Can rectal MRI and endorectal ultrasound accurately predict the complete response to neoadjuvant immunotherapy for rectal cancer?

Background: Standardized assessments of clinical complete response (cCR) to neoadjuvant chemoradiotherapy (nCRT) for rectal cancer have been established, but their utility and accuracy remain unclear. This study aimed to evaluate the clinical diagnostic value of rectal magnetic resonance imaging (MRI) and endorectal ultrasonography (ERUS) for the determination of cCRs after neoadjuvant immunotherapy and to investigate the concordance between cCR and pathological complete response (pCR). Methods: Ninety-four patients with rectal cancer treated with neoadjuvant radiotherapy with or without immunotherapy were included. The sensitivity, specificity, and accuracy of each evaluation method were calculated. Results: Combined MRI and ERUS assessments found cCR in seven of the 94 patients in our cohort. In the non-immunotherapy group, the sensitivity, specificity, and accuracy of MRI for diagnosing cCR were 50.0%, 85.2%, and 77.1%, respectively, whereas those of ERUS were 50.0%, 92.6%, and 82.9%, respectively; those of combined MRI and ERUS were 25.0%, 96.3%, and 87.5%, respectively. In the immunotherapy group, the sensitivity, specificity, and accuracy with which MRI identified CR were 51.7%, 76.7%, and 64.4%, respectively; those of ERUS were 13.8%, 90.0%, and 52.5%, respectively, and those of combined MRI and ERUS were 10.3%, 96.7%, and 54.2%, respectively. We also found that 32 of 37 patients with pCR did not meet the cCR evaluation criteria. Of these pCR patients, 78.4% (29/37) received immunotherapy. In the entire cohort, there were five pCRs among the seven cCRs. Of the four cCRs that occurred in the immunotherapy group, three were pCRs. Conclusions: Rectal MRI and/or ERUS did not provide sufficiently accurate assessments of cCR in patients with rectal cancer receiving neoadjuvant therapy, especially immunotherapy, and cCR did not predict pCR.

Significant response to pembrolizumab plus lenvatinib in Epstein-Barr-virus-associated intrahepatic cholangiocarcinoma: a case report.

BACKGROUND: The prognosis for advanced intrahepatic cholangiocarcinoma (iCCA) is poor, and there remains an urgent need to develop efficient systemic therapy. The efficacy of Pembrolizumab immunotherapy combined with lenvatinibin in iCCA is still unclear. The role of Epstein-Barr-virus (EBV) as a biomarker in iCCA for response to immunotherapy needs further exploration. CASE PRESENTATION: We report a case of a 60-year-old female with EBV-associated advanced iCCA (EBVaiCCA) who progressed after first-line therapy. She accomplished an available response to the combination therapy of pembrolizumab with lenvatinib, with overall survival of 20 months. CONCLUSIONS: As far as we know, this is the first case report about the application of Pembrolizumab with lenvatinib for EBVaiCCA patients. This case indicates that the combination of immunotherapy and antiangiogenic therapy provides a glimmer of hope for advanced EBVaiCCA patients.

Efficacy and safety of radiotherapy combined with anti-angiogenic therapy and immune checkpoint inhibitors in MSS/pMMR metastatic colorectal cancer.

