients with unresectable stage III NSCLC, ECOG PS 0-1, age &lt; 75 years old. Patients who did not have disease progression after definitive concurrent chemoradiotherapy (CCRT) (chemotherapy: 2 cycles of platinum-based doublet chemotherapy, radiotherapy: 60 Gy/30 Fr) received durvalumab (10 mg/kg, every 2 weeks for up to 12 months) from the next day (allowed up to 5 days) after last radiation. The primary endpoint was 1-year PFS rate from registration assessed by an independent review committee. The planned sample size was 47 with a threshold value of 50% based on results of the PACIFIC study, an expected value of 63%, one-sided alpha of 20% and power of 80% in 1-year PFS rate. Results: From January 2020 to August 2020, 50 patients were enrolled from 16 institutions and 47 patients were evaluable for efficacy and safety. Forty-two patients received durvalumab maintenance therapy. Patient characteristics were: male/female 41/6; median age 65 (range 42-75); ECOG PS 0/1 28/19; IIIA/IIIB/IIIC 19/21/7. The 1-year PFS rate from registration was 75.0% (60% CI: 69.0 to 80.0). The 1-year OS rate from registration was 97.7% (95%CI: 84.6 to 99.7). ORR, median PFS and median OS were 78.7%, 14.2 months (95%CI: 13.4 to not reached (NR)) and NR, respectively. Grade 3/4 adverse events were pneumonitis (4.3%), neutropenia (44.7%), febrile neutropenia (4.3%). There was no treatment-related death. Conclusions: Our study met the primary endpoint. Durvalumab can be safely administered immediately after completion of CCRT for patients with unresectable stage III NSCLC, no additional or unexpected toxicity occurred as a reference to the PACIFIC study. Clinical trial information: jRCTs031190117.

Tumor response evaluation by combined modalities of chest magnetic resonance imaging and computed tomography in locally advanced non-small cell lung cancer after concurrent chemoradiotherapy

PurposeThis study aimed to explore the role of a modified criteria for assessing tumor response to concurrent chemoradiotherapy (CCRT) in locally advanced non-small cell lung cancer (LA-NSCLC), using the combined modalities of anatomical and functional MRI and CT. Materials and methodsOne hundred and fifty-three patients with LA-NSCLC who underwent CCRT with continuous chest MRI and CT follow-up were analyzed. The tumor response to CCRT was evaluated two months after the completion of CCRT. The RECIST criteria (CT imaging) and modified criteria (combined chest MRI and CT imaging) were compared and validated on follow-up imaging. The chest MRI scan analysis included T1C, T2fs, DWI imaging and the apparent diffusion coefficient values. Progression free survival (PFS) ≥ 18 months was used as a surrogate endpoint of complete response to analyze the accuracy of tumor response assessment. ResultsEight (5.2%) patients were considered to have complete response (CR) by the RECIST criteria while fifty-five (35.9%) were considered to have CR (CT + MRI) by the modified criteria. Using PFS ≥ 18 months as a surrogate for CR, the sensitivity and specificity of the modified criteria were 71.2% and 90.8% (AUC = 0.810, 95%CI 0.735–0.885), but were 9.1% and 97.7%, respectively, for the RECIST criteria (AUC = 0.534, 95%CI 0.441–0.627). The median PFS was 58.4 months for patients with CR (CT + MRI) and 9.7 months for those with non-CR (P < 0.001). Multivariate analysis showed that the tumor response evaluated by the modified criteria [CR (CT + MRI) vs. non-CR] was an independent factor for both PFS (HR 0.182, 95%CI 0.088–0.373, P < 0.001) and overall survival (HR 0.134, 95%CI 0.044–0.410, P < 0.001). ConclusionsCombined multi-parameter MRI and CT imaging could improve the accuracy of tumor response assessment in LA-NSCLC patients after definitive CCRT, therefore contributed to the risk stratification and survival prediction for clinical practice.

