Primary cutaneous gamma/delta T-cell lymphoma in Taiwan: A series of six cases with frequent solitary presentation and relatively indolent behavior.

BACKGROUND: Primary cutaneous gamma/delta T-cell lymphoma (PCDG-TCL) is aggressive, frequently presenting as multiple plaques, tumors, and/or subcutaneous nodules. METHODS: In this study, we conducted a retrospective study in a tertiary center in Taiwan to characterize this rare tumor. RESULTS: We identified six patients. Five presented with a solitary lesion, including two with clinical impression of epidermal inclusion cyst or lipoma. Two of four evaluable cases exhibited epidermotropism, with one mimicking Pautrier microabscess. The neoplastic cells were pleomorphic and mostly medium- to large-sized. In all cases, the neoplastic cells expressed T-cell receptor (TCR)-γ and/or TCR-δ, with four co-expressing ßF1. Two of these ßF1+ cases co-expressed TCR-γ but not TCR-δ (two different clones). All were negative for Epstein-Barr virus (EBV), low stage, and treated with radiotherapy alone or combined chemotherapy and radiotherapy. In two patients, lymphoma relapsed in 3 and 7 months, respectively, and one patient died of the disease in 7 months. Four other patients were free of disease for 6 to 126 months. CONCLUSION: PCGD-TCL cases in Taiwan are more commonly solitary, frequently with indolent courses. The two currently available TCR-δ clones alone might be insufficient to detect all tumors.

Analysis of the pan-Asian subgroup of patients in the NALA Trial: a randomized phase III NALA Trial comparing neratinib+capecitabine (N+C) vs lapatinib+capecitabine (L+C) in patients with HER2+metastatic breast cancer (mBC) previously treated with two or more HER2-directed regimens.

PURPOSE: Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated systemic efficacy and intracranial activity in various stages of HER2+breast cancer. NALA was a phase III randomized trial that assessed the efficacy and safety of neratinib+capecitabine (N+C) against lapatinib+capecitabine (L+C) in HER2+ metastatic breast cancer (mBC) patients who had received ≥ 2 HER2-directed regimens. Descriptive analysis results of the Asian subgroup in the NALA study are reported herein. METHODS: 621 centrally assessed HER2+ mBC patients were enrolled, 202 of whom were Asian. Those with stable, asymptomatic brain metastases (BM) were eligible for study entry. Patients were randomized 1:1 to N (240 mg qd) + C (750 mg/m2 bid, day 1-14) with loperamide prophylaxis or to L (1250 mg qd) + C (1000 mg/m2 bid, day 1-14) in 21-day cycles. Co-primary endpoints were centrally assessed progression-free survival (PFS) and overall survival (OS). Secondary endpoints included time to intervention for central nervous system (CNS) disease, objective response rate, duration of response (DoR), clinical benefit rate, and safety. RESULTS: 104 and 98 Asian patients were randomly assigned to receive N+C or L+C, respectively. Median PFS of N+C and L+C was 7.0 and 5.4 months (P = 0.0011), respectively. Overall cumulative incidence of intervention for CNS disease was lower with N+C (27.9 versus 33.8%; P = 0.039). Both median OS (23.8 versus 18.7 months; P = 0.185) and DoR (11.1 versus 4.2 months; P < 0.0001) were extended with N+C, compared to L+C. The incidences of grade 3/4 treatment emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation were mostly comparable between the two arms. Diarrhea and palmar-plantar erythrodysesthesia were the most frequent TEAEs in both arms, similar to the overall population in incidence and severity. CONCLUSION: Consistent with the efficacy profile observed in the overall study population, Asian patients with HER2+ mBC, who had received ≥ 2 HER2-directed regimens, may also benefit from N+C. No new safety signals were noted. CLINICAL TRIAL REGISTRATION: NCT01808573.

Genomic Biomarkers of Survival in Patients with Adenocarcinoma of the Uterine Cervix Receiving Chemoradiotherapy.

This study investigated the prognostic effects of genomic biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma (AC) of the uterine cervix. In all, 21 patients receiving definitive CRT were included. In accordance with the International Federation of Gynecology and Obstetrics (FIGO) staging system, 5, 8, and 8 patients were classified as having stage IB3, II, and III disease, respectively. Pretreatment biomarkers were analyzed using tissue microarrays from biopsy specimens. Genomic alterations were examined by next-generation sequencing (NGS). The outcome endpoints were disease-free survival (DFS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS). A Cox regression model was used to examine the prognostic effects of the biomarkers and clinical parameters. The presence of myeloid cell leukemia-1 (MCL1) gene amplification and a lower immunohistochemical (IHC) marker of tumor necrotic factor alpha (TNF-α) H-score were two prognostic factors for inferior DFS. The four-year DFS was 28% and 68% for patients with or without MCL1 copy number gain, respectively (p = 0.028). In addition, MCL1 amplification predicted poor DMFS. A lower tumor mutation number (TMN) calculated from nonsynonymous mutations was associated with lower LRFS. For patients with adenocarcinoma of the uterine cervix receiving definitive CRT, prognostic information can be supplemented by MCL1 amplification, the TMN, and the TNF-α H score.

