Intensive cycles of neoadjuvant camrelizumab combined with chemotherapy in locally advanced esophageal squamous cell carcinoma: a single-arm, phase II trial.

BACKGROUND: Two cycles of neoadjuvant PD-1 blockade plus chemotherapy induced favorable pathological response and tolerant toxicity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, approximately 25% of patients relapsed within 1 year after surgery, indicating that a short course of treatment may not be sufficient. Therefore, exploring the effects of intensive treatment is needed for optimal clinical outcomes. METHODS: Locally advanced ESCC patients were administered three cycles of camrelizumab plus nab-paclitaxel and capecitabine, followed by thoracoscopic esophagectomy. The primary endpoint was pathologic response. Secondary endpoints included safety, feasibility, radiologic response, survival outcomes, and immunologic/genomic correlates of efficacy. RESULTS: Forty-seven patients were enrolled in the study. Forty-two patients received surgery, and R0 resection was achieved in all cases. The complete and major pathological response rates were 33.3% and 64.3%, respectively, and the objective response rate was 80.0%. Three cycles of treatment significantly improved T down-staging compared to two cycles (P = 0.03). The most common treatment-related adverse events were grades 1-2, and no surgical delay was reported. With a median follow-up of 24.3 months, the 1-year disease-free survival and overall survival rates were both 97.6%, and the 2-year disease-free survival and overall survival rates were 92.3% and 97.6%, respectively. Three patients experienced disease recurrence or metastasis ranging from 12.5 to 25.8 months after surgery, and one patient died 6 months after surgery due to cardiovascular disease. Neither programmed death-ligand 1 expression nor tumor mutational burden was associated with pathological response. An increased infiltration of CD56dim natural killer cells in the pretreatment tumor was correlated with better pathological response in the primary tumor. CONCLUSIONS: It seems probable that intensive cycles of neoadjuvant camrelizumab plus nab-paclitaxel and capecitabine increased tumor regression and improved survival outcomes. Randomized controlled trials with larger sample sizes and longer follow-up periods are needed to validate these findings. Trial registration Chinese Clinical Trial Registry, ChiCTR2000029807, Registered February 14, 2020, https://www.chictr.org.cn/showproj.aspx?proj=49459 .

Neoadjuvant chemoradiotherapy for patients with unresectable radically locally advanced colon cancer: a potential improvement to overall survival and decrease to multivisceral resection.

BACKGROUND: The management of unresectable locally advanced colon cancer (LACC) remains controversial, as resection is not feasible. The goal of this study was to evaluate the treatment outcomes and toxicity of neoadjuvant chemoradiotherapy (NACRT) followed with surgery and adjuvant chemotherapy in patients with unresectable radically LACC. METHODS: We included patients who were diagnosed at our institution, 2010-2018. The neoadjuvant regimen consisted of radiotherapy and capecitabine/ 5-fluorouracil-based chemotherapy. RESULTS: One hundred patients were identified. The median follow-up time was 32 months. The R0 resection rate, adjusted nonmultivisceral resection rate and bladder preservation rate were 83.0, 43.0 and 83.3%, respectively. The pCR and clinical-downstaging rates were 18, and 81.0%%, respectively. The 3-year PFS and OS rates for all patients were 68.6 and 82.1%, respectively. Seventeen patients developed grade 3-4 myelosuppression, which was the most common adverse event observed after NACRT. Tumor perforation occurred in 3 patients during NACRT. The incidence of grade 3-4 surgery-related complications was 7.0%. Postoperative anastomotic leakage was observed in 3 patients. CONCLUSIONS: NACRT followed by surgery was feasible and safe for selected patients with LACC, and can be used as a conversion treatment to achieve satisfactory downstaging, long-term survival and quality of life, with acceptable toxicities.

Clinical presentation and CT/MRI findings of alveolar soft part sarcoma: a retrospective single-center analysis of 14 cases.

