Assessment Of Tumor Response Research Articles

The dual-crosslinked prospective values of RAI14 for the diagnosis and chemosurveillance in triple negative breast cancer

Objective The exploration of non-invasive biomarkers for assessing tumor response is critical to optimize treatment decisions. In this study, we aimed at determining the potential role of RAI14 in the early diagnosis and evaluation of chemotherapy efficacy in triple-negative breast cancer (TNBC). Methods We recruited 116 patients newly diagnosed with breast cancer, 30 patients with benign breast disease and 30 healthy controls. In addition, 57 TNBC patients were collected in serum at different time points (C0, C2 and C4) for chemotherapy monitoring. The expression of serum RAI14 and CA15-3 were quantified by Elisa and electrochemiluminescence assay, respectively. Then we compared the performances of markers with the chemotherapy efficacy assessed by imaging. Results RAI14 is significantly overexpressed in TNBC and is linked to adverse clinicopathological features such as tumor burden, CA15-3 levels and the ER, PR, and HER2 status of the patients. ROC curve analysis showed that RAI14 improves the diagnostic performance for CA15-3(AUCRAI14 = 0.934 vs. AUCCA15-3 = 0.836), especially embodied in early-stage breast cancer diagnosis and patients with CA15-3 negativity. Furthermore, RAI14 behaves well in reproducing treatment response which was consistent with clinical Imaging assessment. Conclusions Recent studies showed that RAI14 has a complementary effect to CA15-3 and a test combining the two parameters can improve the detection rate of early triple-negative breast cancer. At the same time, RAI14 plays a more important role in chemotherapy monitoring than CA15-3 as the change in its concentration is in line with the tumor volume variation. Taken together, RAI14 is a reliable novel marker in the early diagnosis and chemotherapy monitoring of triple-negative breast cancer.

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

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. 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). 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). 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. The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, Science and Technology Program of Guangzhou, and Innovent Biologics.

Abstract P3-04-04: Correlation of Mammographic Microcalcifications with Final Surgical Pathology after Neoadjuvant Chemotherapy for Breast Cancer

Abstract Introduction: Benefits of neoadjuvant chemotherapy (NAC) in breast cancer include de-escalating surgical management, treating occult systemic metastases and the assessment of in-vivo tumor response. Guidelines for post-NAC imaging to assess response lack specificity on appropriateness and utility of individual imaging modalities for surgical planning. Mammographic microcalcifications are a confounder that are not well studied. We examined the correlation between the mammographic extent of microcalcifications present post-NAC, corresponding MRI lesions, and definitive surgical pathology. Methods: In this retrospective cohort study, patients with calcifications on pre-NAC mammograms were collected from a database of consecutive breast cancer patients receiving NAC at an academic center between January 1st 2014 – December 31st 2019. The primary objective was to determine how the maximum diameter of post-NAC calcifications correlates with final surgical pathology, stratified by tumor receptor subtype. The secondary objectives were to assess correlation of the maximum diameter on final pathology with the maximum diameter of (1) post-NAC mammographic mass (if present) and (2) post-NAC MRI, mass (ME) and non-mass enhancement (NME). Parameters on final surgical pathology included the diameters of invasive disease, ductal carcinoma in-situ (DCIS) and the tumor bed (TB). Pearson’s correlation coefficient was used to evaluate statistical significance and considered strong if R2 ≥70%, moderate if R2 = 25-70% and weak if R2 ≤25%. Results: 343 patients received NAC, of which 157 were excluded for lack of calcifications (n=147), lack of imaging reports (n=8) or inflammatory breast cancer (n=2). 186 patients met the inclusion criteria with a mean age of 49.9 years. 34 (18.3%) patients had triple negative breast cancers (TNBCs). Mammographic calcifications correlated poorly with residual invasive disease (R2= 10.8%), overestimating by 57%. TNBCs demonstrated the strongest correlation between microcalcifications and invasive disease (R2=83%), but calcifications overestimated pathology by 41%. Mammographic calcifications correlated moderately with the TB (R2= 50.3%) and poorly with DCIS (R2 = 3.4%). By subtype, both correlations were strong in TNBCs (R2 = 76.3% and 77.9% respectively). Similarly, focal mass on mammography correlated poorly with pathology except in TNBCs, which correlated moderately with all three pathology parameters (Table 1). In patients with calcifications on mammography, MRI ME and NME correlated weakly with invasive disease, except in TNBCs, where correlation was moderate in ME (R2 = 37.7%) and NME (R2 = 28.4%). Conclusion: In breast cancer patients with microcalcifications, current post-NAC imaging modalities appear to overestimate the extent of residual disease. Surgical excision of all residual microcalcifications may maximize oncologic safety but may also represent over-treatment. Ongoing feasibility trials on surgical omission rely on post-NAC imaging to determine trial candidacy. Our data suggests that potentially eligible patients are excluded on the basis of post-NAC imaging overestimating the extent of residual disease. Further studies are needed to determine the most accurate imaging correlate of residual disease after NAC to plan better surgeries, identify candidates for surgical omission and establish optimal post-NAC imaging guidelines. Current imaging modalities appear most accurate for TNBCs and may be more reliable at identifying exceptional responders for surgical omission in this subtype. Table 1. Summary of Correlation Analyses in Overall and Triple Negative Breast Cancer (TNBC) cohorts. * Average % difference in maximal diameter calculated as (pathology – radiology)/radiology Citation Format: Riordan M. Azam, Nicole Look Hong, David Lim. Correlation of Mammographic Microcalcifications with Final Surgical Pathology after Neoadjuvant Chemotherapy for Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-04-04.