Prediction of local relapse and distant metastasis in patients with definitive chemoradiotherapy-treated cervical cancer by deep learning from [18F]-fluorodeoxyglucose positron emission tomography/computed tomography.

BACKGROUND: We designed a deep learning model for assessing 18F-FDG PET/CT for early prediction of local and distant failures for patients with locally advanced cervical cancer. METHODS: All 142 patients with cervical cancer underwent 18F-FDG PET/CT for pretreatment staging and received allocated treatment. To augment the amount of image data, each tumor was represented as 11 slice sets each of which contains 3 2D orthogonal slices to acquire a total of 1562 slice sets. In each round of k-fold cross-validation, a well-trained proposed model and a slice-based optimal threshold were derived from a training set and used to classify each slice set in the test set into the categories of with or without local or distant failure. The classification results of each tumor were aggregated to summarize a tumor-based prediction result. RESULTS: In total, 21 and 26 patients experienced local and distant failures, respectively. Regarding local recurrence, the tumor-based prediction result summarized from all test sets demonstrated that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 71%, 93%, 63%, 95%, and 89%, respectively. The corresponding values for distant metastasis were 77%, 90%, 63%, 95%, and 87%, respectively. CONCLUSION: This is the first study to use deep learning model for assessing 18F-FDG PET/CT images which is capable of predicting treatment outcomes in cervical cancer patients. KEY POINTS: • This is the first study to use deep learning model for assessing 18 F-FDG PET/CT images which is capable of predicting treatment outcomes in cervical cancer patients. • All 142 patients with cervical cancer underwent 18 F-FDG PET/CT for pretreatment staging and received allocated treatment. To augment the amount of image data, each tumor was represented as 11 slice sets each of which contains 3 2D orthogonal slices to acquire a total of 1562 slice sets. • For local recurrence, all test sets demonstrated that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 71%, 93%, 63%, 95%, and 89%, respectively. The corresponding values for distant metastasis were 77%, 90%, 63%, 95%, and 87%, respectively.

[18]Fluorodeoxyglucose Positron Emission Tomography for the Textural Features of Cervical Cancer Associated with Lymph Node Metastasis and Histological Type.

BACKGROUND: In this study, we investigated the correlation between the lymph node (LN) status or histological types and textural features of cervical cancers on 18F-fluorodeoxyglucose positron emission tomography/computed tomography. METHODS: We retrospectively reviewed the imaging records of 170 patients with International Federation of Gynecology and Obstetrics stage IB-IVA cervical cancer. Four groups of textural features were studied in addition to the maximum standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis (TLG). Moreover, we studied the associations between the indices and clinical parameters, including the LN status, clinical stage, and histology. Receiver operating characteristic curves were constructed to evaluate the optimal predictive performance among the various textural indices. Quantitative differences were determined using the Mann-Whitney U test. Multivariate logistic regression analysis was performed to determine the independent factors, among all the variables, for predicting LN metastasis. RESULTS: Among all the significant indices related to pelvic LN metastasis, homogeneity derived from the gray-level co-occurrence matrix (GLCM) was the sole independent predictor. By combining SUVmax, the risk of pelvic LN metastasis can be scored accordingly. The TLGmean was the independent feature of positive para-aortic LNs. Quantitative differences between squamous and nonsquamous histology can be determined using short-zone emphasis (SZE) from the gray-level size zone matrix (GLSZM). CONCLUSION: This study revealed that in patients with cervical cancer, pelvic or para-aortic LN metastases can be predicted by using textural feature of homogeneity from the GLCM and TLGmean, respectively. SZE from the GLSZM is the sole feature associated with quantitative differences between squamous and nonsquamous histology.

Correlation of pretreatment 18F-FDG PET tumor textural features with gene expression in pharyngeal cancer and implications for radiotherapy-based treatment outcomes.