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a relatively rare malignant tumor and early diagnosis and appropriate treatment for ASPS are essential for a good prognosis. PURPOSE: To retrospectively review the clinical presentation and computed tomography (CT) and magnetic resonance imaging (MRI) findings of ASPS so as to improve the accuracy of imaging diagnosis. MATERIAL AND METHODS: Fourteen patients with pathologically proven ASPS were enrolled. Their clinical and imaging findings were retrospectively reviewed. RESULTS: The median age of the patients was 29 years (range, 13-37 years). Most tumors were located in the soft tissues of the trunk and lower limbs. The median maximal diameter of the masses was 91 mm. Thirteen masses presented with ovoid or irregular shapes. Eleven masses had less clear boundaries. Compared with the adjacent muscles, the masses were isodense or hypodense on CT, hypo-, iso-, or hyperintense on T1-weighted images, and heterogeneous hyperintense on T2-weighted images. Intense enhancement was seen after contrast agent administration, with prominent intra- or peri-tumoral feeders on CT or flow voids on MRI. By the end of the last follow-up, 13 patients had distant metastasis and three patients had local recurrence. CONCLUSION: ASPS should be included in the differential diagnosis when a bulky, heterogeneous soft tissue mass in the trunk and the lower limbs with intense enhancement after contrast administration and prominent intra- or peri-tumoral feeders on CT or flow voids on MRI is seen, particularly in young patients.

[The Identification of Lettuce Varieties by Using Unsupervised Possibilistic Fuzzy Learning Vector Quantization and Near Infrared Spectroscopy].

To solve the noisy sensitivity problem of fuzzy learning vector quantization (FLVQ), unsupervised possibilistic fuzzy learning vector quantization (UPFLVQ) was proposed based on unsupervised possibilistic fuzzy clustering (UPFC). UPFLVQ aimed to use fuzzy membership values and typicality values of UPFC to update the learning rate of learning vector quantization network and cluster centers. UPFLVQ is an unsupervised machine learning algorithm and it can be applied to classify without learning samples. UPFLVQ was used in the identification of lettuce varieties by near infrared spectroscopy (NIS). Short wave and long wave near infrared spectra of three types of lettuces were collected by FieldSpec@3 portable spectrometer in the wave-length range of 350-2 500 nm. When the near infrared spectra were compressed by principal component analysis (PCA), the first three principal components explained 97.50% of the total variance in near infrared spectra. After fuzzy c-means (FCM). clustering was performed for its cluster centers as the initial cluster centers of UPFLVQ, UPFLVQ could classify lettuce varieties with the terminal fuzzy membership values and typicality values. The experimental results showed that UPFLVQ together with NIS provided an effective method of identification of lettuce varieties with advantages such as fast testing, high accuracy rate and non-destructive characteristics. UPFLVQ is a clustering algorithm by combining UPFC and FLVQ, and it need not prepare any learning samples for the identification of lettuce varieties by NIS. UPFLVQ is suitable for linear separable data clustering and it provides a novel method for fast and nondestructive identification of lettuce varieties.

CT Characterization of Duodenal Gastrointestinal Stromal Tumors.

OBJECTIVE: Diagnosis and staging of duodenal gastrointestinal stromal tumors (GISTs) by noninvasive imaging is critical for effective treatment, but the imaging features of duodenal GISTs remain largely undefined because of their rarity. The purpose of this article was to characterize duodenal GISTs using CT. MATERIALS AND METHODS: Thirty-four patients with duodenal GISTs were analyzed by clinical symptom evaluation, pathologic examination, and CT in this retrospective study. Unenhanced and contrast-enhanced examinations were performed in all patients. Imaging characteristics, including the lesion location, size, growth pattern, ulceration, internal components, arterial blood supply, intratumoral arterioportal shunting, intratumoral vessels, rim enhancement, and enhancement patterns were reviewed. RESULTS: The duodenal GISTs were solitary masses with well-defined margins. The average diameter was 7.1 cm. The second portion was the most common site (20/34). Ulceration was a common feature (15/34). Calcification was uncommon (3/34), and mixed growth pattern was more common (26/34). Rim enhancement (24/34) and mixed enhancement pattern (15/34) were common. Arterial blood supply, intratumoral vasculature, and draining veins were all detected and were obvious on the arterial phase. The portal venous trunk and superior mesenteric vein were the main veins into which early arterioportal shunting drained. CONCLUSION: Primary duodenal GISTs are generally large, well-defined, heterogeneously enhancing, and hypervascular masses with a prominent mixed growth pattern on CT images. Our findings suggest that CT can help depict the origin of the tumoral arteries and draining veins on the arterial phase and may be a key defining diagnostic feature for duodenal GISTs.