Abstract PD16-04: To monitor or not to monitor? MRI monitoring of neoadjuvant chemotherapy effect and its benefit on breast cancer patients’ pathological complete response rate

Abstract Introduction: Neoadjuvant chemotherapy (NACT) represents an essential tool for the treatment of selected breast cancer patients aimed to reduce the tumor size for a more conservative resection and to gain early information about the sensitivity to applied treatment. An effective early response assessment helps both to change the therapeutic strategy for patients nonresponding to the treatment used and to avoid the toxicity related to ineffective treatment. We assumed that changing the chemotherapy regimen might avoid the residual cancer burden (RCB) III outcome and lead to the highest possible rate of pathological complete response (pCR) achieved. We examined the benefit of MRI as a preferred method for interim response assessment to NACT with a primary focus on the relation between the pattern of responses to NACT within the MRI- monitored and non-monitored patients and the pattern of final outcomes on the RCB scale. Methods We present a real-life data-based retrospective analysis of 124 female patients with locally advanced breast carcinoma. All patients received NACT (anthracycline-based regimen followed by taxane-based regimen/early switch to taxanes after the 2nd cycle in nonresponders, and antiHER2 therapy if indicated) prior to surgery (mastectomy/breast-conserving surgery, sentinel lymph node biopsy/axillary dissection). Postoperative histopathological analysis of tumor specimens categorised 120 patients according to the RCB scale 0 – III. Four patients had surgery ex muros and were lost to follow-up. Patients were divided into two cohorts. Group A covered monitored patients with pre-treatment MRI and follow-up MRI after the 2nd cycle of NACT. If no response was detected, another follow-up MRI was indicated after the 2nd cycle of a new treatment. Group B comprised patients with no/incomplete MRI monitoring and patients without the change of therapy even though no response was detected by MRI after the 2nd cycle of NACT. Association between categorical variables was tested using chi-square tests. Statistical analysis was performed using StatsDirect® 3.3.5 (StatsDirect Ltd., Cheshire, UK). The data analysis was supported by a grant from the Cultural and Educational Grant Agency of the Ministry of Education, Science, Research, and Sport of the Slovak Republic (KEGA 041UK-4/2020). Results MRI-monitored patients had two times the odds of being RBC 0 (OR = 2.02, P = 0.122) and almost three times the odds of being RCB 0 or RCB I (OR = 2.83, P = 0.0206) than patients with no monitoring. Changing the NACT after the 2nd cycle in the cohort of monitored patients with no response to initial therapy was significantly associated with better outcomes on the RCB scale (P = 0.0042). This result was confirmed by comparing the pattern of results in patients with no response within the group of incompletely monitored patients with known MRI results after the 2nd cycle (P = 0.0257). Changing the ineffective NACT after the 2nd cycle significantly increased the proportion of RCB 0-I by 23.4%, confirming the benefit of response monitoring by MRI. Conclusion Breast cancer constitutes a heterogeneity of tumor subtypes and it is acknowledged that their behaviour during NACT is highly variable and often unpredictable. MRI represents an effective tool for the assessment of tumor response to applied NACT. To achieve the most clinically meaningful impact of the selected treatment it is critical to monitor the tumor response within the first 3 cycles. Our data clearly confirmed that clinical decisions related to the detection of early response or no response (resulting in the change of NACT) lead to better treatment outcomes and less toxicity. The rate of pCR defines the applied treatment efficacy. Every single patient with results different from RCB III has a better prognosis, reduced need for further expensive treatment and also a more favourable quality of life. These key facts need to be carefully considered when discussing the cost and benefits of MRI monitoring. Citation Format: Lucia Vanovcanova, Iveta Waszulikova, Bibiana Vertakova Krakovska. To monitor or not to monitor? MRI monitoring of neoadjuvant chemotherapy effect and its benefit on breast cancer patients’ pathological complete response rate [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD16-04.