PURPOSE: This study investigated the correlation of the matrix heterogeneity of tumors on 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) with gene-expression profiling in patients with pharyngeal cancer and determined the prognostic factors for radiotherapy-based treatment outcomes. METHODS: We retrospectively reviewed the records of 57 patients with stage III-IV oropharyngeal or hypopharyngeal cancer who had completed definitive therapy. Four groups of the textural features as well as 31 indices were studied in addition to maximum standard uptake value, metastatic tumor volume, and total lesion glycolysis. Immunohistochemical data from pretreatment biopsy specimens (Glut1, CAIX, VEGF, HIF-1α, EGFR, Ki-67, Bcl-2, CLAUDIN-4, YAP-1, c-Met, and p16) were analyzed. The relationships between the indices and genomic expression were studied, and the robustness of various textural features relative to cause-specific survival and primary relapse-free survival was analyzed. RESULTS: The overexpression of VEGF was positively associated with the increased values of the matrix heterogeneity obtained using gray-level nonuniformity for zone (GLNUz) and run-length nonuniformity (RLNU). Advanced T stage (p = 0.01, hazard ratio [HR] = 3.38), a VEGF immunoreactive score of >2 (p = 0.03, HR = 2.79), and a higher GLNUz value (p = 0.04, HR = 2.51) were prognostic factors for low cause-specific survival, whereas advanced T stage, a HIF-1α staining percentage of ≥80%, and a higher GLNUz value were prognostic factors for low primary-relapse free survival. CONCLUSIONS: The overexpression of VEGF was associated with the increased matrix index of GLNUz and RLNU. For patients with pharyngeal cancer requiring radiotherapy, the treatment outcome can be stratified according to the textural features, T stage, and biomarkers.

Lymphoma in Taiwan: Review of 1347 neoplasms from a single institution according to the 2016 Revision of the World Health Organization Classification.

BACKGROUND/PURPOSE: Lymphoid neoplasms are heterogeneous and types of lymphoma vary in different geographic regions. In this study, we aimed at classifying the lymphoid neoplasms at our institution in Taiwan and to compare the relative frequency of various types of lymphoma in different countries. METHODS: We retrospectively searched the files of patients diagnosed with lymphoma at our institution from 2000 to 2015 based on the 2016 Revision of the World Health Organization classification. RESULTS: We identified 1339 patients with lymphoid neoplasms; among them, eight had two distinct types of lymphoid neoplasms. Of the 1347 neoplasms, 6.09% were Hodgkin lymphomas (HLs) and 93.31%, non-HL (NHLs). Among the 1257 NHLs, 82.66% were of B-cell lineage and 17.34% of T-cell lineage. The most common B-cell lymphoma types were diffuse large B-cell lymphoma, follicular lymphoma, and mucosa-associated lymphoid tissue lymphoma. Among T-cell neoplasms, 37% cases were of nodal origin and 63% cases arose in extranodal sites. The most common nodal and extranodal T-cell neoplasms were angioimmunoblastic T-cell lymphoma and extranodal natural killer/T-cell lymphoma, nasal type, respectively. CONCLUSION: We analyzed the largest series of lymphomas to date from Taiwan and concluded that HL was rare and T-cell neoplasms comprised around 17% of all NHLs in Taiwan. The relative frequency of the major lymphoma types is similar in East Asian countries, with only a minor difference, but the overall pattern in the East is quite different from that in the West, with the latter showing a higher frequency of HL and a lower rate of T-cell neoplasms.

Immunohistochemical overexpression of hypoxia-induced factor 1α associated with slow reduction in 18fluoro-2-deoxy-D-glucose uptake for chemoradiotherapy in patients with pharyngeal cancer.

BACKGROUND: This study examined genomic factors associated with a reduction in 18fluoro-2-deoxy-D-glucose (FDG) uptake during positron emission tomography-computed tomography (PET-CT) for definitive chemoradiotherapy (CRT) in patients with pharyngeal cancer. METHODS: The pretreatment and interim PET-CT images of 25 patients with advanced pharyngeal cancers receiving definitive CRT were prospectively evaluated. The maximum standardized uptake value (SUVmax) of the interim PET-CT and the reduction ratio of the SUVmax (SRR) between the two images were measured. Genomic data from pretreatment incisional biopsy specimens (SLC2A1, CAIX, VEGF, HIF1A, BCL2, Claudin-4, YAP1, MET, MKI67, and EGFR) were analyzed using tissue microarrays. Differences in FDG uptake and SRRs between tumors with low and high gene expression were examined using the Mann-Whitney test. Cox regression analysis was performed to examine the effects of variables on local control. RESULTS: The SRR of the primary tumors (SRR-P) was 0.59 ± 0.31, whereas the SRR of metastatic lymph nodes (SRR-N) was 0.54 ± 0.32. Overexpression of HIF1A was associated with a high iSUVmax of the primary tumor (P < 0.001) and neck lymph node (P = 0.04) and a low SRR-P (P = 0.02). Multivariate analysis revealed that patients who had tumors with low SRR-P or high HIF1A expression levels showed inferior local control. CONCLUSION: In patients with pharyngeal cancer requiring CRT, HIF1A overexpression was positively associated with high interim SUVmax or a slow reduction in FDG uptake. Prospective trials are needed to determine whether the local control rate can be stratified using the HIF1A level as a biomarker and SRR-P.