Primary renal synovial sarcoma: computed tomography imaging findings.

BACKGROUND: A synovial sarcoma arising from the kidney is extremely rare. To date, few data are available on their radiological features. PURPOSE: To identify the computer tomography (CT) imaging findings of primary renal synovial sarcomas (PRSSs). MATERIAL AND METHODS: Five cases of PRSS confirmed by histopathological and cytogenetic studies were retrospectively analyzed. All patients had undergone unenhanced and multiphase enhanced CT examinations (one patient underwent CT twice). The CT characteristics, including shape, size, margin, attenuation, and enhancement pattern after intravenous contrast medium injection, were analyzed. RESULTS: The study involved two female and three male patients (mean age, 27.4 years; range, 15-43 years). Unenhanced CT showed completely or partly well-defined masses, with heterogeneous (n = 5) or homogeneous (n = 1) patchy low density. On multiphase contrast-enhanced CT, in five of the six CT examinations, the tumors appeared as solid-cystic masses with cyst walls or pseudo-capsules, and demonstrated moderately heterogeneous (n = 5) and/or septate enhancement (n = 2), with a "rapid wash-in and slow wash-out" pattern of enhancement in the solid component. Only one tumor showed a simple cyst appearance and developed an irregular, intratumoral, septate soft density 8 months later. A renal vein and inferior vena cava thrombus was noticed in one patient, while lymphadenopathy was not observed in any patient. CONCLUSION: PRSS should be included in the differential diagnosis when an adolescent or young adult presents with a renal neoplasm appearing as a solid-cystic mass with well-defined borders, a cystic wall or pseudo-capsule, heterogeneous or septate enhancement, a "rapid wash-in and slow wash-out" pattern of enhancement in the solid component, and no sign of lymphadenopathy.

Simple measurements on diffusion-weighted MR imaging for assessment of complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

PURPOSE: To determine diagnostic performance of simple measurements on diffusion-weighted MR imaging (DWI) for assessment of complete tumour response (CR) after neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC) by signal intensity (SI) and apparent diffusion coefficient (ADC) measurements. MATERIALS AND METHODS: Sixty-five patients with LARC who underwent neoadjuvant CRT and subsequent surgery were included. Patients underwent pre-CRT and post-CRT 3.0 T MRI. Regions of interest of the highest brightness SI were included in the tumour volume on post-CRT DWI to calculate the SIlesion, rSI, ADClesion and rADC; diagnostic performance was compared by using the receiver operating characteristic (ROC) curves. In order to validate the accuracy and reproducibility of the current strategy, the same procedure was reproduced in 80 patients with LARC at 1.5 T MRI. RESULTS: Areas under the ROC curve for identification of a CR, based on SIlesion, rSI, ADClesion, and rADC, respectively, were 0.86, 0.94, 0.66, and 0.71 at 3.0 T MRI, and 0.92, 0.91, 0.64, and 0.61 at 1.5 T MRI. CONCLUSION: Post-CRT DWI SIlesion and rSI provided high diagnostic performance in assessing CR and were significantly more accurate than ADClesion, and rADC at 3.0 T MRI and 1.5 T MRI. KEY POINTS: • Signal intensity (SI lesion ) and rSI are accurate for assessment of complete response. • rSI seems to be superior to SI lesion at 3.0 T MRI. • ADC or rADC measurements are not accurate for assessment of complete response.