Mesotheliomas and Benign Mesothelial Tumors: Update on Pathologic and Imaging Findings

A diverse spectrum of benign entities and malignant neoplasms originate from the monotonous mesothelium that lines the serosal membranes of the pleural, pericardial, and peritoneal cavities. The mesothelium of myriad sites shows a common origin from the lateral plate mesoderm; primary mesothelial tumors thus demonstrate similar pathogenesis, imaging findings, and treatment options. Significant changes have been made in the 2021 World Health Organization (WHO) classification schemata of the pleural and pericardial tumors on the basis of recent advances in pathology and genetics. While malignant mesotheliomas are biologically aggressive malignancies that occur primarily in patients exposed to asbestos with attendant poor survival rates, well-differentiated papillary mesothelial tumors and adenomatoid tumors charter a benign clinical course with an excellent prognosis. Mesothelioma in situ is a newly characterized entity represented by recurrent unexplained pleural effusions without any identifiable mass at imaging or thoracoscopy. Immunohistochemical markers based on BAP1, MTAP, CDKN2A, and TRAF7 gene mutations help differentiate diffuse mesotheliomas from benign mesothelial proliferations and localized mesotheliomas. Cross-sectional imaging modalities, including US, CT, MRI, and fluorine 18-fluorodeoxyglucose (FDG) PET/CT, permit diagnosis and play a major role in staging and assessing surgical resectability. Imaging studies are invaluable in providing noninvasive and quantitative assessment of tumor response in patients with unresectable disease. Owing to significant overlap in patient characteristics and pathomorphology, accurate diagnosis based on advanced histopathology techniques and genetic abnormalities is imperative for optimal management and prognostication. While patients with nonepithelioid pleural mesotheliomas benefit from immunotherapy, novel targeted therapies for CDKN2A-, NF2-, and BAP1-altered mesotheliomas are under consideration. © RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.

Abstract P4-07-40: Magnetic resonance imaging (MRI) and clinicopathological analysis of triple-negative breast cancer (TNBC) patients (pts) treated with primary anthracyclines(A)/taxanes(TX)-based chemotherapy

Abstract Background Radiological complete response (CR-MRI) to neoadjuvant chemotherapy (NAC) by MRI predicts pathologic complete response (pCR) rates in pts with TNBC treated preoperatively with A/TX-based regimens and in some studies, it correlates with disease-free survival (DFS). The main aim of this study was to assess the relevance of the MRI response to primary chemotherapy associated with clinical stage and HER2 expression (Zero vs Low), in a cohort of 143 TNBC pts treated with A and TX +/- carboplatin (CP) in the NAC setting. Methods Retrospective study of pts treated with NAC for TNBC between January 2002 and June 2021, who underwent MRI to assess tumour response before NAC, after 4 cycles of anthracycline and cyclophosphamide (AC) and after TX. Survival analysis was based on the Kaplan-Meier and survival curves were compared using the log-rank test. A p value of less than 0.05 was considered as statistically significant. Results A total of 143 TNBC pts with a median age of 52 years; 7, 63 and 73 pts had stage I, II and III disease, respectively. The NAC regimen consisted in 117 pts 4 cycles of AC followed by TX and in 24 pts the same adding CP (in 21 pts with non-CR-MRI, 2 with CR-MRI and 1 without MRI after AC). PCR was observed in 41%. Of 30 pts with CR-MRI after AC, 83% obtain a pCR (p< 0.001), and of 52 pts with CR-MRI at the end of NAC, 70.7% obtain a pCR (p< 0,001) of which 90% had a CR-MRI after AC. Adding CP increased pCR by 6% (p=0.564). According HER2-zero vs low expression, the pCR was 38% and 47% respectively, with no significant differences. With a median follow-up of 60 months, 34% recurred and 16% died of TNBC. In pts with pCR, the DFS at 5 years (y) was 96% and 47% for pts without pCR (p< 0.001), with a DFS of 91% if CR-MRI at the end of NAC and 48% if non-CR-MRI (p< 0.001). In HER2-Zero tumours the DFS at 5 y was 64% vs 66% in HER-2 low. Interestingly, overall survival (OS) at 5 y was 72% in HER2-Zero and 84% in HER2-low (p=0.080). Conclusions Performing serial MRI in the course of NAC in TNBC may be a reliable indicator of pCR, adding platinum to TX in pts with CR-MRI may increase pCR rate. HER2-Zero expression in TNBC, seems to confer worse OS rates. Citation Format: Marina Sierra Boada, Luis Antonio Fernandez, Elsa Dalmau, Gemma Llort, Maria Marin, Pablo Andreu, Natalia Lopez, Carla Climent, Marta Rodriguez, Sandra Soriano, Miquel Angel Segui. Magnetic resonance imaging (MRI) and clinicopathological analysis of triple-negative breast cancer (TNBC) patients (pts) treated with primary anthracyclines(A)/taxanes(TX)-based chemotherapy. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-40.

Abstract PD16-07: Association of MRI morphologic phenotype from unsupervised learning with breast cancer subtypes and treatment response

