Chemoradiotherapy Research Articles

MR perfusion characteristics of pseudoprogression in brain tumors treated with immunotherapy - a comparative study with chemo-radiation induced pseudoprogression and radiation necrosis.

Pseudoprogression is an atypical imaging pattern of response to immunotherapy in patients with brain tumors. MR perfusion studies in this field are limited. The purpose of our study is to compare the perfusion features between pseudoprogression lesions in malignant gliomas and brain metastases treated with immunotherapy (iPsP) and the pseudoprogression after chemo-radiation therapy and radiation necrosis after radiation treatment (ChR-PsP & RN). We retrospectively reviewed 25 iPsP lesions in 16 brain tumor patients and 48 ChR-PsP & RN lesions in 35 patients. The cerebral blood volume (CBV) of MR dynamic susceptibility contrast (DSC) perfusion weighted imaging (PWI) was analyzed, and the mean and maximal values of the ratio of CBV (rCBVmean and rCBVmax) of iPsPs and ChR-PsP & RNs were calculated and compared between these two groups using the Mann-Whitney U test. A receiver operating characteristic curve analysis was conducted, and the optimal cutoff of perfusion parameters were determined using the area under the curve, sensitivity, and specificity. The medians of rCBVmean and rCBVmax in iPsP group were significantly higher (0.94 and 1.39 respectively) than ChR-PsP & RN group (0.67, p < 0.01 and 1.1, p = 0.01 respectively). The rCBVmean value of 0.69 can differentiate the iPsP from ChR-PsP & RN with the area under the curve of 0.71, sensitivity of 0.72, and specificity of 0.56. These findings may suggest immunotherapy-induced higher perfusion in the iPsP lesions compared to ChR-PsP & RN lesions in primary and metastatic brain tumors.

Contact X-ray Brachytherapy (CXB) as a boost therapy after neoadjuvant (chemo)radiation in high-risk locally advanced rectal cancer.

Radical surgery following neoadjuvant therapy is the standard of care for locally advanced rectal cancer. A Contact X-ray Brachytherapy (CXB) boost can alternatively be used to treat residual disease post neoadjuvant (chemo)radiation, especially in patients who are not suitable for or do not wish to have surgery. Its role has mostly been studied to date in low to intermediate-risk patients. We have now evaluated the utility of CXB-boost in high-risk rectal cancers after their tumours have been significantly downstaged by neoadjuvant (chemo)radiation. Oncological outcomes and treatment tolerability were evaluated in 328 patients based on rectal cancer treatment risk stratification: low/intermediate risk (cT1-3ab, N0-1, M0, no extramural invasion (EMVI), mesorectal fascia (MRF) involvement >1mm) and high-risk (cT3cd-4/N2, M0, MRF≤1mm and/or EMVI positive). With median follow-up of 33(IQR:15-54) months and median age of 73(IQR:62-80) years, no significant differences were found between low/intermediate and high-risk groups in clinical complete response (78% vs 73%, p=0.32), local regrowth (16.6% vs 22.4%, p=0.41), nodal (1.8% vs 5.8%, p=0.051) or regional (1.3% vs 2.9%, p=0.33) relapse, or post-radiation toxicities (p=0.16). However, the high-risk group had a higher distant relapse rate (21.2% vs 10.7%, p=0.01), with no significant differences in 3-year organ preservation (80% vs 87%, p=0.25), 5-year disease-free (DFS) (62% vs 64%, p=0.46), or overall (OS) survivals (67% vs 64%, p=0.88). Longer treatment time, treatment gap >24 weeks between therapies, and administration of a higher than standard CXB dose were newly identified factors that negatively impacted outcomes. High-risk rectal cancer patients treated with CXB-boost had more distant relapses, but comparable locoregional tumour control, organ preservation, DFS and OS to lower-risk patients, with acceptable toxicities. CXB-boost is therefore a viable option for selected high-risk rectal cancer patients. Timely reassessment, prompt referral, and CXB dose optimisation are crucial for improving outcomes.

Comparison of treatment regimens for unresectable stage III epidermal growth factor receptor (EGFR)mutant non-small cell lung cancer.

Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor (EGFR) mutations in PACIFIC study ( evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. We screened the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from January 1, 2000 to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. A total of 1156 patients were identified in 16studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS after the TKI-containing treatments was significantly longer than after the TKI-free treatments (hazard ratio [HR]=0.37, 95% confidence interval [CI],0.20-0.66). The PFS of TKI monotherapy was significantly longer than CRT (HR=0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR=1.78, 95% CI,1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8months, 95% CI=37.2-84.3 months) and the longest PFS (21.5months, 95% CI,15.4-27.5 months) in integrated analysis. For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings the best survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. PROSPERO; https://www.crd.york.ac.uk/PROSPERO/; No. CRD42022298490.

Nutritional Gender-Specific Differences in Head and Neck Cancer Patients Treated with (Chemo)Radiotherapy: Results from a Prospective Trial.

Background/Objectives: This analysis aims to evaluate gender-specific differences in nutritional status, body weight changes, and their impact on overall survival (OS) in head and neck cancer (HNC) patients undergoing (chemo)radiotherapy (CRT). Methods: Between 2018 and 2020, 61 HNC (17 female and 44 male) patients were prospectively recruited to receive curative (chemo)radiotherapy. Nutritional assessments included dietary questionnaire screenings and records, anthropometric methods (body mass index, BMI, body composition via bioelectrical impedance analysis (BIA)), and the determination of biomarkers like albumin and CRP. Assessments were conducted before, during, and after (chemo)radiotherapy. Results: Gender differences were observed at baseline in Karnofsky performance status (p = 0.01), daily calorie intake (p = 0.04), phase angle (PA) (p = 0.003), and fat-free mass index (FFMI) (p < 0.001). During CRT, males showed a larger increase in calorie deficit (p < 0.001) and greater reductions in BMI, FFMI, and PA compared to females. Malnutrition risk (MUST score) increased significantly in males (p = 0.008) but not in females. Albumin and total protein declined in both genders, with a more pronounced drop in albumin for females. Survival analysis revealed that, for males, several factors, including baseline calorie deficit, BMI, PA, and FFMI, were linked to survival. For females, only albumin at therapy end was significantly associated with survival (p < 0.001). In multivariable analysis, baseline PA remained a significant predictor of survival for males (p = 0.026). Conclusions: Our findings suggest distinct gender differences in the nutritional and biochemical responses of HNC patients undergoing CRT, indicating the importance of tailored, gender-specific nutritional support during treatment.

A randomized phase 3 trial of total neoadjuvant therapy (induction chemotherapy, neoadjuvant chemoradiation, neoadjuvant chemotherapy, and surgery) vs. standard long-term chemoradiation therapy (neoadjuvant chemoradiation, surgery, and adjuvant chemotherapy) in locally advanced rectal cancer

PurposeThe management of rectal adenocarcinoma has evolved during the last decade, shifting from a conventional neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy in all cases to a total neoadjuvant approach, especially in locally advanced tumors when a sphincter-sparing surgery has been planned. However, the exact indications and the neoadjuvant regimen with the highest response remain unresolved. We aimed to assess whether administering neoadjuvant chemotherapy before and after preoperative chemoradiotherapy could increase the pathological complete response (pCR) rates.MethodsWe conducted a phase 3, multicenter, randomized trial at four hospitals in Iran. Adult patients with a newly diagnosed, biopsy-proven, locally advanced non-metastatic rectal adenocarcinoma with an ECOG performance status of 0–2 were randomly assigned (2:2) to either the total neoadjuvant treatment (TNT) or the standard-of-care groups using a block randomized design. Investigators and participants were not masked to treatment allocation and groups. The TNT group received neoadjuvant chemotherapy with FOLFOX6 (intravenous 85 mg/m2 oxaliplatin and 400 mg/m2 leucovorin, followed by intravenous 400 mg/m2 fluorouracil bolus and then continuous infusion at a dose of 2,400 mg/m2 over 46 h every 14 days for four cycles before and four cycles after chemoradiotherapy), chemoradiotherapy (50.4 Gy during 28 fractions and 800 mg/m2 concurrent oral capecitabine twice daily 5 days per week), and total mesorectal excision. The standard-of-care group received neoadjuvant chemoradiotherapy, total mesorectal excision, and adjuvant chemotherapy (eight cycles). The primary endpoint was the pathological complete response. Safety analyses were conducted on treated patients.ResultsOverall, 25 and 27 patients were enrolled in the TNT and standard-of-care groups, respectively. Both groups were similar in terms of gender, age, and tumor differentiation. The tumors in the standard-of-care group were significantly located closer to the anal verge compared with those in the TNT group (9.4 ± 3.7 cm in TNT vs. 6.8 ± 4 cm in standard, p = 0.02). A pCR was reached in 48% (12/25) and 25.9% (7/27) of patients in the TNT and standard-of-care groups, respectively (p = 0.4). The R0 resection rates were identical between the two groups (92% vs. 88.9%, p = 0.3). Moreover, the toxicity rates were similar between the two groups.ConclusionOur results showed that TNT is a safe and feasible treatment approach in patients with rectal cancer and may improve the overall pCR rate compared with standard treatment.Clinical trial registrationhttps://irct.behdasht.gov.ir/trial/65666, identifier IRCT20220723055527N1.