Crucial computed tomography and magnetic resonance imaging findings of fallopian tubal tuberculosis for diagnosis: a retrospective study of 26 cases.

Background: Fallopian tubal tuberculosis (FTTB), which typically presents with non-specific clinical symptoms and mimics ovarian malignancies clinically and radiologically, often affects young reproductive females and can lead to infertility if not promptly managed. Early diagnosis by imaging modalities is crucial for initiating timely anti-tuberculosis (anti-TB) treatment. Currently, comprehensive radiological descriptions of this relatively rare disease are limited. We aimed to comprehensively investigate the computed tomography (CT) and magnetic resonance imaging (MRI) characteristics of FTTB in patients from the Kashi area, which has the highest incidence of TB in China, to extend radiologists' understanding of this disease. Methods: We conducted a retrospective cross-sectional study of 26 patients diagnosed with FTTB at the First People's Hospital of Kashi Area. All the patients underwent abdominal and pelvic contrast-enhanced CT examinations and/or pelvic contrast-enhanced MRI from January 2017 to June 2022. The imaging findings were evaluated in consensus by two experienced radiologists specialized in abdominal and pelvic imaging. The evaluated sites included the fallopian tubes, ovaries, peritoneum, mesentery, retroperitoneal nodes, and parailiac nodes. The patient characteristics are reported using descriptive statistics. The patient imaging results are presented as percentages. The normally distributed continuous variables are reported as the mean ± standard deviation (SD), and otherwise as the median with the interquartile range (IQR). Results: The median age of the patients was 27 years (IQR: 25-34 years). Bilateral involvement of the fallopian tubes was observed in all patients. The tubal wall appeared coarse with tiny intraductal nodules in 96% (25 of 26) of the patients. The mean CT value of the tubal contents was 34 Hounsfield units (HUs; SD: 3.3 HUs). Ascites was present in 92% (24 of 26) of the patients, with 20 patients showing encapsulated effusion. Among these patients, 20 exhibited the highest CT values of ascites (>20 HUs). Linear enhancement of the parietal peritoneum was observed in 88% (23 of 26) of the patients, of whom 22 had peritoneal nodules measuring a median diameter of 0.4 cm (IQR: 0.3-0.6 cm). Eight patients had retroperitoneal and parailiac nodal enlargement, of whom two showed nodal necrosis, and none displayed nodal calcification. Conclusions: FTTB is consistently accompanied by tuberculous peritonitis. FTTB typically presents with tubal dilation, and coarseness and nodules in the lumen, as well as intraductal caseous material and calcification. Tuberculous peritonitis exhibits high-density ascites, peritoneal adhesion, linear enhancement of the parietal peritoneum, and tiny peritoneal nodules. The co-occurrence of these features strongly suggests a diagnosis of FTTB.

Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial.

Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total complete response (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%-37.8%) and 44.8% (30/67, 95% CI 32.6%-57.0%) in the control and experimental arm, respectively, with significant difference (p = 0.031 for chi-squared test). Response ratio is 1.667 (95% CI 1.035-2.683). Immunohistochemistry shows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergistic effect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimab to NACRT significantly increases the CR rate in pMMR LARC, with a manageable safety profile. PD-L1 positivity may help identify patients who might benefit most from the combination therapy.

Artificial intelligence for diagnosis and prognosis prediction of natural killer/T cell lymphoma using magnetic resonance imaging.

Accurate diagnosis and prognosis prediction are conducive to early intervention and improvement of medical care for natural killer/T cell lymphoma (NKTCL). Artificial intelligence (AI)-based systems are developed based on nasopharynx magnetic resonance imaging. The diagnostic systems achieve areas under the curve of 0.905-0.960 in detecting malignant nasopharyngeal lesions and distinguishing NKTCL from nasopharyngeal carcinoma in independent validation datasets. In comparison to human radiologists, the diagnostic systems show higher accuracies than resident radiologists and comparable ones to senior radiologists. The prognostic system shows promising performance in predicting survival outcomes of NKTCL and outperforms several clinical models. For patients with early-stage NKTCL, only the high-risk group benefits from early radiotherapy (hazard ratio = 0.414 vs. late radiotherapy; 95% confidence interval, 0.190-0.900, p = 0.022), while progression-free survival does not differ in the low-risk group. In conclusion, AI-based systems show potential in assisting accurate diagnosis and prognosis prediction and may contribute to therapeutic optimization for NKTCL.