Diffusion Weighted and Dynamic Contrast Enhanced Magnetic Resonance Imaging in Carcinoma of Cervix: Role of Apparent Diffusion Coefficient Value and Time Intensity Curve Pattern in Chemoradiotherapeutic Response Evaluation

Introduction: Magnetic resonance imaging (MRI) is a widely used imaging modality in the imaging evaluation of carcinoma of cervix. The aim of our study was to evaluate the response in carcinoma cervix patients following chemoradiotherapy by Diffusion weighted (DW-MRI) and Dynamic contrast enhanced-MRI (DCE-MRI). Methods: 21 inoperable biopsy proven patients (mean age 48.43 years) of carcinoma cervix were included in the study. All patients underwent MRI (conventional, DW and DCE) of the pelvis thrice. Baseline MRI, Post chemotherapy MRI after neoadjuvant chemotherapy and Post chemoradiotherapy MRI after completion of concurrent chemoradiotherapy. Post treatment apparent diffusion coefficient(ADC) values and Time intensity curve(TIC) pattern were compared with baseline values. Results: Baseline meanADC value of all patients was 0.82 x10-3 mm2/s. After completion of treatment, 18 patients showed complete resolution of tumor and showed 0.50 x10-3 mm2/s increase in meanADC value from baseline MRI which was significantly higher than remaining 3 patients with residual tumor (0.50 x10-3 mm2/s v/s 0.17 x10-3 mm2/s). ADC threshold value of 1.15 x10-3 mm2/s was defined, differentiating the residual tumor from the healthy cervical tissue after chemoradiation. On post treatment MRI, 17 out of 18 patients with complete resolution of tumor showed increasing trend of enhancement on TIC and only one patient showed plateau pattern. 2 of the 3 patients with residual tumor showed washout pattern and one patient showed plateau pattern. Conclusion: ADC values and TIC pattern differ in patients with complete response to chemoradiotherapy from patients with residual tumor, so helps in differentiating residual tumor from cancer free cervix. Keywords: Carcinoma of cervix; Chemoradiotherapy; Diffusion weighted MRI; Dynamic contrast enhanced MRI; Time intensity curve.

Usefulness of Short-Term Imaging and Squamous Cell Carcinoma Antigen to Early Predict Response to Concurrent Chemoradiotherapy in Patients With Cervical Cancer.

ObjectiveThe objective is to investigate the factors that can predict early treatment response in patients receiving concurrent chemoradiotherapy (CCRT) for cervical cancer.MethodsWe assessed clinical factors and treatment response in patients who underwent CCRT for cervical cancer at four time points: initial, 2.5 weeks, 6 weeks after starting CCRT, and 3 months after completing CCRT. The final treatment response was determined by positron emission tomography-computed tomography (PET-CT) 3 months after completion of CCRT. Patients were divided into two groups according to the final treatment response: complete response (CR) group or non-CR group. And the early CCRT response prediction model was developed using stepwise multivariate logistic regression analysis.ResultsOf the 62 patients who underwent CCRT for cervical cancer, 57 patients who completed all 4 time points examinations were included in the analyses and classified as CR (n = 32) and non-CR (n = 25) group. Tumor volume and serum squamous cell carcinoma antigen (SCC Ag) of the initial, 2.5 weeks, and 6 weeks after CCRT were significantly associated with the final treatment response. For the early treatment response prediction model, we selected patient age, tumor volume, and SCC Ag measured at initial and 2.5 weeks of CCRT as variables, and the equation of the final model was yielded. Using a cutoff of 0.433, this model had a sensitivity of 72.0%, a specificity of 84.4%, and a probability of 0.8225 (P < .0001).ConclusionShort-term (at 2.5 weeks after starting CCRT) measurements of tumor volume and serum SCC Ag were significant predictors of response to CCRT in patients with cervical cancer.