Comparison of outcomes between surgery and chemoradiotherapy after endoscopic resection for pT1a-MM with lymphovascular invasion or pT1b esophageal squamous cell carcinoma: Japanese multicenter propensity score-matched study.

Lymphovascular invasion (LVI) or pT1b is noncurative after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC), andtherefore surgery or chemoradiotherapy (CRT) is recommended. However, there has been debate regarding which treatment has better outcomes and whether individual risks should be considered. This was a multicenter, retrospective study conducted at 65 hospitals in Japan. The inclusion criteria were patients with ESCC who underwent ER between January 2006 and December 2015, with pT1a-muscularis mucosa (MM) with LVI or pT1b, with negative vertical margins, cN0M0, and who underwent surgery or CRT. A 1:1 propensity score-matched analysis was performed between two groups. The primary and secondary end points were overall survival (OS) and relapse-free survival (RFS). OS and RFS were also compared between two subgroups: low risk (pT1a-MM with LVI and pT1b without LVI) and high risk (pT1b with LVI) for metastatic recurrence. Among 472 patients, 160 patients were selected from each group. The OS and RFS did not differ between surgery and CRT groups (hazard ratio, 0.887; P = .635 and hazard ratio, 1.036; P = .876, respectively). Subgroup analysis showed that CRT had a better prognosis in the low-risk group, and conversely, surgery had a better prognosis in the high-risk group. But these were not significant. The high-risk CRT group had a significant worse prognosis than the low-risk CRT group. In patients with noncurative ER for ESCC, surgery and CRT showed no difference in long-term outcomes. Indications for CRT in the high-risk group need further investigation because of poor prognosis.

Short-term and long-term oncological outcomes of chemoradiotherapy for rectal cancer patients with or without oxaliplatin: a propensity score-matched retrospective analysis

Background/AimCurrent approaches for locally advanced rectal cancer (LARC) typically recommend neoadjuvant chemoradiotherapy (nCRT) with 5-fluorouracil (5FU) or its oral analogs followed by surgery as the standard of care. However, the question of whether intensifying concurrent chemotherapy by adding oxaliplatin to the 5FU-based backbone can yield better outcomes remains unresolved. This study aimed to investigate the benefits of incorporating oxaliplatin into fluoropyrimidine-based chemoradiotherapy (CRT) to increase locoregional control and survival.MethodsAmong 290 patients with LARC admitted to the Iran Cancer Institute’s radiation oncology department between January 2008 and December 2019, 29 received CAPEOX (capecitabine 625 mg/m²/bid on RT days and weekly oxaliplatin 50 mg/m²), whereas 293 received capecitabine (825 mg/m² twice daily or rarely 5FU in the first 4 days and last week of radiotherapy (RT)). Variables potentially affecting treatment outcomes were used for propensity score matching. Kaplan‒Meier and log-rank tests were employed for overall survival (OS) and disease-free survival (DFS) analyses and were adjusted with propensity score matching.ResultsData from 29 patients who received CAPEOX and 216 patients who received capecitabine were analyzed after propensity score matching without replacement. After propensity score matching, in the multivariate analysis, CAPEOX significantly increased the likelihood of achieving a pathologic complete response (pCR) by 4.38 times (CI: 1.90–10.08, p value < 0.001). However, CAPEOX did not demonstrate any statistically significant predictive value for DFS (P = 0.500) or OS (P = 0.449).ConclusionThe addition of oxaliplatin resulted in a significantly higher rate of pCR without any translation into long-term survival outcomes.

Tumor budding is an independent adverse prognostic factor of pancreatic ductal adenocarcinoma patients treated by resection after preoperative chemoradiotherapy.