Immunophenotypic and genetic characteristics of diffuse large B-cell lymphoma in Taiwan.

BACKGROUND/PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma type. The immunophenotypic and genetic features of DLBCL in Taiwan have not been characterized. METHODS: In this study, we performed immunohistochemical analysis and interphase fluorescence in situ hybridization (FISH) using tissue microarray sections to investigate a cohort of unselected DLBCL cases in a single institution in Taiwan from 1990 to 2010. RESULTS: Of the 153 cases investigated, CD10, bcl-6, and MUM1 were expressed in 16.3%, 71.2%, and 71.9% cases, respectively, with 27.5% (n = 42) of cases being classified as having a germinal center B-cell (GCB) origin by the Hans algorithm. By FISH analysis, 19.6%, 4.6%, 26.1%, and 3.9% cases showed rearrangement at IGH, BCL2, BCL6, and MYC loci, respectively, including three (2.0%) cases of double-hit lymphoma. As compared with the non-GCB tumors, GCB tumors more frequently expressed CD10 (p < 0.001) and bcl-6 (p = 0.001) with less frequent expression of MUM1 (p = 0.007). Moreover, GCB tumors more frequently exhibited rearrangement at the BCL2 (p = 0.024) and MYC (p = 0.038) loci than non-GCB tumors. However, there was no survival difference between these two groups. CONCLUSION: In this first series of DLBCL evaluation from Taiwan, we found that the relative frequency of GCB tumors among DLBCL was low in most East Asian countries. There is a wide range of BCL2 rearrangement rates, higher in the West and lower in East Asia. A larger and/or national study is warranted to better understand the immunophenotypic and molecular features of DLBCL in Taiwan and their respective impact on patient survival.

Low-dose, prophylactic, extended-field, intensity-modulated radiotherapy plus concurrent weekly cisplatin for patients with stage IB2-IIIB cervical cancer, positive pelvic lymph nodes, and negative para-aortic lymph nodes.

OBJECTIVE: The objective of this study was to assess prospectively the clinical outcomes of low-dose prophylactic extended-field, intensity-modulated radiotherapy (IMRT) plus concurrent weekly cisplatin for patients with stage IB2-IIIB cervical cancer, positive pelvic lymph nodes (PLNs), and negative para-aortic lymph nodes (PALNs). METHODS: Thirty-two patients with stage IB2-IIIB cervical cancer with positive PLN and negative PALN were included prospectively. All lymph nodes were assessed with positron emission tomography. The PALN field, including lymphatics from the superior border of L1 to the L4-L5 interphase, was irradiated concurrently with pelvic IMRT with a prescribed dose of 40 Gy in 25 fractions. Chemotherapy consisted of cisplatin delivered weekly at a dose of 40 mg/m. Using historical controls treated with pelvic radiotherapy, the survival curves were compared to assess the difference between the 2 treatment periods. RESULTS: Thirty-one patients completed the allocated extended-field IMRT, and all finished the planned pelvic IMRT and brachytherapy. Acute ≥ grade 3 gastrointestinal, genitourinary, and hematologic toxicities were seen in 2, 1, and 18 patients, respectively. During a median follow-up of 33 months, 5 patients developed out-field distant recurrences. One patient had a late grade 3 gastrointestinal complication, and 1 patient had genitourinary toxicity. The 3-year actuarial overall survival, disease-free survival, and distant metastasis-free survival for the study cohort and historic controls were 87% versus 62% (P = 0.02), 82% versus 54% (P = 0.02), and 79% versus 57% (P = 0.01), respectively. CONCLUSIONS: Extended-field IMRT of 40 Gy to the PALN plus concurrent cisplatin can effectively eradicate subclinical disease at the PALN and improve the outcome for patients with PLN-positive stage IB2-IIIB cervical cancer.

Early prediction of distant metastasis in patients with uterine cervical cancer treated with definitive chemoradiotherapy by deep learning using pretreatment [ 18 F]fluorodeoxyglucose positron emission tomography/computed tomography.