Abstract Background Breast cancer is a heterogeneous disease and can be categorized into clinically or biologically meaningful subtypes. Predictive models built by MRI biomarkers performed better when they are optimized by breast cancer subtype than models optimized in the full cohort [1]. Functional tumor volume (FTV) measured from breast MRI has been used to assess tumor response to neoadjuvant therapy longitudinally in the I-SPY 2 TRIAL. Tumors show distinct morphological patterns, or phenotypes, on MRI. Previous studies demonstrated that either qualitative or quantitative measurements characterizing these phenotypes may provide additional information about treatment response [2,3]. In this study, we investigated if MRI morphologic phenotypes defined by unsupervised clustering is associated with breast cancer subtype and pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). Methods A cohort of 990 patients enrolled in the I-SPY 2 TRIAL were included in this retrospective analysis. Patients were randomized to one of nine experimental drug arms or standard NAC, and pCR was assessed at surgery. DCE-MRI data acquired at pretreatment (T0) and early treatment (T1) were analyzed. Four subtypes of breast cancer were defined by immunohistochemistry (IHC) based on hormone receptor (HR) and HER2 status. Radiomic features were extracted by PyRadiomics [4] using FTV masks from DCE-MRI. MRI morphologic phenotypes were determined based on unsupervised hierarchical clustering approach on extracted radiomic shape features plus FTV using Pearson correlation with agglomerative ward linkage. The associations between the unsupervised clusters of radiomic features and FTV with four IHC subtypes and pCR were evaluated using χ2 test of independence. Cramer’s V [5] were computed to measure the strength of association (higher Cramer’s V means stronger association). P-value < 0.05 was considered statistically significant. Results Three clusters were generated by unsupervised hierarchical clustering in a population of 910 patients included in our analysis (80 patients excluded due to missing pCR or DCE-MRIs). At T0, the unsupervised clusters showed statistically significant but weak association with pCR (Cramer’s V = 0.088, p = 0.029), but the association between the clusters and HR/HER2 subtypes did not reach significance (Cramer’s V = 0.055, p = 0.48). The unsupervised clusters based on T1 shape radiomic features showed statistically significant association with both pCR and HR/HER2 subtypes (p < 0.001 for both) with Cramer’s V of 0.231 and 0.154, respectively. Our results showed stronger association between pCR and cancer subtypes with MRI shape radiomic features at T1 than at T0. Various pCR rates were observed in MRI clusters at T1. They were 56%, 36%, and 23% in Cluster 1, 2, 3, respectively. Table 1 shows pCR rates by HR/HER2 subtype in each cluster. In all sub-cohorts, pCR rate was highest in Cluster 1 and lowest in Cluster 3. In HR+/HER2-, the pCR rate in Cluster 1 was 2-fold of the pCR rates in Clusters 2 and 3-fold of Cluster 3. pCR rate was statistically significantly different depending on the MRI clusters in the sub-cohorts except for the HR/HER2+ sub-cohort: HR+/HER2-, p< 0.001; HR+/HER2+, p=0.021; HR-/HER2+, p=0.083; HR-/HER2-, p< 0.001. Conclusion MRI phenotype generated by unsupervised clustering using radiomic shape features at both pretreatment and early-treatment time points was associated with pCR outcome. Stronger association was observed at early-treatment time point. The association differed by subtype, with the strongest observed in HR+/HER2- and triple negative subtypes. Our results suggest that radiomic shape features derived from DCE-MRI may be helpful for early prediction of tumor response to NAC. Citations 1. npj Breast Cancer 6, (2020). 2. Tomography 6, (2020). 3. Annals of Surgical Oncology 20, 3823–3830 (2013). 4. Cancer Research 77, e104–e107 (2017). 5. Korean Stat Soc 42, 323–328 (2013). Table 1. pCR rate by HR/HER2 subtype in each MRI cluster at T1 Citation Format: Nu N. Le, Natsuko Onishi, David C. Newitt, Jessica E. Gibbs, Lisa J. Wilmes, Efstathios Gennatas, Barbara LeStage, Laura J. Esserman, Nola M. Hylton, Wen Li. Association of MRI morphologic phenotype from unsupervised learning with breast cancer subtypes and treatment response [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD16-07.

Efficacy and safety of neoadjuvant chemotherapy combined with PD-1 antibody for esophageal squamous cell carcinoma in the real world

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with programmed death-1 (PD-1) antibody in operable, borderline or potentially resectable locally advanced esophageal squamous cell carcinoma(ESCC) in the real world. Methods: The study retrospectively analyzed 28 patients with operable or potentially resectable locally advanced ESCC patients treated with preoperative chemotherapy combined with PD-1 inhibitor in Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 2020 to March 2021. According to the clinical TNM staging system of the 8th edition of the American Joint Committee on Cancer, there were 1, 15, 10, 1 and 1 case of stage Ⅱ, Ⅲ, ⅣA, ⅣB and unknown stage respectively. The treatment was two cycle of dual drug chemotherapy regimen including taxane plus platinum or fluorouracil combined with PD-1 antibody followed by tumor response assessment and surgery if the patient was eligible for resection. Results: Of the 28 patients, 1, 2, 3 and 4 cycles of chemotherapy combined with PD-1 antibody treatment completed in 1, 21, 5, and 1 patient, respectively. Objective response rate (ORR) was 71.4% (20/28), and disease control rate (DCR) was 100% (28/28). The incidence of adverse events exceeding grade 3 levels was 21.4% (6/28), including 3 neutropenia, 1 leukopenia, 1 thrombocytopenia and 1 immune hepatitis. There was no treatment-related death. Of the 23 patients underwent surgery, R0 resection rate was 87.0% (20/23), 13 patients had down staged to the T1-2N0M0 I stage, the pCR rate was 17.3% (4/23), and the pCR rate of primary tumor was 21.7% (5/23). Four patients received definitive chemoradiotherapy. One patient rejected surgery and other treatment after achieved PR response. Conclusion: Neoadjuvant chemotherapy combined PD-1 inhibitor is safe and has high efficacy in operable, borderline or potentially resectable locally advanced ESCC, and it is a promising regimen.