To examine the significance of tumor budding as a prognostic factor of resected pancreatic ductal adenocarcinoma (PDAC) specimens after preoperative chemoradiotherapy (CRT). Among 162 PDAC patients who underwent pancreatectomy after gemcitabine and S1-based CRT from 2012 to 2019, 131 were evaluated for tumor budding. Tumor buds were counted at the invasive front, where the degree of budding was the greatest (hematoxylin and eosin staining, ×20 magnification). Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were compared between the patients without tumor budding (non-TB group) and those with tumor buddings (TB group). Multivariate Cox proportional hazards analysis was conducted to examine the significance of tumor budding as a prognostic factor. OS, DSS, and RFS (median survival time) of the non-TB group were significantly longer than those of the TB group (OS: 50.7 vs. 27.5 months, P = 0.014. DSS: 63.3 vs. 33.0 months, P = 0.014. RFS: 20.3 vs. 11.3 months, P = 0.028). Multivariate analysis identified adjuvant chemotherapy (P = 0.003) as a favorable prognostic factor of OS and tumor budding (P = 0.023) as an adverse prognostic factor of DSS. This study revealed that the presence of tumor budding was an independent adverse prognostic factor in PDAC patients resected after gemcitabine and S1-based CRT.

Comparison between The Efficacy of Concurrent Chemo-Radiation with Gemcitabine Followed by Intracavitary Radiotherapy in Patients with Locally Advanced Cervical Carcinoma

Introduction: Commonest threatening cancer in our Asian round is Cervical cancer. Currently, platinum-based concurrent chemo-radiation therapy is the standard of care for locally advanced cervical cancer but treatment results are disappointing, particularly for women with bulky tumors. To improve this result, several non-platinum-based agents with concurrent chemo-radiation have been evolved. Material and Methods: This was a quasi-experimental study, where 33 patients with untreated invasive squamous cell carcinoma of the cervix of stage IIB to stage IVA were enrolled in the study from the Radiation Oncology Department of Rajshahi Medical College Hospital from April 2019 to March 2020. Duration of the study was 2 years. All patients received 150 mg/m² of Gemcitabine weekly along with external beam radiation therapy (EBRT). EBRT dose was 50 Gy in 25 daily fractions followed by intracavitary radiotherapy (ICRT) of 21 Gy in 3 fractions. Results: The mean patient age was 45.4 years. Most patients were in stage IIB (59.1%) with moderately differentiated tumors (62.1%). After three months of treatment, 81.8% showed complete response, 12.1% partial response, and 6.1% disease progression. Grade 2 and 3 hematological toxicities were common, including anemia (60.6% grade 2; 24.2% grade 3) and neutropenia (24.2% grade 2; 6.1% grade 3). Other side effects included diarrhea (42.4%), proctitis (36.4%), skin toxicity (45.5%), mild renal toxicity (3%), and grade 2 cystitis (9.1%). Conclusion: Gemcitabine-based concurrent chemo-radiation is a potential alternative for patients contraindicated for Cisplatin. However, larger randomized studies are needed to confirm its safety and efficacy.

Defining Optimal Nodal Dose for Stage IIIC Cervical Cancer: An Institutional Audit of Patients Treated with Simultaneous Integrated Nodal Boost

ObjectiveTo assess radiation dose-response relationship for individual lymph nodes in patients with stage IIIC cervical cancer who are treated with simultaneous integrated boost (SIB).MethodsThis is a retrospective study in which patients with stage IIIC cervical cancer treated with (chemo)radiation who received simultaneous integrated nodal boost (SIB) and brachytherapy were evaluated with the primary aim of determining in-field nodal control. Secondary aims included estimation of local control (LC), disease free survival (DFS) and adverse events. Univariate analysis and multivariate analysis was performed for factors impacting nodal control, LC and DFS.ResultsOne hundred and fifty-one (151) nodes in 65 patients were included. The median number of lymph nodes and nodal volume was 2 (1–6) and 3.4 cc (1.8–6.8 cc) respectively. Median SIB dose was 55Gy/25# (53.7–55.0 Gy). At a median follow-up of 43 months the in-field nodal control was 99.3% (1/151). The 5-year LC, DFS and regional nodal control was 88.7, 66 and 85.6% respectively. The 5-year DFS for FIGO stage IIIC1 was 67.7% versus 43.5% for stage IIIC2 (p = 0.03) and lymph node volume >3cc was associated with reduced 5-year DFS (80.8% vs. 55%, p = 0.03) on univariate analysis. No factor was statistically significant on multivariate analysis. A vast majority of lymph node recurrences were observed in elective nodal regions outside the true pelvis that received lower contribution from brachytherapy.ConclusionNodal SIB doses of up to 55Gy/25#/ 5 weeks administered during chemoradiation are associated with 99.3% 5-year infield nodal control. A vast majority of nodal recurrences were observed in elective volumes that received a lower contribution from brachytherapy.