Is early surveillance with CT scan necessary in patients with stage II/III colorectal cancer: a retrospective study.

BACKGROUND AND OBJECTIVES: This analysis aims to evaluate the value of early surveillance within 6 months after resection for stage II/III colorectal cancer (CRC). METHODS: Patients with stage II/III CRC who received surgery with curative intent for CRC were included. CT scans of the chest, abdomen, and pelvis performed within 6 months after surgery were evaluated. RESULTS: Among 150 patients included in the study, 10 patients (1 occurred in stage II disease and 9 occurred in stage III) were diagnosed as recurrence within 6 months after surgery. The proportion of patients diagnosed as recurrence was significantly higher in stage III disease than in stage II disease (P = 0.01). The likelihood of recurrence within 6 months was associated with the extent of lymph node metastases (r = 0.205, P = 0.012). Three patients with recurrent disease underwent salvage resection with curative intent. CONCLUSIONS: Early surveillance with CT scan within 6 months after curative resection may not be necessary for stage II disease. Although, the strategy may be helpful for stage III disease considering the high incidence of salvage surgery for recurrence disease, the early detection of recurrence could not be translated into survival benefit.

CT and MRI of radiation-induced sarcomas of the head and neck following radiotherapy for nasopharyngeal carcinoma.

AIM: To investigate the radiological findings of head and neck radiation-induced sarcomas (RISs) following radiotherapy for nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Fifty-nine patients with RISs were identified. Imaging characteristics on computed tomography (CT) and magnetic resonance imaging (MRI), including lesion location, extent, size, margin, internal architecture, pattern, and degree of enhancement, together with patient characteristics at NPC diagnosis and latency periods, were reviewed. RESULTS: The study included 20 women and 39 men, with a median age of 49 years (range 30-71 years). The median latency was 9 years (range 3-37 years). The median radiation dose at the site of RIS was 66 Gy (range 44-78 Gy). The most common histological RIS types were fibrosarcoma (44.1%) and osteosarcoma (30.5%). The most common RIS sites were the paranasal sinuses and the nasal cavity (39%), the neck (16.9%), and the mandible (15.3%). The mean size was 5.1 cm (range 1.2-8.6 cm). Overall, 78% of lesions extended to adjacent spaces and 66.1% were accompanied by bone destruction. Heterogeneous density/signal intensity before and after enhancement was seen in all lesions on imaging. Marked lesion enhancement was noted in 49 cases (76.3%). CONCLUSIONS: The radiologist should be aware of the different sites at which RISs occur and the radiological appearance of the wide variety of RIS subtypes. Careful imaging follow-up is necessary for early detection of RISs in patients with NPC after radiotherapy.

Hepatic angiomyolipoma: CT and MR imaging findings with clinical-pathologic comparison.

OBJECTIVE: The objective of this study is to evaluate the clinical, pathologic, and computed tomography (CT) and/or magnetic resonance imaging (MRI) findings of hepatic angiomyolipoma (HAML) and to improve the diagnostic efficacy of the tumor. MATERIALS AND METHODS: Clinical, pathologic, and imaging findings were retrospectively evaluated in 18 patients with HAML. Two patients underwent both CT and MRI, ten underwent CT alone, and six underwent MRI alone. Unenhanced and contrast-enhanced examinations were performed in all patients. Imaging characteristics, such as the lesion location, lesion diameter, presence of early draining veins, attenuation/signal intensity of the lesions on imaging, and enhancement pattern were reviewed. RESULTS: There were 3 male and 15 female patients. HAML was seen as a well-defined, solitary mass on imaging with medium size (mean diameter, 5.9 cm). Fat was detected in ten patients. Calcification was noted in two patients and cystic degeneration was seen in one patient. Hepatic cirrhosis and capsule were not detected in all patients. The mean attenuation values exceeded 120 hounsfield units (HU) in 11 patients (91.7%). Peripherally decreasing enhancement rim as well as early draining vein was seen in 15 patients (83.3%). The early draining veins were all hepatic veins. Tumor vessels were noted in all patients. CONCLUSION: The presence of early draining vein, peripheral decreasing enhancement rim, and the absence of tumor capsule in the hypervascular hepatic tumor on CT and/or MRI together with normal alpha fetal protein may be helpful for the diagnosis of HAML in non-cirrhotic liver.