Early Efficacy Prediction of Nasopharyngeal Carcinoma Based on 3D-ADC Acquired During Radiotherapy: A Phase II Prospective Study

Concurrent chemoradiotherapy (CCRT) is the main treatment model for locally advanced nasopharyngeal carcinoma (LANPC). Previous study found the apparent diffusion coefficient (ADC) value of primary tumor partly correlated to prognosis for NPC patients. Recent studies reported that the changes of ADC value at pre- and post-treatment was a more sensitive predictor for prognosis. The prognosis for LANPC patients who received the same treatment strategy varies greatly. The early predictor was urgently needed to help for adjusting the treatment strategy. Thus, we aimed to observe the dynamic changes of ADC of gross target volume (GTV) and metastatic lymph nodes (LN) for NPC patients during radiotherapy (RT), and explored the potential correlations between ADC changes and treatment response.A total of 50 squamous NPC (II-IVa, the 8th TNM staging system) patients treated with CCRT were enrolled in this study. All patients received a planned total dose of 66 to 70Gy in 33 fractions at 5 fractions per week using Image-guided intensity modulated radiotherapy (IGRT). The regimen was cisplatin-based chemotherapy for 3 cycles. The patients received diffusion weighted MRI (DWI) scan at pre-RT, the 5th and 15th fractions and immediately post-RT on a 3.0T MRI system (b = 0, 500, 800s/mm2) system. The ADC values of GTV and LN were acquired using a commercially available software. RECIST1.1 criteria was used to evaluate the tumor response. Multivariate analyses were calculated using the logistic regression model. Receiver-operating characteristic (ROC) curve was used to determine the cut-off value of ADC.After the completion of CCRT, the ORR for all the patients was 100% (CR 58%, PR 42%). The mean ADC value of GTV and LN gradually increased from pre-RT to post RT. These changes generally occurred in two stages. For the first stage (from pre-RT to the 5th fraction), the mean ADC value of GTV and LN increased significantly by 20.78% and 22.96% respectively, while the volumes of GTV and LN had minimal changes (GTV:18.42cm3 vs 16.72cm3, LN: 4.67cm3 vs 4.12cm3). As for the second stage (from the 5th fraction to post-RT), the mean ADC value of GTV and LN continued to increase by 45.58% and 41.2% respectively, while the volumes decreased by 86.07% (GTV) and 61.6% (LN). Multivariate analysis showed the mean ADC changes of GTV from pre-RT to the 5th fraction (ΔADC5) was the only independent prognostic factor for treatment response of NPC. ROC showed that the cut-off value for ΔADC5 was 158.82mm2/s (sensitivity:87%; specificity:65%).Mean ADC values of GTV and LN increased dramatically during RT for NPC patients treated with radiotherapy. The mean ADC began to increase at the 5th fraction, while the change of volume was minimal. Early ADC changes at the 5th fraction might be a new and sensitive biomarker to predict the prognosis for NPC patients independently of volume change.

Cisplatin and capecitabine induction chemotherapy in nasopharyngeal carcinoma.