Identification of a Suitable Subgroup for Radiation Dose Escalation in Definitive Concurrent Chemoradiation Therapy for Nonmetastatic Esophageal Squamous Cell Carcinoma.

Dose escalation may only be suitable for some patients with esophageal cancer (EC) undergoing concurrent chemoradiotherapy (CCRT). This study aimed to identify specific subgroups of patients for whom dose escalation was most beneficial. Between January 2008 and December 2022, 187 patients with EC underwent CCRT; 94 patients received high-dose (HD) radiotherapy (RT; >64.8 Gy), and 93 patients received low-dose (LD) RT. We developed a model on the basis of clinical and radiomic features to compare the predicted survival probabilities of patients with EC receiving HD- and LD-RT. Patients suitable for HD-RT could be identified. We validated our findings of a suitable HD subgroup by evaluating the actual overall survival (OS) across different subgroups in the testing set. Our model comprised HD and LD submodels, each predicting patient survival under their respective RT doses. The HD and LD submodels achieved concordance indexes of 0.78 and 0.75 in their respective testing sets. The average areas under the receiver operating characteristic curve over years 1-3 were 0.890 and 0.807 in the HD and LD testing sets, respectively. By comparing patients' predicted survival under HD- and LD-RT in the model, we classified the patients in the testing set into the HD-suitable (HDS) subgroup and the HD-unsuitable subgroup. In the subgroup analysis, HD-RT led to a better OS benefit for the identified HDS subgroup compared with LD-RT (P = .014). Among the HD-treated patients, the HDS subgroup showed better OS than did patients identified as unsuitable (P < .001). We identified a suitable subgroup of patients with EC who might benefit from HD-RT. This model could aid clinicians in prescribing RT doses.

Prognostic factors associated with worse outcomes following chemoradiation therapy in patients with anal carcinoma.

Chemoradiation therapy (CRT) is considered as the first line of treatment for patients with squamous cell carcinoma of the anal canal. Following initial CRT, patients who present with either persistent or locally recurrent disease are treated by surgical intervention. The aim of our study is to determine the prognostic factors associated with failure of CRT and overall mortality in patients with anal squamous cell carcinoma (SCC). We performed a 14-year analysis (2004-2017) of the National Cancer Database and included patients diagnosed with non-metastatic SCC of the anal canal who underwent CRT. Baseline patient characteristics including demographics, comorbidities and tumour characteristics were analysed. Outcome measures were needed for operative intervention after 4 months of initiation of CRT (failure of CRT) and 5-year overall mortality. Multivariate logistic regression analysis identified prognostic factors independently associated with failure of CRT. We included a total of 37 615 patients with anal SCC who received CRT. Predictors of operative intervention included male sex, higher Deyo-Charlson Comorbidity Index (DCCI) and higher primary tumour stage. The 5-year overall survival rate was 77.6%, and 2.4% of patients failed CRT, defined as requiring and undergoing surgical intervention within 4 months post-initiation of CRT. Median follow-up time was 47 (95% CI 24-84) months. Independent predictors of overall mortality within the first 5 years of diagnosis were increased age, male sex, Black race, non-insured status, higher DCCI, higher primary tumour grade, and higher primary tumour and lymph node stage. The 5-year survival rate was significantly lower in patients who underwent operative intervention compared to those who received CRT alone (57.4% vs. 78.1%; P < 0.01). Our study showed that male sex, younger age, DCCI of 1 and 3, and increased tumour size were predictive of CRT failure among patients with anal SCC. Increased age, male sex, Black race, non-insured status, increased DCCI, and more aggressive tumour characteristics were associated with increased 5-year overall mortality. More importantly, patients who failed CRT had worse 5-year overall survival. Our findings support increased emphasis on intensive surveillance for these high-risk patient cohorts.

Analysis of results of radiotherapy for oropharyngeal cancer.