Abnormal baseline brain activity in patients with HBV-related cirrhosis without overt hepatic encephalopathy revealed by resting-state functional MRI.

Neurocognitive dysfunction of varying degrees is common in patients with hepatitis B virus-related cirrhosis (HBV-RC) without overt hepatic encephalopathy (OHE). However, the neurobiological mechanisms underlying these dysfunctions are not well understood. We sought to identify changes in the neural activity of patients with HBV-RC without OHE in the resting state by using the amplitude of low-frequency fluctuation (ALFF) method and to determine whether these changes were related to impaired cognition. Resting-state functional MRI data from 30 patients with HBV-RC and 30 healthy controls matched for age, sex, and years of education were compared to determine any differences in the ALFF between the two groups. Cognition was measured with the psychometric hepatic encephalopathy score (PHES), and the relationship between these scores and ALFF variation was assessed. Compared with controls, patients showed widespread lower standardized ALFF (mALFF) values in visual association areas (bilateral lingual gyrus, middle occipital gyrus, and left inferior temporal gyrus), motor-related areas (bilateral precentral gyrus, paracentral lobule, and right postcentral gyrus), and the default mode network (bilateral cuneus/precuneus and inferior parietal lobule). Higher mALFF values were found in the bilateral orbital gyrus/rectal gyrus. In patients, mALFF values were significantly positive correlated with the PHES in the right middle occipital gyrus and bilateral precentral gyrus. Our findings of resting-state abnormalities in patients with HBV-RC without OHE suggest that neurocognitive dysfunction in patients with HBV-RC without OHE may be caused by abnormal neural activity in multiple brain regions.

Prognostic value of MR-detected mandibular nerve involvement: potential indication for future individual induction chemotherapy in T4 nasopharyngeal carcinoma.

PURPOSE: To investigate the prognostic significance of MR-detected mandibular nerve involvement (MNI) and its value for induction chemotherapy (IC) administration in patients with nasopharyngeal carcinoma (NPC) and T4 disease. METHODS: This retrospective study enrolled 792 non-metastatic, biopsy-proven NPC patients. Univariate and multivariate analysis were used to evaluate potential prognosticators. The inter-observer agreement was assessed by the kappa values. RESULTS: MR-detected MNI was observed in 141 (72.3%) patients among 195 patients with T4 disease, with excellent agreement between the readers (kappa = 0.926). Patients with MR-detected MNI presented better 5-year overall survival (OS) (hazard ratio [HR], 0.40; P = 0.006) than those with MR-negative MNI. Of these patients, IC treatment was verified as an independent factor (HR: 0.35; P = 0.014) with preferable effect on OS. CONCLUSION: MR-detected MNI could serve as an independent favorable prognostic predictor for OS in NPC patients with stage T4, which should be considered for stratifying these patients for IC administration.

Are more courses of immunochemotherapy beneficial for the short-term outcome of locally advanced esophageal squamous cell carcinoma?