OBJECTIVES: A deep learning (DL) model using image data from pretreatment [ 18 F]fluorodeoxyglucose ([ 18 F] FDG)-PET or computed tomography (CT) augmented with a novel imaging augmentation approach was developed for the early prediction of distant metastases in patients with locally advanced uterine cervical cancer. METHODS: This study used baseline [18F]FDG-PET/CT images of newly diagnosed uterine cervical cancer patients. Data from 186 to 25 patients were analyzed for training and validation cohort, respectively. All patients received chemoradiotherapy (CRT) and follow-up. PET and CT images were augmented by using three-dimensional techniques. The proposed model employed DL to predict distant metastases. Receiver operating characteristic (ROC) curve analysis was performed to measure the model's predictive performance. RESULTS: The area under the ROC curves of the training and validation cohorts were 0.818 and 0.830 for predicting distant metastasis, respectively. In the training cohort, the sensitivity, specificity, and accuracy were 80.0%, 78.0%, and 78.5%, whereas, the sensitivity, specificity, and accuracy for distant failure were 73.3%, 75.5%, and 75.2% in the validation cohort, respectively. CONCLUSION: Through the use of baseline [ 18 F]FDG-PET/CT images, the proposed DL model can predict the development of distant metastases for patients with locally advanced uterine cervical cancer treatment by CRT. External validation must be conducted to determine the model's predictive performance.

Incidence of pneumonia and risk factors among patients with head and neck cancer undergoing radiotherapy.

BACKGROUND: This study investigated the incidence and patient- and treatment-related risk factors related to pneumonia acquired during radiotherapy (PNRT) in head and neck cancer (HNC) patients. METHODS: Using the universal insurance claims data, 15,894 total HNC patients between 1998 and 2007 were included in this analysis. PNRT was defined as the occurrence of pneumonia within 90 days of the commencement of radiotherapy. Information also included some demographic characteristics, treatment-related factors, and comorbidities. Appropriate statistical tests were performed to assess the difference between patients with and those without PNRT. A logistic regression was used to estimate the odds ratio (OR) of PNRT among the variables examined. RESULTS: In total, 772 patients (4.86%) were identified with PNRT as the case group, whereas 15,122 subjects of the same cancer without PNRT formed the control group. Of patients with PNRT, 632 (81.9%) were hospitalized with a mean length of stay of 25.9 days. Results from the multiple logistic regression showed that an older age and certain comorbidities were associated with an increased risk of PNRT. Patients with cancer of the tongue, buccal mucosa, oropharynx, and hypopharynx/larynx were at particularly higher risk (OR = 1.28, 1.28, 1.67, and 1.74, respectively). Compared to radiotherapy alone, concurrent chemoradiotherapy had no effect on the PNRT. Patients in the PNRT group had higher overall medical costs and length of stay. CONCLUSION: The incidence of PNRT in HNC patients receiving radiotherapy was approximately 5%. Notably, an older age, certain comorbidities, and certain specific tumor sites were associated with an increased risk.

Does initial 45Gy of pelvic intensity-modulated radiotherapy reduce late complications in patients with locally advanced cervical cancer? A cohort control study using definitive chemoradiotherapy with high-dose rate brachytherapy.

BACKGROUND: Comparing initial 45 Gy of pelvic intensity-modulated radiation therapy (IMRT) and non-IMRT in terms of the late toxicities associated with advanced cervical cancer that has also been treated with definitive concurrent chemoradiotherapy and high-dose rate intracavitary brachytherapy (HDRICB). PATIENTS AND METHODS: This retrospective study included 320 stage IB2-IIIB cervical cancer patients treated with CCRT (83 IMRT and 237 non-IMRT). The two groups had similar stage and HDRICB ratings. Following 45 Gy to the pelvis, HDRICB of 24 Gy in four courses was prescribed. Late toxicities, including rectal complications (RC), bladder complications (BC) and non-rectal intestinal injury (NRRII), were scored by the Common Terminology Criteria for Adverse Events. A logistic regression was used to estimate the odds ratio (OR) of the complications. RESULTS: With a median follow-up duration of 33 and 77 months for IMRT and non-IMRT, 33 patients had Grade 2 or higher late RC (7.2% IMRT, 11.4% non-IMRT), whereas that for BC was 40 (9.6% IMRT, 13.5% non-IMRT) and for NRRII was 48 (12.0% IMRT, 16.0% non-IMRT). The cumulative rate for total grade 3 or higher gastrointestinal or genitourinary toxicities was 8.4% and 11.8% (p = 0.33). IMRT did not reduce the OR for all endpoints; however, the ORs for rectum and bladder reference doses to Point A were associated with RC and BC. CONCLUSIONS: Locally advanced cervical cancer patients treated with initial 45Gy of pelvic IMRT and HDRICB have similar treatment-related late toxicities as those treated with non-IMRT. Optimization of the brachytherapy scheme is essential to minimize late toxicities.