Smoking and alcohol consumption remain the two most important risk factors for the development of oropharyngeal tumours, but there is an increasing number of younger patients (age <50 years) with human papillomavirus (HPV) association origin, also known as positivity. The role of radiotherapy (RT) in the treatment of this disease is paramount. To describe the radiotherapy results for oropharyngeal tumours and to search for prognostic parameters that influence the response of these malignant lesions to radio-chemotherapy. 95 patients underwent definitive radio- or radio-chemotherapy (RCT) for histologically squamous cell, oropharyngeal carcinoma at our Institute between 1January 2019 and 31 December 2020, of which 51 (54%) received the latter. The mean age was 61.9 years (37-82 years) and the male-female ratio was 69:26. The average total dose was 69 Gy (range: 54-70 Gy). The 5-year local control (LC), cancer-specific survival (CCS), and overall survival (OS) calculated by the Kaplan-Meier method were 71, 69, and 58%, respectively. Forty-four cases (46%) were confirmed tohave HPV involvement. HPV positive (+) tumours showed significantly better behaviour compared to HPV negative (-) cases in LC, CCS and OS. Smoking had a significant negative effect on cure rates: LC, CCS and OS were better in non-smokers. A significant negative effect of smoking on survival was alsoobserved in HPV-associated cases. For HPV- lesions, RCT had a stronger effect on LC than RT alone(64 vs43%, P = 0.03). HPV-associated malignancies show better survival outcomes toradio ± chemotherapy than their HPV- counterparts. In all cases, smoking worsens the response to treatment. For HPV- tumours, chemotherapy with radiation, compared to irradiation alone, has a more significant effect on survival outcomes, whereas for HPV+ tumours this effect is less pronounced.

Induction chemotherapy plus chemoradiotherapy in esophageal cancer: long-term results and exploratory analyses of a randomized controlled trial.

Previous results of our trial demonstrated that the addition of induction chemotherapy (IC) prior to definitive chemoradiotherapy (CRT) failed to significantly improve the response rate or 3-year survival in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Here, we report long-term results and exploratory analyses to further evaluate the therapeutic value of IC. Patients with previously untreated, unresectable, stage II-IVA ESCC were randomly assigned to receive IC followed by CRT or CRT alone. The relationship between tumor response to IC and long-term survival was analyzed. Baseline tumor biopsies were collected for RNA-Seq to identify patients who may benefit from IC. Eligible patients were randomized to either the IC + CRT group (n = 55) or the CRT group (n = 55). With a median follow-up of 74.9 months, the 5-year overall survival rate was 31.8% in the IC + CRT group and 29.1% in the CRT group (P =.675; HR, 0.91; 95% CI, 0.58-1.43). Similarly, no significant differences were identified in 5-year progression-free survival between groups (30.5% vs 25.5%, P =.508; HR, 0.86; 95% CI, 0.56-1.34). Patients who responded to IC had significantly better survival than nonresponders. A risk-score model incorporating 6 key genes to predict IC efficacy was also constructed. Compared with definitive CRT alone, the addition of IC before CRT still failed to demonstrate superior survival in patients with unselected ESCC, based on long-term follow-up. However, because IC responders were associated with more favorable survival, potential molecular biomarkers were identified for selection of benefit population from IC. NCT02403531.

METHODOLOGICAL APPROACHES TO STANDARDIZATION OF COMPLEX PHYTOADAPTOGENS FOR PREVENTIVE ONCOLOGY

Preventive oncology can solve such problems as preventing the appearance of tumors, relapses after primary treatment, and complications after chemo-radiation therapy. The prospects for use of phytoadaptogens (Panax ginseng, Rhodiola Rosea, Eleutherococcus senticosus etc.), which pleiotropically influence the body along the homeostasis axis (neuro-endocrine-immune systems), are obvious.

Comparison of intravoxel incoherent motion and diffusion kurtosis imaging and 18- FDG PET/CT in response assessment in rectosigmoid carcinoma.