BACKGROUND: Immune checkpoint inhibitor (ICI) monotherapy and neoadjuvant immunochemotherapy have shown promising results in esophageal carcinoma. However, it is still unclear whether more courses of immunochemotherapy are therapeutically better. We aimed to investigate the safety and efficacy of three courses of neoadjuvant treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients with locally advanced ESCC received three courses of camrelizumab plus nab-paclitaxel and capecitabine before undergoing surgery. Additionally, patients received safety, computed tomography (CT), and endoscopy (with endoscopic ultrasonography and mucosal biopsy) assessments before and in the second and third courses of treatment. We used the CT and endoscopic assessment results from the second and third courses for comparison. RESULTS: From May 2020 to December 2021, 47 patients were enrolled at Sun Yat-sen University Cancer Center. In our study, 43 patients completed three courses of preoperative chemotherapy combined with anti-Programmed cell death-1 (PD-1) therapy and radical surgical resection. The toxicity of the third course of immunochemotherapy was mild and well tolerated without increased treatment-related adverse events (TRAEs) and mortality compared with that of the second course of treatment. In terms of efficacy, an additional course of treatment after the second course of treatment was effective, with increased CT and endoscopy T (clinical T stage) downstaging rates by 16.3% and 25.9%, N (clincial N stage) downstaging rates by 7.0% and 11.1%, and objective response rates (ORRs) by 13.6% and 22.0%, respectively. CONCLUSIONS: Regardless of downstaging or ORR, three courses of immunochemotherapy appear to be superior to two courses of treatment without increasing TRAEs.

Total neoadjuvant treatment to increase the clinical complete response rate for distal locally advanced rectal cancer (TESS): A study protocol of a prospective, open-label, multicenter, single-arm, phase 2 trial.

BACKGROUND: Standard treatment of locally advanced rectal cancer (LARC) was neoadjuvant chemoradiotherapy (CRT), followed by total mesorectal excision (TME). Total neoadjuvant treatment (TNT), a new concept, attempts to deliver both systemic chemotherapy and neoadjuvant CRT prior to surgery. Patients treated with neoadjuvant chemotherapy were more likely to show higher tumor regression. The objective of this trial was to increase complete clinical rate (cCR) for LARC patients by optimizing tumor response, using TNT regimen as compared to conventional chemoradiotherapy. TESS, a prospective, open-label, multicenter, single-arm, phase 2 study, is underway. METHODS: Main inclusion criteria include cT3-4aNany or cT1-4aN+ rectal adenocarcinoma aged 18-70y; Eastern Cooperative Oncology Group (ECOG) performance 0-1; location ≤5 cm from anal verge. Ninety-eight patients will receive 2 cycles of neoadjuvant chemotherapy Capeox (capecitabine + oxaliplatin) before, during, and after radiotherapy 50Gy/25 fractions, before TME (or other treatment decisions, such as Watch and Wait strategy) and adjuvant chemotherapy capecitabine 2 cycles. Primary endpoint is the cCR rate. Secondary endpoints include ratio of sphincter preservation strategy; pathological complete response rate and tumor regression grade distribution; local recurrence or metastasis; disease-free survival; locoregional recurrence-free survival; acute toxicity; surgical complications; long-term anal function; late toxicity; adverse effect, ECOG standard score, and quality of life. Adverse events are graded per Common Terminology Criteria for Adverse Events V5.0. Acute toxicity will be monitored during antitumor treatment, and late toxicity will be monitored for 3 years from the end of the first course of antitumor treatment. DISCUSSION: The TESS trial aims to explore a new TNT strategy, which is expected to increase the rate of cCR and sphincter preservation rate. This study will provide new options and evidence for a new sandwich TNT strategy in patients with distal LARC.

Neoadjuvant PD-1 blockade with sintilimab in mismatch-repair deficient, locally advanced rectal cancer: an open-label, single-centre phase 2 study.