A Comparison of Palliative Radiotherapy Between 20 Gy in 5 Fractions and 30 Gy in 10 Fractions in Superior Vena Cava Syndrome Due to Carcinoma of Lung

A quasi-experimental study was conducted to compare palliative radiotherapy between 20 Gy in 5 fractions and 30 Gy in 10 fractions in superior vena cava syndrome due to carcinoma of lung. This study was done in National Institute of Cancer Research and Hospital (NICRH), Dhaka, Bangladesh, from September 2017 to August 2018. A total of 60 patients were enrolled in the study – 30 in each group. In Arm A, patients received 20 Gy in 5 fractions in 1 week, while in Arm B, patients received 30 Gy in 10 fractions in 2 weeks. Every patient was evaluated routinely to see the treatment outcome and toxicities. The mean age of Arm-A was 57.53±5.5 years and that of Arm-B was 57.40±5.4 years. After treatment, improvement of symptoms (e.g., edema, venous distension, dyspnea) of SVCS was observed. After 1 month of radiotherapy, complete resolution of venous distension occurred in majority of the patients (73.3% vs. 80%) and partial resolution occurred in rest of them (26.7% vs. 20%) in arms A and B respectively. Most of patients showed complete resolution of edema (83.3% vs. 86.7%), while few had partial resolution (16.7% vs. 13.3%) in arms A and B respectively. Symptoms of SVCS did not recur in any of the patients of both arms. Performance status also improved in all patients. Assessment of tumor response at the last follow-up showed partial response in 66.7% patients of Arm-A and 73.3% patients of Arm-B. Stable disease was observed in 33.3% patients of Arm-A and 26.7% patients of Arm-B. None of the patients showed disease progression. Toxicities included dysphagia (26.7% vs. 33.33%), fatigue (23.33% vs. 20%), nausea and vomiting (16.67% vs. 20%) and skin reaction (16.67% vs. 13.33%) in Arm-A and Arm-B respectively. All of those toxicities were grade-1 and easily controlled. There was no statistically significant difference between two treatment groups in terms of palliation of symptoms of SVCS, tumor response and toxicities. To summarize, although tumor response was not much satisfactory, both 20 Gy in 5 fractions and 30 Gy in 10 fractions are equally effective radiotherapy regimens in palliation of symptoms of SVCS due to lung cancer with tolerable toxicities. Hence, 20 Gy in 5 fractions can be a reasonable treatment choice in a resource-poor country like Bangladesh.
 CBMJ 2023 January: Vol. 12 No. 01 P: 33-40

The role of the multidisciplinary tumor board (MDTB) in the assessment of pancreatic cancer diagnosis and resectability: A tertiary referral center experience.

The introduction of multidisciplinary tumor boards (MDTBs) for the diagnostic and therapeutic pathway of several oncological disease significantly ameliorated patients' outcomes. However, only few evidences are currently present on the potential impact of the MDTB on pancreatic cancer (PC) management. Aim of this study is to report how MDTB may influence PC diagnosis and treatment, with particular focus on PC resectability assessment and the correspondence between MDTB definition of resectability and intraoperative findings. All patients with a proven or suspected diagnosis of PC discussed at the MDTB between 2018 and 2020 were included in the study. An evaluation of diagnosis, tumor response to oncological/radiation therapy and resectability before and after the MDTB was conducted. Moreover, a comparison between the MDTB resectability assessment and the intraoperative findings was performed. A total of 487 cases were included in the analysis: 228 (46.8%) for diagnosis evaluation, 75 (15.4%) for tumor response assessment after/during medical treatment, 184 (37.8%) for PC resectability assessment. As a whole, MDTB led to a change in treatment management in 89 cases (18.3%): 31/228 (13.6%) in the diagnosis group, 13/75 (17.3%) in the assessment of treatment response cohort and 45/184 (24.4%) in the PC resectability evaluation group. As a whole, 129 patients were given indication to surgery. Surgical resection was accomplished in 121 patients (93.7%), with a concordance rate of resectability between MDTB discussion and intraoperative findings of 91.5%. Concordance rate was 99% for resectable lesions and 64.3% for borderline PCs. MDTB discussion consistently influences PC management, with significant variations in terms of diagnosis, tumor response assessment and resectability. In this last regard, MDTB discussion plays a key role, as demonstrated by the high concordance rate between MDTB resectability definition and intraoperative findings.

Assessing the variability and correlation between SUV and ADC parameters of head and neck cancers derived from simultaneous PET/MRI: A single-center study.