PURPOSE: Several studies have demonstrated the effectiveness of anti-angiogenic drugs in combination with immune checkpoint inhibitors (ICIs) in patients with microsatellite stable (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC). However, whether combination radiotherapy (RT) can further improve the prognosis of mCRC patients after second-line treatment remains to be explored. METHODS: Retrospective analysis of data from mCRC patients who received anti-angiogenic targeted therapy (TT) and immunotherapy (IT) with or without RT after the failure of standard therapy. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety were evaluated. RESULTS: A total of 82 patients who received TT + IT were analyzed. For RT group (n = 42) versus NRT group (n = 40), ORR was 21.4% (9/42) versus 5.0% (2/40); DCR was 83.8% (35/42) versus 65.0% (26/40). Compared with NRT group, RT improved PFS (median: 5.0 vs. 3.6 months; p = 0.04) and OS (median: 15.2 vs. 7.2 months; p = 0.01). In addition, in the population receiving RT, the PFS of RT sequential/simultaneous TT + IT was superior to TT + IT sequential RT (median: 7.1 vs. 6.2 vs. 3.5 months, p = 0.004). Multivariate analysis suggested RT was an independent prognostic factor for PFS and OS. No treatment-related deaths were reported. CONCLUSIONS: Compared with TT + IT, RT combined with TT + IT improved survival outcomes in MSS/pMMR mCRC patients, with manageable toxicity. RT sequential/simultaneous TT + IT treatment is expected to be the optimal strategy for MSS/PMMR mCRC.

Pretreatment high cholesterol and low neutrophils predict complete pathological response after neoadjuvant short­course radiotherapy followed by chemotherapy and immunotherapy in locally advanced rectal cancer.

The present study was aimed at looking for hematological indicators that could predict pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC) treated with short-course radiotherapy (SCRT) followed by chemotherapy and immunotherapy. A total of 171 patients were enrolled in this observational retrospective study. Pretreatment values of albumin, total cholesterol, lactate dehydrogenase, neutrophil, platelet and lymphocytes were available. Univariate and multivariate logistics analyses were used to determine the prognostic factor for pCR. SCRT followed by chemotherapy and immunotherapy was demonstrated to double the pCR rate (50.5%) compared with long-course chemoradiotherapy. For the former group, baseline high platelet to lymphocyte ratio (P=0.047), high cholesterol (P=0.026) and low neutrophils (P=0.012) level were associated with high pCR rate and baseline high cholesterol (P=0.016) and low neutrophils (P=0.020) level were the independent prognostic factors for pCR. In conclusion, pretreatment high cholesterol and low neutrophils were the independent prognostic predictors of pCR in patients with LARC treated with SCRT followed by chemotherapy and immunotherapy. Clinical trial no. NCT04928807, June 16, 2021.

Comprehensive Treatment Uncertainty Analysis and PTV Margin Estimation for Fiducial Tracking in Robotic Liver Stereotactic Body Radiation Therapy.

OBJECTIVE: This study aims to quantify the uncertainties of CyberKnife Synchrony fiducial tracking for liver stereotactic body radiation therapy (SBRT) cases, and evaluate the required planning target volume (PTV) margins. METHODS: A total of 11 liver tumor patients with a total of 57 fractions, who underwent SBRT with synchronous fiducial tracking, were enrolled for the present study. The correlation/prediction model error, geometric error, and beam targeting error were quantified to determine the patient-level and fraction-level individual composite treatment uncertainties. The composite uncertainties and multiple margin recipes were compared for scenarios with and without rotation correction during treatment. RESULTS: The correlation model error-related uncertainty was 4.3±1.8, 1.4±0.5 and 1.8±0.7 mm in the superior-inferior (SI), left-right, and anterior-posterior directions, respectively. These were the primary contributors among all uncertainty sources. The geometric error significantly increased for treatments without rotation correction. The fraction-level composite uncertainties had a long tail distribution. Furthermore, the generally used 5-mm isotropic margin covered all uncertainties in the left-right and anterior-posterior directions, and only 75% of uncertainties in the SI direction. In order to cover 90% of uncertainties in the SI direction, an 8-mm margin would be needed. For scenarios without rotation correction, additional safety margins should be added, especially in the superior-inferior and anterior-posterior directions. CONCLUSION: The present study revealed that the correlation model error contributes to most of the uncertainties in the results. Most patients/fractions can be covered by a 5-mm margin. Patients with large treatment uncertainties might need a patient-specific margin.

'FLARE' of tumor marker in advanced gastric cancer treated with first-line systemic therapy.