Image-guided brachytherapy following external-beam radiation therapy for patients with inoperable endometrial cancer.

OBJECTIVE: To investigate the outcomes of definitive external-beam radiation therapy (EBRT) plus image-guided brachytherapy (IGBT) in patients with endometrial cancer (EC) unsuitable for surgery. METHODS: A total of 50 patients with inoperable EC were included. The patients received EBRT in a median dose of 45 Gy to the pelvis over 5 weeks. Thereafter, the patients received brachytherapy using tandem and ovoid applicators. High-risk clinical target volume (HR-CTV) and gross tumor volume in brachytherapy (GTVp) were defined by the assistance of patients' pre-IGBT magnetic resonance imaging. RESULTS: The medical records of the 50 patients were analyzed. The main causes of inoperability were anesthesia contraindications, namely medical comorbidities and obesity. The median cumulative D90s (the minimum dose delivered to 90% of the volume) in EQD2 (equivalent dose in 2-Gy fractions) to the HR-CTV and GTVp were 72.9 Gy10 (range, 64.9 to 80.3) and 166.2 Gy10 (range, 123.0 to 189.8), respectively. Over a median follow-up period of 27 months, 8 of the patients died of cancer. The 2-year overall and cancer-specific survival rates were 75% and 83%, respectively. The cumulative incidences of pelvic and distant failure were 4% (n = 2) and 16% (n = 8), respectively. Gastrointestinal complications of grade 2 or above were noted in 2 patients (4%), and a grade 2 genitourinary complication was noted in one. CONCLUSIONS: For patients with inoperable EC, EBRT followed by IGBT is an effective approach for achieving high local control without a high risk of complications.

Imaging prediction of KRAS mutation in patients with rectal cancer through deep metric learning using pretreatment [18F]Fluorodeoxyglucose positron emission tomography/computed tomography.

OBJECTIVES: To predict KRAS mutation in rectal cancer (RC) through computer vision of [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) by using metric learning (ML). METHODS: This study included 160 patients with RC who had undergone preoperative PET/CT. KRAS mutation was identified through polymerase chain reaction analysis. This model combined ML with the deep-learning framework to analyze PET data with or without CT images. The Batch Balance Wrapper framework and K-fold cross-validation were employed during the learning process. A receiver operating characteristic (ROC) curve analysis was performed to assess the model's predictive performance. RESULTS: Genetic alterations in KRAS were identified in 82 (51%) tumors. Both PET and CT images were used, and the proposed model had an area under the ROC curve of 0.836 for its ability to predict a mutation status. The sensitivity, specificity, and accuracy were 75.3%, 79.3%, and 77.5%, respectively. When PET images alone were used, the area under the curve was 0.817, whereas the sensitivity, specificity, and accuracy were 73.2%, 79.6%, and 76.2%, respectively. CONCLUSIONS: The ML model presented herein revealed that baseline 18F-FDG PET/CT images could provide supplemental information to determine KRAS mutation in RC. Additional studies are required to maximize the predictive accuracy. ADVANCES IN KNOWLEDGE: The results of the ML model presented herein indicate that baseline 18F-FDG PET/CT images could provide supplemental information for determining KRAS mutation in RC.The predictive accuracy of the model was 77.5% when both image types were used and 76.2% when PET images alone were used. Additional studies are required to maximize the predictive accuracy.

Effectiveness of Stereotactic Ablative Radiotherapy for Systemic Therapy Respondents with Inoperable Pulmonary Oligometastases and Oligoprogression.