To evaluate the performance of intravoxel incoherent motion and diffusion kurtosis imaging (IVIM- DKI) in response assessment of rectosigmoid carcinoma to chemo-radiotherapy (CRT) and compare with 18-FDG PET/CT parameters. A total of 30 patients of recto-sigmoid cancer on CRT underwent baseline staging and follow-up with IVIM - DKI. Out of this cohort, 20 patients underwent 18-FDG PET/CT. IVIM- DKI MRI and PET/CT parameters were noted from both pre and post-chemoradiotherapy (done at 6 weeks after completion) scans. Quantitative IVIM-DKI parameters, viz. apparent (ADC) and molecular (D) diffusion coefficient, perfusion coefficient (f), and kurtosis (K) were measured from non-necrotic areas and semi-quantitative PET parameters including SUV max, SUV ratio, metabolic tumor volume (MTV), total lesion glycolysis (TLG) were also measured. All these parameters correlated with the patient's response keeping RECIST 1.1 criteria as reference standard. A statistically significant increase in D and ADC with a significant decline in K was noted after therapy in the entire cohort. These changes were observed in both responders as well as non-responders. No significant differences were observed in the percentage changes of these parameters post therapy amongst both groups. Among 20 patients with follow-up PET/CT imaging, a significant decline in all parameters of primary lesion was seen post-therapy. Responders (n = 12) showed a significant decline in MTV and TLG from baseline after therapy, whereas non-responders did not show any such decline. Change in TLG (ɗ TLG), followed by ɗ MTV had the strongest correlation with a positive response. A ɗ TLG value of ≥ 54.19 carried a 79% sensitivity and 83% specificity in differentiating responders from non responders. 18-FDG PET/CT is a more accurate single modality for assessing both response and tumor burden post therapy, while ADC and D from IVIM MRI are useful adjuncts to response assessment.

Contrast-Enhanced Computed Tomography (CT) With Concordant Sonography as Sufficient Early Detection Tools for Recurrent and Persistent Cervical Metastases After (Chemo)radiotherapy (CRT).

Most challenging treatment needs are in recurrent or persisting head and neck squamous cell carcinoma (HNSCC) patients after (((chemo-)radiotherapy) (C)RT). This 10-year retrospective study included 100 patients, who initially received (C)RT followed by neck dissection (ND). The results of computed tomography (CT) and sonography were evaluated for residual/recurrent cervical lymph nodes and compared to the histopathology. On this basis we calculate the sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV). A total of 144 ND specimens were analyzed. The combination of CT and sonography (n = 103) reached values 97% sensitivity, 71% specificity, 98% NPV, 66% PPV, and 81% overall accuracy. For patients who received as primary treatment CRT the values for the combined imaging were: 100.0%, 73.5%, 100.0%, 66.7% and 82.7% respectively. Our study demonstrates that the combined use of CT and sonography reliably detects lymph node metastases, particularly in patients previously treated with CRT, even after a long time after treatment.

Chemoradiotherapy and Subsequent Immunochemotherapy as Conversion Therapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Phase II NEXUS-1 Trial.

This phase II trial investigated the safety and efficacy of chemoradiotherapy (CRT) followed by immunochemotherapy (iCT) and surgery in unresectable locally advanced esophageal squamous cell carcinoma (ESCC). Patients with unresectable locally advanced ESCC received radiotherapy (50 Gy/25f, 5 days/week) and nab-paclitaxel (100 mg on day 1/week) plus cisplatin (25 mg/m2 on day 1/week) for 5 weeks, followed by tislelizumab (200 mg on day 1/cycle) plus chemotherapy (nab-paclitaxel 150 mg/m2 and cisplatin 75 mg/m2 on day 2/cycle) for two 21-day cycles. Patients who converted to resectable underwent surgery 2 to 4 weeks afterward. The primary endpoint was a 1-year progression-free survival (PFS) rate. Thirty patients were enrolled and underwent CRT (median follow-up: 21 months), of whom 24 received iCT. Twenty (66.7%) patients achieved resectability (R0: 95.2%; pathologic complete response: 65.0%; major pathologic response: 90.0%). One-year PFS and overall survival (OS) rates were 79.4% and 89.6%, respectively. The R0 resection group exhibited longer PFS (median, not reached vs. 8.4 months; HR = 0.28; 95% confidence interval, 0.08-0.84; P = 0.02) and OS (median, not reached vs. 19.2 months; HR = 0.18; 95% confidence interval, 0.04-0.73; P < 0.01) than the nonsurgery group. Grade 3 to 4 adverse events were observed in 11 (11/30, 36.7%) patients, and immune-related pneumonitis was observed in 5 (5/24, 20.8%) patients. Post-CRT minimal residual disease before surgery was associated with unfavorable PFS and OS. Our study met the primary endpoint. Conversion CRT and subsequent iCT followed by surgery was a promising treatment strategy for unresectable locally advanced ESCC.