Background: Transient tumor marker elevations caused by chemotherapy were defined as 'Flare' and have been demonstrated in some solid tumors. In clinical practice, we observed that some patients were accompanied by elevated tumor markers during treatment, but subsequent imaging proved that the treatment they received was effective. Objectives: We aimed to study the Flare and the prognosis in advanced gastric cancer. Design: This is an observational retrospective study. A total of 167 patients were enrolled in this study. Carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9 and CA125 values were obtained before the first, second, third, fourth, fifth and sixth cycles of treatment, respectively. Methods: Imaging for the first efficacy assessment was reviewed according to the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) criteria. Kaplan-Meier analyses and log-rank tests were performed for overall survival (OS) analyses. Univariate and multivariate Cox analyses were used to determine the prognostic factor for OS and progression-free survival (PFS). Results: 37.1% of patients were accompanied with at least one tumor marker Flare during the course of treatment. The median time to tumor marker peak was 24-30 days and the Flare duration lasted 49-53 days. Patients with tumor markers Flare had a worse OS. Flare may be associated with the use of 5-fluorouracil. Baseline CEA and CA125 levels were the independent prognostic factors for OS and baseline CA125 level was the independent prognostic factor for PFS. Conclusion: Initial elevation of tumor markers during treatment is not an indication of tumor progression. Patients with tumor markers 'Flare' may had a worse OS.

A dynamic predictive nomogram of long-term survival in primary gastric lymphoma: a retrospective study.

BACKGROUND: Primary gastric lymphoma (PGL) is the most common extranodal non-Hodgkin lymphoma (NHL). Due to the rarity of the disease, it is important to create a predictive model that provides treatment and prognosis for patients with PGL and physicians. METHODS: A total of 8898 and 127 patients diagnosed with PGL were obtained from the SEER database and from our Cancer Center as training and validation cohorts, respectively. Univariate and multivariate Cox proportional hazards models were used to investigate independent risk factors for the construction of predictive survival nomograms, and a web nomogram was developed for the dynamic prediction of survival of patients with PGL. The concordance index (C-index), calibration plot, and receiver operating characteristics (ROC) curve were used to evaluate and validate the nomogram models. RESULTS: There were 8898 PGL patients in the SEER cohort, most of whom were married men over the age of 60, 16.1% of the primary tumors were localized in the antrum and pylori of the stomach, which was similar to the composition of 127 patients in the Chinese cohort, making both groups comparable. The Nomogram of overall survival (OS) was compiled based on eight variables, including age at diagnosis, sex, race, marital status, histology, stage, radiotherapy and chemotherapy. Cancer-specific survival (CSS) nomogram was developed with eight variables, including age at diagnosis, sex, marital status, primary tumor site, histology, stage, radiotherapy and chemotherapy. The C-index of OS prediction nomogram was 0.948 (95% CI: 0.901-0.995) in the validation cohort, the calibration plots showed an optimal match and a high area below the ROC curve (AUC) was observed in both training and validation sets. Also, we established the first web-based PGL survival rate calculator ( https://yangjinru.shinyapps.io/DynNomapp/ ). CONCLUSION: The web dynamic nomogram provided an insightful and applicable tool for evaluating PGL prognosis in OS and CSS, and can effectively guide individual treatment and monitoring.

Current status of neoadjuvant therapy for locally advanced rectal cancer in Wuhan Union Hospital Cancer Center.