Intratumoral heterogeneity is associated with poor outcomes in head and neck cancer (HNC) patients owing to chemoradiotherapy resistance. [18 F]-FDG positron emission tomography (PET) / Magnetic Resonance Imaging (MRI) provides spatial information about tumor mass, allowing intratumor heterogeneity assessment through histogram analysis. However, variability in quantitative PET/MRI parameter measurements could influence their reliability in assessing patient prognosis. Therefore, to use standardized uptake value (SUV) and apparent diffusion coefficient (ADC) parameters for assessing tumor response, this study aimed to measure SUV and ADC's variability and assess their relationship in HNC. First, ADC variability was measured in an in-house diffusion phantom and in five healthy volunteers. The SUV variability was only measured with the NEMA phantom using a clinical imaging protocol. Furthermore, simultaneous PET/MRI data of 11 HNC patients were retrospectively collected from the National Cyclotron and PET center in Chulabhorn Hospital. Tumor contours were manually drawn from PET images by an experienced nuclear medicine radiologist before tumor volume segmentation. Next, SUV and ADC's histogram were used to extract statistic variables of ADC and SUV: mean, median, min, max, skewness, kurtosis, and 5th , 10th , 25th , 50th , 75th , 90th , and 95th percentiles. Finally, the correlation between the statistic variables of ADC and SUV, as well as Metabolic Tumor volume and Total Lesion Glycolysis parameters was assessed using Pearson's correlation. This pilot study showed that both parameters' maximum coefficient of variation was 13.9% and 9.8% in the phantom and in vivo, respectively. Furthermore, we found a strong and negative correlation between SUVmax and ADVmed (r=-0.75, P=0.01). The SUV and ADC obtained by simultaneous PET/MRI can be potentially used as an imaging biomarker for assessing intratumoral heterogeneity in patients with HNC. The low variability and relationship between SUV and ADC could allow multimodal prediction of tumor response in future studies.

Diffusion-Weighted MRI in the Evaluation of Early-Stage Breast Cancer Treated with a Short Preoperative Radiotherapy: Preliminary Results.

To assess tumor response with diffusion-weighted MRI (DW-MRI) after a short preoperative radiotherapy in early-stage breast cancer (BCa). This was a prospective, single-center pilot study. 3T-MRI were performed before and after radiotherapy. The longest diameter (LD) and the apparent diffusion coefficient (ADC) value of a region of interest (ROI) of the tumors were recorded. Histopathology and immunohistochemistry, including the Ki-67 index of the core biopsy and of the surgical specimen, were the reference standards. Nineteen patients with 22 early-stage BCa were included. The mean ROI ADC value was 1.093 ± 0.278 × 10-3 mm2/s before radiotherapy and 1.490 ± 0.429 × 10-3 mm2/s (p-value < 0.001) after radiotherapy. The Ki-67 index was 9.2 ± 9.1% at the percutaneous biopsy before radiotherapy and 4.9 ± 7.5% (p-value = 0.005) after radiotherapy at the surgical specimen. After neoadjuvant radiotherapy, a 4.7% decrease in LD and a 36.3% increase in ROI-ADC of the tumors were measured at MRI and a 46.7% decrease in Ki-67 index was observed at histology of the surgical specimen in comparison with the percutaneous core biopsy. In early-stage BCa, a significant increase in ROI-ADC at DWI and a significant decrease in Ki-67 index were observed after a short preoperative radiotherapy, suggesting early tumor response.

Outcomes and Prognostic Factors for Locally Recurrent Rectal Cancer Treated With Proton Beam Therapy

Our objective was to report the outcome and prognostic factors for patients with locally recurrent rectal cancer (LRRC) treated with proton beam therapy (PBT) at our institution. The study included PBT-treated patients with LRRC between December 2008 and December 2019. Treatment response was stratified using an initial imaging test after PBT. Overall survival (OS), progression-free survival (PFS), and local control (LC) were estimated using the Kaplan-Meier method. Each outcome's prognostic factors were verified using the Cox proportional hazards model. Twenty-three patients were enrolled (median follow-up, 37.4 months). There were 11 patients with complete response (CR) or complete metabolic response (CMR), 8 with partial response or partial metabolic response, 2 with stable disease or stable metabolic response, and 2 with progressive disease or progressive metabolic disease. Three- and 5-year OS, PFS, and LC were 72.1% and 44.6%, 37.9% and 37.9%, and 55.0% and 47.2%, respectively, with 54.4 months' median survival time. The maximum standardized uptake value of fluorine-18-fluorodeoxyglucose-positron emission tomography-computed tomography (18F-FDG-PET/CT) before PBT (cutoff value, 10) showed significant differences in OS (P=.03), PFS (P=.027), and LC (P=.012). The patients who achieved CR or CMR after PBT had significantly better LC than those with non-CR or non-CMR (hazard ratio, 4.49; 95% confidence interval, 1.14-17.63; P=.021). Older patients (aged ≥65 years) had significantly higher LC and PFS rates. Patients with pain before PBT and larger tumors (≥30 mm) also had significantly lower PFS. Of 23 patients, 12 (52%) experienced further local recurrence after PBT. One patient developed grade 2 acute radiation dermatitis. Regarding late toxicity, grade 4 late gastrointestinal toxic effects were recorded in 3 patients, in 2 of whom reirradiation was associated with further local recurrence after PBT. The results showed that PBT may have potential to be a good treatment option for LRRC. 18F-FDG-PET/CT before and after PBT may be useful for assessing tumor response and predicting outcomes.