6065 Background: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is now one of the standard treatment for locally advanced nasopharyngeal carcinoma (LANPC). Cisplatin/fluorouracil is one of the recommended IC regimens. Capecitabine is an oral fluoropyrimidine prodrug with higher concentrations of fluorouracil attained in the tumor cells after enzymatic conversions. We conducted this study to evaluate the feasibility, efficacy and safety of cisplatin and capecitabine (PX) IC followed by CCRT in LANPC. Methods: Newly diagnosed patients with LANPC (stage III-IVB according to 7th edition of AJCC/UICC system [TNM-7] and stage III-IVA according to 8th edition [TNM-8) were prospectively recruited from January 2015 to October 2019. They received induction PX (cisplatin: 80mg/m2 on day 1 + capecitabine: 1000mg/m2 twice daily from day 1 to 14 every 3 weeks for 3 cycles) followed by CCRT (cisplatin: 100mg/m2 every 3 weeks for a total of 2-3 cycles concurrent with intensity-modulated radiation therapy [IMRT]). IMRT with doses of 70Gy, 63Gy and 56Gy were delivered to 3 levels of planning target volumes (PTV) (high, intermediate and low risk) respectively and simultaneously in 35 fractions/7 weeks. Tumor response by MRI and CT was evaluated after completion of IC and 16 weeks after completion of CCRT according to RECIST v1.1. All adverse events were graded with NCI CTCAE v4.03. Results: One hundred and forty-five patients were recruited. The stage distributions according to TNM-8 were 82(56.6%) and 63(43.3%) for stage III and IVA, respectively. One hundred and thirty-seven patients completed 3 cycles of induction PX and 122 patients completed IMRT with 2 to 3 cycles of concurrent cisplatin. The median (interquartile range, IQR) tumor regression rates after 2-3 cycles of PX at the nasopharynx (NP) and the neck region (NK) were 51.2% (37.3%-66.5%) and 71.8% (56.7%-81.1%), respectively. At 16 weeks after CCRT, only one patient had residual disease. After a median follow-up of 33 months, 20 treatment failures and 8 deaths were observed. The estimated 2-year progression-free survival (PFS) and overall survival (OS) were 89.8% and 97.2%. The rates of grade 3/4 leukopenia, neutropenia, anemia, nausea/vomiting and electrolyte disturbance during IC were 6.2%, 15.9%, 6.9%, 4.1% and 9.0%, respectively. The corresponding rates were 45.1%, 24.6%, 27.5%, 2.8% and 11.3% during CCRT. Only 1 (0.7%) grade 3/4 hand-foot syndrome and 3 (2.1%) grade 3/4 diarrhea during IC were observed. The rates of grade 3/4 mucositis and dermatitis were 31.0% and 12.7%, respectively. There were no treatment-related deaths. Conclusions: Induction PX followed by CCRT was effective and well tolerated in patients with LANPC. Clinical trial information: NCT03427359.

Pathological response rate in patients who achieve clinical response after neoadjuvant concurrent chemoradiotherapy in localized esophageal cancer

Background: The incidence of esophagus carcinoma is raising and it is the 6th leading cause of mortality. The objective of this study is to determine pathological response rate in patients who achieve clinical response after neo-adjuvant concurrent chemoradiotherapy in locally advanced esophageal cancer presented at a single tertiary care centre in Karachi.&#x0D; Patients and methods: It was a longitudinal study conducted at the Department of Oncology of Jinnah Postgraduate Medical College from May 2017 to July 2018. Thirty five patients with locally advanced carcinoma involving lower and middle esophagus had concurrent chemoradiotherapy. Induction of concurrent chemoradiotherapy with radiations in which carboplatin and paclitaxel was given weekly. After 6 weeks at the end of irradiation, the clinical response was assessed on CT scan. All patients who had achieved stable, partial and complete clinical response after completion of concurrent chemoradiotherapy (CCRT) underwent surgery within 6-8 weeks. After surgery, pathologist evaluated resected specimen and staging was done on the basis of residual tumor. To grade the response to therapy, the degree of histomorphologic regression classified into four categories as Pathological complete response (pCR), pathological partial response, stable disease as no pathological response and progression of disease. Statistical analysis was performed using SPSS version 23. Chi-square test was applied to assess association between effect modifiers and complete pathological response. &#x0D; Results: Total of 35 patients were included in the study. Mean age of the patients was 42.42±14.16 years. There was female preponderance (57.4%) with male to female ratio of 17:18. Eleven patients (31%) achieved complete clinical response and 2 patients (6%) had stable disease. After surgery, complete pathological response was observed in 21 (60%) patients. However, 10 (28.6%) patients achieved partial pathological response, 1 (2.9%) patient had stable disease and 3 (8.6%) patients showed progression of disease.&#x0D; Conclusion: The achievement of complete pathological response was comparatively higher than partial response among locally advanced EC patients who had neoadjuvant CCRT followed by surgery.