Stereotactic ablative radiotherapy (SABR) may improve survival in patients with inoperable pulmonary oligometastases. However, the impact of pulmonary oligometastatic status after systemic therapy on SABR outcomes remains unclear. Hence, we investigated the outcomes of SABR in 45 patients with 77 lung tumors and the prognostic value of pulmonary oligoprogression. Eligibility criteria were pulmonary oligometastases (defined as ≤5 metastatic lung tumors), controlled extrapulmonary disease (EPD) after front-line systemic therapy, SABR as primary local treatment for inoperable pulmonary metastases, and consecutive imaging follow-up. Oligometastatic lung tumor was classified into controlled or oligoprogressive status. Overall survival (OS), in-field progression-free survival (IFPFS), out-field progression-free survival (OFPFS), and prognostic variables were evaluated. With 21.8 months median follow-up, the median OS, IFPFS, and OFPFS were 28.3, not reached, and 6.5 months, respectively. Two-year OS, IFPFS, and OFPFS rates were 56.0%, 74.2%, and 17.3%, respectively. Oligoprogressive status (p = 0.003), disease-free interval < 24 months (p = 0.041), and biologically effective dose (BED10) < 100 Gy (p = 0.006) were independently associated with inferior OS. BED10 ≥ 100 Gy (p = 0.029) was independently correlated with longer IFPFS. Oligoprogressive status (p = 0.017) and EPD (p = 0.019) were significantly associated with inferior OFPFS. Grade ≥ 2 radiation pneumonitis occurred in four (8.9%) patients. Conclusively, SABR with BED10 ≥ 100 Gy could provide substantial in-field tumor control and longer OS for systemic therapy respondents with inoperable pulmonary oligometastases. Oligoprogressive lung tumors exhibited a higher risk of out-field treatment failure and shorter OS. Hence, systemic therapy should be tailored for patients with oligoprogression to reduce the risk of out-field treatment failure. However, in the absence of effective systemic therapy, SABR is a reasonable alternative to reduce resistant tumor burden.

Use of pretreatment metabolic tumour volumes to predict the outcome of pharyngeal cancer treated by definitive radiotherapy.

PURPOSE: The aim of the study was to investigate the predictive role of pretreatment metabolic volume (MTV) in pharyngeal cancer (PC) patients treated with definitive (chemo) radiotherapy. METHODS: This retrospective analysis enrolled 64 patients with PC treated with (chemo) radiotherapy. All patients received pretreatment fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. Four PET segmentation methods were used, namely applying an isocontour at a standardized uptake value (SUV) of either 2.5 or 3.0 (MTV2.5 and MTV3.0) or using fixed thresholds of either 40 or 50 % (MTV40 %, MTV50 %) of the maximum intratumoural FDG activity. Disease-free survival (DFS) and primary relapse-free survival (PRFS) were examined according to cutoffs of the median values for each MTV and the gross tumour volume (GTVp). Independent prognosticators were identified by Cox regression analysis. RESULTS: With a median follow-up of 24 months, 19 patients died, and 26 patients experienced tumour relapse at primary sites. Multivariate analysis of the DFS showed that MTV2.5 > 13.6 ml was the only predictor of relapse [p = 0.011, hazard ratio = 2.69, 95 % confidence interval (CI) 1.25-5.76]. The independent predictor for PRFS was MTV2.5 > 13.6 ml (p = 0.003, hazard ratio = 3.76, 95 % CI 1.57-8.92), whereas GTVp > 15.5 ml had a marginal impact on PRFS (p = 0.06, hazard ratio = 3.54, 95 % CI 0.97-11.85). Patients having tumours with MTV2.5 > 13.6 ml had a significantly inferior 2-year PRFS compared with patients who had lower MTV2.5 tumours (39 vs 72 %, respectively, p = 0.001). CONCLUSION: For PC patients treated with definitive (chemo)radiotherapy, pretreatment MTV2.5 volume achieved the best predictive value for primary recurrence, and the same value was also a prognosticator for DFS.

Neck Lymph Node Recurrence in HNC Patients Might Be Predicted before Radiotherapy Using Radiomics Extracted from CT Images and XGBoost Algorithm.

The five-year overall survival rate of patients without neck lymph node recurrence is over 50% higher than those with lymph node metastasis. This study aims to investigate the prognostic impact of computed tomogram (CT)-based radiomics on the outcome of metastatic neck lymph nodes in patients with head and neck cancer (HNC) receiving definitive radiotherapy or chemoradiotherapy for organ preservation. The pretreatment 18F-FDG PET/CT of 79 HNC patients was retrospectively analyzed with radiomics extractors. The imbalanced data was processed using two techniques: over-sampling and under-sampling, after which the prediction model was established with a machine learning model using the XGBoost algorithm. The imbalanced dataset strategies slightly decreased the specificity but greatly improved the sensitivity. To have a higher chance of predicting neck cancer recurrence, however, clinical data combined with CT-based radiomics provides the best prediction effect. The original dataset performed was as follows: accuracy = 0.76 ± 0.07, sensitivity = 0.44 ± 0.22, specificity = 0.88 ± 0.06. After we used the over-sampling technique, the accuracy, sensitivity, and specificity values were 0.80 ± 0.05, 0.67 ± 0.11, and 0.84 ± 0.05, respectively. Furthermore, after using the under-sampling technique, the accuracy, sensitivity, and specificity values were 0.71 ± 0.09, 0.73 ± 0.13, and 0.70 ± 0.13, respectively. The outcome of metastatic neck lymph nodes in patients with HNC receiving radiotherapy for organ preservation can be predicted based on the results of machine learning. This way, patients can be treated alternatively. A further external validation study is required to verify our findings.