Changes in the tumor oxygenation but not in the tumor volume and tumor vascularization reflect early response of breast cancer to neoadjuvant chemotherapy

BackgroundBreast cancer neoadjuvant chemotherapy (NACT) allows for assessing tumor sensitivity to systemic treatment, planning adjuvant treatment and follow-up. However, a sufficiently large number of patients fail to achieve the desired level of pathological tumor response while optimal early response assessment methods have not been established now. In our study, we simultaneously assessed the early chemotherapy-induced changes in the tumor volume by ultrasound (US), the tumor oxygenation by diffuse optical spectroscopy imaging (DOSI), and the state of the tumor vascular bed by Doppler US to elaborate the predictive criteria of breast tumor response to treatment.MethodsA total of 133 patients with a confirmed diagnosis of invasive breast cancer stage II to III admitted to NACT following definitive breast surgery were enrolled, of those 103 were included in the final analysis. Tumor oxygenation by DOSI, tumor volume by US, and tumor vascularization by Doppler US were determined before the first and second cycle of NACT. After NACT completion, patients underwent surgery followed by pathological examination and assessment of the pathological tumor response. On the basis of these, data regression predictive models were created.ResultsWe observed changes in all three parameters 3 weeks after the start of the treatment. However, a high predictive potential for early assessment of tumor sensitivity to NACT demonstrated only the level of oxygenation, ΔStO2, (ρ = 0.802, p ≤ 0.01). The regression model predicts the tumor response with a high probability of a correct conclusion (89.3%). The “Tumor volume” model and the “Vascularization index” model did not accurately predict the absence of a pathological tumor response to treatment (60.9% and 58.7%, respectively), while predicting a positive response to treatment was relatively better (78.9% and 75.4%, respectively).ConclusionsDiffuse optical spectroscopy imaging appeared to be a robust tool for early predicting breast cancer response to chemotherapy. It may help identify patients who need additional molecular genetic study of the tumor in order to find the source of resistance to treatment, as well as to correct the treatment regimen.

Evaluation of the HD-GLIO Deep Learning Algorithm for Brain Tumour Segmentation on Postoperative MRI.

In the context of brain tumour response assessment, deep learning-based three-dimensional (3D) tumour segmentation has shown potential to enter the routine radiological workflow. The purpose of the present study was to perform an external evaluation of a state-of-the-art deep learning 3D brain tumour segmentation algorithm (HD-GLIO) on an independent cohort of consecutive, post-operative patients. For 66 consecutive magnetic resonance imaging examinations, we compared delineations of contrast-enhancing (CE) tumour lesions and non-enhancing T2/FLAIR hyperintense abnormality (NE) lesions by the HD-GLIO algorithm and radiologists using Dice similarity coefficients (Dice). Volume agreement was assessed using concordance correlation coefficients (CCCs) and Bland-Altman plots. The algorithm performed very well regarding the segmentation of NE volumes (median Dice = 0.79) and CE tumour volumes larger than 1.0 cm3 (median Dice = 0.86). If considering all cases with CE tumour lesions, the performance dropped significantly (median Dice = 0.40). Volume agreement was excellent with CCCs of 0.997 (CE tumour volumes) and 0.922 (NE volumes). The findings have implications for the application of the HD-GLIO algorithm in the routine radiological workflow where small contrast-enhancing tumours will constitute a considerable share of the follow-up cases. Our study underlines that independent validations on clinical datasets are key to asserting the robustness of deep learning algorithms.

Feasibility study of a Response Surveillance Program in locally advanced mid and low rectal cancer to increase organ preservation.

Assessment of tumor response in rectal cancer after neoadjuvant treatment by MRI (Tumour Regression Grade, TRG 1-5) is well standardized. The overall timing and method of defining complete response (cCR) remain controversial. The aim of this work was to evaluate the feasibility of a defined Response Surveillance Program (RSP) to increase organ preservation for locally advanced rectal cancer after neoadjuvant treatment. A standardized program of clinical (CR), radiological (RR) and metabolic (MR) assessment of tumor response is defined over a 6 month period from completion of NACRT with formal assessment performed every 2 months (M). Patients with TRG1-3at M2 and TRG1-2at M4 continue in the program up to M6 assessment. Patients managed with this protocol from 2016 to 2020 were analyzed. The primary endpoint was rectal preservation rate. Secondary endpoints included disease-free survival and overall survival at 3 years. 314 potentially suitable patients were enrolled in the RSP and 50 patients completed the six month program and were successfully enrolled into watch and wait. Fourteen (28%) were T2 tumor stage, 27 (54%) T3 and nine (18%) were T4. During watch and wait, patients with locoregional recurrence (n=11) were treated with local excision (n=3), endocavitary radiotherapy (n=1), TME (n=5) and APR (n=2). With a median follow-up of 32 months, the rectal preservation rate was 88%, with a 3-year disease-free survival of 67% and an overall survival of 98%. This study validates the feasibility of the practical implementation of a Response Surveillance Program to increase organ preservation rates without compromising oncological outcomes in rectal cancer.