BACKGROUND: To analyze and explore the evolution and short-term efficacy of neoadjuvant therapy for patients with mid and low LARC in Wuhan Union Hospital Cancer Center. METHODS: Patients diagnosed with rectal cancer from January 2015 to December 2021 were collected. The treatment patterns, short-term efficacy and treatment-related adverse events (AEs) of mid and low LARC patients who received neoadjuvant therapy were analyzed. The Chi-square test was used to compare the differences between groups. RESULTS: A total of 980 patients with mid and low LARC were enrolled, over time, the proportion of patients receiving neoadjuvant therapy gradually increased, and the treatment mode of direct surgery after diagnosis was gradually watered down. More than 80% of the patients implemented radiotherapy-based neoadjuvant therapy, and the proportion of patients receiving SCRT sequential systemic therapy gradually exceeded that of LCRT combined chemotherapy after 2020. Of all patients who completed radiotherapy and underwent surgery, 170 patients received long-course chemoradiotherapy (LCRT) combined with chemotherapy (Group C) and 98 patients received short-course radiotherapy (SCRT) combined with systemic therapy (chemotherapy with or without immunotherapy) (Group D). The pathological complete response (pCR) rate in Group D was significantly higher than that in Group C (38.8% vs. 19.4%, P = 0.001). The pCR rate in the SCRT plus immunotherapy group was better than that in the group without immunotherapy (49.2% vs. 21.6%, P = 0.007). 82.3% of the patients receiving immunotherapy were treated with SCRT sequential 2-cycle CapOX plus Camrelizumab treatment, and the pCR was as high as 52.9%. Immunotherapy did not increase the incidence of Grade 3-4 AEs. CONCLUSIONS: Neoadjuvant therapy based on radiotherapy is becoming used in patients with mid and low LARC. SCRT sequential systemic therapy is increasingly widely used in LARC patients in our center. Compared with the traditional LCRT or SCRT sequential chemotherapy, SCRT sequential chemotherapy plus immunotherapy has a remarkable pCR rate and manageable toxicity. Looking forward this new treatment mode will bring lasting survival benefits to patients.

A PD-L1 Negative Advanced Gastric Cancer Patient With a Long Response to PD-1 Blockade After Failure of Systematic Treatment: A Case Report.

Background: It was widely accepted that programmed death-ligand 1 (PD-L1) positive, tumor mutational burden-high (TMB-H) or microsatellite instability-high (MSI-H) tumor are prone to have better treatment response to immune checkpoint blockade. The value of immune checkpoint blockade in PD-L1 negative gastric cancer patients has been questioned due to lower objective response rate (ORR). Case Presentation: We report an unusual case of a PD-L1 negative, proficient mismatch repair (pMMR)/microsatellite stability (MSS), tumor mutational burden-low (TMB-L) gastric cancer patient who achieved good response to immune checkpoint blockade after failure of systematic treatment. Multiple lymph nodes and bone metastases are the main characteristics of this patient. The patient survived for more than 30 months after diagnosis. Conclusions: This case suggested that PD-L1 negative gastric cancer patient may also benefit from immune checkpoint blockade. In gastric cancer, patients with lymph node metastasis may be potential beneficiaries.

A Nasopharyngeal Carcinoma Patient With COVID-19 Infection After Immunotherapy: A Case Report and Literature Review.

BACKGROUND/AIM: Novel coronavirus infection in a cancer patient treated with immunotherapy, requires high attention. CASE REPORT: Clinical and radiological data were obtained from the electronic medical record. Pharynx swab was tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by reverse transcription-polymerase chain reaction (RT-PCR). The nasopharyngeal carcinoma patient developed fever on the third day after chemotherapy and immunotherapy. Laboratory examination showed lymphocytopenia. On the sixth day, chest computed tomography (CT) images showed bilateral scattered ground-glass opacities and reticulation. Pharynx swab was positive for SARS-CoV-2 nucleic acid and the patient was confirmed as having Coronavirus Disease 2019 (COVID-19). Unfortunately, despite aggressive treatment after the diagnosis of COVID-19, the patient died quickly. CONCLUSION: The patient with nasopharyngeal carcinoma in this case developed severe COVID-19 after receiving immunotherapy. For patients treated with immune checkpoint inhibitors (ICIs) in epidemic areas, the safety of ICIs in cancer patients infected with SARS-CoV-2 should be considered.