The impact of Prophylactic cranial irradiation on the prognosis of patients with limited-stage small cell lung cancer in the MRI era

PurposesTo evaluate the impact of prophylactic cranial irradiation (PCI) on the prognosis of patients with limited-stage small cell lung cancer (SCLC) in the era of MRI surveillance.MethodsLimited-stage SCLC patients with complete remission (CR) or partial remission (PR) of tumor after definitive chemo-radiotherapy (CRT) were retrospectively analyzed. Survival data were calculated by Kaplan-Meier methods, Cox proportional hazards model was applied for multivariate prognostic analysis.ResultsBetween June 2002 and January 2017, 620 patients with limited-stage SCLC were accrued in our study. After CRT, 228 (36.8%) patients achieved CR, of whom, 29 patients did not receive PCI, among the rest 199 patients, 172 (86.4%) received brain MRI to exclude brain metastasis (BM) before PCI. With a median follow-up time of 25.6 months, the cumulative BM rate was 17.1% and 37.9% in patients who received or did not receive PCI (P = 0.011). The median survival time was 30.2 months and 30.5 months, respectively and the 1 -, 3 -, 5-year survival rates were 93.7%, 42.9%, 35.8% and 83.4%, 46.5%, 41.9%, respectively (P = 0.98). Multivariate analysis indicated that baseline KPS ≥ 90 was a favorable independent prognostic factor for OS in CR patients (HR: 0.33, 95% CI: 0.23–0.46, P = 0.000). After CRT, 392 (63.2%) patients achieved PR, 53 cases did not receive PCI and 310 (91.4%) of the remaining 339 patients received brain MRI before PCI. With a median follow-up time of 15.5 months, the cumulative brain metastasis rate was 12.7% and 46.2% respectively (P = 0.000). The median survival time was 25.7 months and 18.6 months, respectively. The 1 -, 3 -, and 5-year survival rates were 87.6%, 40.2%, 29.2% and 75.7%, 16.7%, 10.3% (P = 0.000). Baseline KPS ≥ 90 (HR: 0.32, 95% CI: 0.25–0.41, P = 0.000) and PCI (HR: 0.57, 95% CI: 0.41–0.79, P = 0.001) were favorable prognostic factors for OS in PR patients.ConclusionsIn this study, PCI significantly reduced the incidence of BM in patients with limited-stage SCLC who were evaluated as CR and PR after CRT, but it has no significantly positive impact on overall survival in CR patients. Further prospective randomized studies were warranted.

Effect of External Beam Radiation Therapy and Brachytherapy on Circulating Myeloid-Derived Suppressor Cell Populations in Patients Treated Definitively for Cervical Cancer

PurposeThe immunosuppressive function of myeloid derived suppressor cells (MDSCs) has been implicated in the regulation of immune responses against cancer and is associated with poor prognosis. Radiation treatment is known to alter immune cell populations within the tumor, however, whether this results in recruitment of immunosuppressive MDSC populations is not well understood. Here we evaluate the response of circulating MDSC populations in patients treated per standard of care cisplatin chemoradiation therapy (CRT) for locally invasive cervical cancer. Methods and MaterialsNewly diagnosed, treatment naïve patients with locally advanced cervical cancer were enrolled. Blood samples were collected from patients prior to starting CRT (T0), after external beam radiation therapy (EBRT) (T1), and after high-dose rate brachytherapy (T2). Samples from each timepoint were processed and prevalence of MDSC subsets were determined by flow cytometry. MDSC populations were identified by Live/Dead-CD11b+CD33+HLA-DR- staining. MDSC subsets were further subdivided into granulocytic (g-, CD15+CD14-), monocytic (m-, CD15-CD14+), or early-MDSCs (e-, CD15-CD14-). ResultsMost patients in our study were Caucasian non-smokers with HPV-associated squamous cell carcinoma of the cervix. We saw a trend for increased MDSC frequency in patients with more advanced stage disease at the time of initiating treatment. MDSCs increase in response to CRT and peak after brachytherapy (T2). In particular, the g-MDSC subset which increases 6.44x relative to baseline. There was no correlation between MDSC expansion and response to therapy. ConclusionOur study confirms other reports that circulating MDSCs in patients with cervical cancer increase in response to CRT and are associated with more advanced stage. Additionally, we show that MDSC expansion is driven by the g-MDSC subset. We did not see any correlation between MDSC expansion and treatment response, though this may be due to the limited sample size for this study