Musculoskeletal immune-related adverse events in 927 patients treated with immune checkpoint inhibitors for solid cancer.

The prevalence of the musculoskeletal immune-related adverse events (irAEs) is probably underestimated, as most studies report only severe side effects. Our aim was to describe and characterize all musculoskeletal irAEs in a large cohort of patients treated with immune checkpoint inhibitors (ICI). We conducted a retrospective study among patients who received ICI from 07/27/2014 to 05/08/2020 at the medical oncology department of the Institut Paoli-Calmettes, Marseille, France. All medical files were systemically reviewed by a rheumatologist who collected clinical features, time of occurrence, treatment regimen, irAEs management, course and outcomes. We also assessed tumor response 3 months after introduction of ICI, according to severity and treatments used to manage musculoskeletal irAEs. Among 927 patients treated with ICI for a solid tumor, 118 patients (12.7%) presented a musculoskeletal irAE. Their median age was 66.5, 61% were male, and they mainly had a lung (57.6%) or urological cancer (27.1%). The most frequently involved ICI was an anti PD-1. Arthralgias and myalgias were the most frequent musculoskeletal irAEs (9.8%) and inflammatory rheumatic features were reported in 36 patients (3.9%) with elevated acute phase reactants and negative immunological markers. The median time of onset was 2 months (IC95% 1.8; 2.7). Tumor response at 3 months did not differ according to musculoskeletal irAE severity, type of manifestation (arthralgias/myalgias versus inflammatory rheumatic features), pain patterns (mechanical versus inflammatory) or irAE treatments. Musculoskeletal irAEs in this large cohort of patients treated with ICI were frequent (12.7%), mostly mild and well tolerated.

Tumor response assessment by measuring the single largest lesion per organ in advanced non-small cell lung cancer patients treated with PD-1/PD-L1 inhibitor.

For Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST1.1), measuring up to two target lesions per organ is an arbitrary criterion. We sought to compare response assessment using RECIST1.1 and modified RECIST1.1 (mRECIST1.1, measuring the single largest lesion per organ) in advanced non-small cell lung cancer (aNSCLC) patients undergoing anti-PD-1/PD-L1 monotherapy. Concordance of radiologic response categorization between RECIST1.1 and mRECIST1.1 was compared using the Kappa statistics. C-index was calculated to evaluate prognostic accuracy of radiologic response by the two criteria. The Kaplan-Meier method and Cox regression analysis were conducted for progression-free survival (PFS) and overall survival (OS). Eighty-seven patients who had at least two target lesions in any organ per the RECIST1.1 were eligible for comparison analysis. Tumor response showed excellent concordance when measured using the RECIST1.1 and mRECIST1.1 (Kappa = 0.961). C-index by these two criteria was similar for PFS (0.784 versus 0.785) and OS (0.649 versus 0.652). Responders had significantly longer PFS and OS versus non-responders (p < 0.05), whichever criterion adopted. Radiologic response remained a significant predictor of PFS and OS in multivariate analysis (p < 0.05). The mRECIST1.1 was comparable to RECIST1.1 in response assessment among aNSCLC patients who received single-agent PD-1/PD-L1 inhibitor. The mRECIST1.1, with reduced number of lesions to be measured, may be sufficient and more convenient to assess antitumor activity in clinical practice.

Interpretation of Rectal MRI after Neoadjuvant Treatment in Patients with Rectal Cancer

MRI is currently the imaging modality of choice to evaluate rectal cancer after neoadjuvant treatment. The purposes of restaging MRI are to assess the resectability of rectal cancer and to decide whether organ preservation strategies can be applied in patients with a complete clinical response. This review article indicates the key MRI features needed to evaluate rectal cancer after neoadjuvant treatment using a systematic approach. Assessment of primary tumor response including MRI findings to predict a complete response is discussed. Additionally, MRI evaluation of the relationship between the primary tumor and adjacent structures, lymph node response, extramural venous invasion, and tumor deposits after neoadjuvant treatment is presented. Knowledge of these imaging features and their clinical relevance may help radiologists provide an accurate and clinically valuable interpretation of restaging rectal MRI.

Estimating the Benefit of Preoperative Systemic Therapy to Reduce the Extent of Breast Cancer Surgery: Current Standard and Future Directions.

Once reserved for locally advanced tumors which were deemed inoperable at presentation, preoperative systemic therapy (PST) is nowadays increasingly used to treat early breast cancer. PST allows for in vivo assessment of tumor response, for tailoring of adjuvant systemic therapy and for de-escalation of breast and the axillary surgery. Increased rates of pathological complete response together with more accurate response assessment and surgical planning have led to a significant reduction in surgical morbidity. While surgical assessment remains the standard of care, ongoing studies are evaluating whether surgery can be omitted in patients who achieve a complete pathological response. In this chapter, I will review the impact of PST on surgical de-escalation and the data supporting the safety of this approach.