Distinctive patterns of marrow involvement by classic Hodgkin lymphoma are clues for diagnosis and subtyping.

Classic Hodgkin lymphoma (CHL) is a lymphoid neoplasm deriving from B cells in a rich inflammatory background. There are four histological subtypes with different epidemiological features. Bone marrow involvement by CHL is infrequent, and subtyping CHL from the bone marrow is not suggested as there might be discordant histopathology between the primary tumors and bone marrow specimens. In this study, we aimed to identify the histopathological features of bone marrow involved by CHL and tried to correlate these features with their subtypes. Among the 23 recruited cases, the frequencies of mixed cellularity (MC; 48%, 11/23) and nodular sclerosis (NS; 44%, 10/23) were similar. There were two patterns of marrow involvement: pattern A (fibrous), space-occupying lesions with alternating hypo- and hypercellular areas against a fibrotic background with dilated sinusoids and pattern B (histiocyte-rich), ill-defined granuloma-like lesions in which histiocytes merged with normal hematopoietic and inflammatory cells. Pattern A was more frequent in patients with CHL-NS than CHL-MC (100% vs. 18.2%; p < 0.001). Diagnostic Hodgkin cells and Reed-Sternberg (HRS) cells were identified in all cases, while HRS variant lacunar cells were occasionally discovered, particularly in the CHL-NS subtype (NS 100% vs. MC 9%; p < 0.001). The frequency of EBV association was higher in MC (64%) than that in NS (36%) subtype, but not statistically significant. Of the two patterns of marrow involvement, pattern A was more commonly associated with the NS subtype and less frequently associated with EBV. Recognizing the patterns of marrow involvement is important for diagnosis and may contribute to the subtyping of CHL.

Role of high ubiquitin-conjugating enzyme E2 expression as a prognostic factor in nasopharyngeal carcinoma.

The incidence of nasopharyngeal carcinoma (NPC) in Southeast Asia and Taiwan is high due to epidemiological factors. Cisplatin-based chemoradiotherapy is an important treatment strategy with excellent outcomes for patients with NPC. However, the outcomes for patients who are refractory to cisplatin-based therapy are poor. Methods for risk stratification of patients with NPC undergoing cisplatin-based chemoradiotherapy require to be investigated. A previous study indicated that ubiquitin-conjugating enzyme E2 B (UBE2B) was able to regulate alkylating drug sensitivity in NPC cells. In the present study, the clinical significance of UBE2B expression in patients with NPC was analyzed. Analysis of the two available NPC datasets containing the UBE2B expression profile (GSE12452 and GSE68799) was performed to evaluate the UBE2B expression levels in NPC tissues compared with nasopharyngeal mucosal epithelial tissues. Furthermore, immunohistochemical staining was performed using anti-UBE2B antibodies on samples from 124 patients with NPC who underwent cisplatin-based chemoradiotherapy. Disease-specific survival (DSS), distant metastatic-free survival (DMeFS) and local recurrence-free survival (LRFS) of patients with high and low UBE2B expression was analyzed. Furthermore, the associations between UBE2B expression and the biological behavior of NPC cells were investigated in vitro. Using public NPC datasets and in vitro studies, it was identified that UBE2B expression levels were increased in NPC tumor tissues compared with those in mucosal epithelial tissues. The cell proliferation ability was decreased in UBE2B-deficient NPC cells as compared with that in UBE2B-proficient cells. Immunohistochemical analysis of 124 NPC tissues from patients who underwent cisplatin-based chemoradiotherapy indicated that high UBE2B expression levels were associated with poor DSS, DMeFS and LRFS. Multivariate regression analysis of factors influencing survival also confirmed that high UBE2B expression levels were a statistically significant independent risk factor for poor clinical outcomes in terms of DSS [hazard ratio (HR), 1.955; 95% CI 1.164-3.282], DMeFS (HR, 2.141; 95% CI 1.206-3.801) and LRFS (HR, 2.557; 95 CI 1.313-4.981). In vitro analysis indicated that O6-methylguanine-DNA methyltransferase attenuated cisplatin sensitivity induced by knockdown of UBE2B in NPC cells. In conclusion, the present study demonstrated that high UBE2B expression is associated with poor clinical outcomes for patients with NPC treated with cisplatin-based chemoradiotherapy.