BACKGROUND: The current standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiotherapy followed by radical surgery, but this approach can lead to multiple complications. We aimed to investigate the clinical activity and safety of neoadjuvant therapy with sintilimab, a single-agent PD-1 antibody, in patients with mismatch-repair deficient locally advanced rectal cancer. METHODS: This open-label, single-arm, phase 2 study was done at the Sun Yat-sen University Cancer Center, Guangzhou, China. Patients aged 18-75 years with mismatch-repair deficient or microsatellite instability-high locally advanced rectal cancer were enrolled and received neoadjuvant sintilimab monotherapy (200 mg by intravenous infusion) every 21 days. After an initial four cycles of treatment, patients and clinicians could choose one of the following options: total mesorectal excision surgery, followed by four cycles of adjuvant sintilimab with or without CapeOX chemotherapy (capecitabine 1000 mg/m2, orally administered twice daily on days 1-14; oxaliplatin 130 mg/m2, intravenously administered on day 1 every 3 weeks), determined by clinicians; or another four cycles of sintilimab followed by radical surgery or observation (only for patients with a clinical complete response; also known as the watch and wait strategy). The primary endpoint was the complete response rate, which included both a pathological complete response after surgery and a clinical complete response after completion of sintilimab treatment. Clinical response was evaluated by digital rectal examination, MRI, and endoscopy. Response was assessed in all patients who received treatment at least until the first tumour response assessment, after the first two cycles of sintilimab. Safety was analysed in all patients who received at least one dose of treatment. This trial is closed to enrolment and is registered with ClinicalTrials.gov (NCT04304209). FINDINGS: Between Oct 19, 2019, and June 18, 2022, 17 patients were enrolled and received at least one dose of sintilimab. The median age was 50 years (IQR 35-59) and 11 (65%) of 17 patients were male. One patient was excluded from efficacy analyses because they were lost to follow-up after the first sintilimab cycle. Of the remaining 16 patients, six underwent surgery, of whom three had a pathological complete response. Nine other patients had a clinical complete response and chose the watch and wait strategy. One patient had a serious adverse event and discontinued treatment; this patient did not have a complete clinical response and refused to undergo surgery. A complete response was thus noted for 12 (75%; 95% CI 47-92) of 16 patients. One of the three patients who underwent surgery but did not have a pathological complete response showed an increase in tumour volume after the initial four cycles of sintilimab (at which point they underwent surgery); this patient was deemed to have primary resistance to immune checkpoint inhibitors. After a median follow-up of 17·2 (IQR 8·2-28·5) months, all patients were alive and none had disease recurrence. Only one (6%) patient had a grade 3-4 adverse event, which was deemed a serious adverse event (grade 3 encephalitis). INTERPRETATION: The preliminary results of this study suggest that anti-PD-1 monotherapy is effective and tolerable for patients with mismatch-repair deficient locally advanced rectal cancer and could potentially spare some patients from radical surgery. Longer treatment courses might be needed to achieve maximum effects in some patients. Longer follow-up is also needed to observe the duration of response. FUNDING: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, Science and Technology Program of Guangzhou, and Innovent Biologics.

Assessment of Cone-Beam Breast Computed Tomography for Predicting Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer: A Prospective Study.

Background: Response surveillance of neoadjuvant chemotherapy is needed to facilitate treatment decisions. We aimed to assess the imaging features of cone-beam breast computed tomography (CBBCT) for predicting the pathologic response of breast cancer after neoadjuvant chemotherapy. Methods: This prospective study included 81 women with locally advanced breast cancer who underwent neoadjuvant chemotherapy from August 2017 to January 2021. All patients underwent CBBCT before treatment, and 55 and 65 patients underwent CT examinations during the midtreatment (3 cycles) and late-treatment phases (7 cycles), respectively. Clinical information and quantitative parameters such as the diameter, volume, surface area, and CT density were compared between pathologic responders and nonresponders using the T-test and the Mann-Whitney U test. The performance of meaningful parameters was evaluated with the receiver operating characteristic curve, sensitivity, and specificity. Results: The quantitative results for the segmented volume, segmented surface area, segmented volume reduction, maximum enhancement ratio, wash-in rate and two-minute enhancement value in the mid- and late-treatment periods had predictive value for pathologic complete response. The area under the curve for the prediction model after multivariate regression analysis was 0.874. Conclusion: After comparing the outcomes of each timepoint, mid- and late-treatment parameters can be used to predict pathologic outcome. The late-treatment parameters showed significant value with a predictive model.