Longest Diameter Research Articles

Impact of CT-assessed changes in tumor size after neoadjuvant chemotherapy on pathological response and survival of patients with esophageal squamous cell carcinoma.

Neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for advanced esophageal squamous cell carcinoma (ESCC) in Japan. Computed tomography (CT) is usually used to assess the therapeutic effect of NAC; however, there are no reliable criteria for predicting pathological response or patient prognosis. We included 84 patients who underwent esophagectomy between January 2009 and December 2018 and retrospectively reviewed their CT scans performed before and after NAC. The reduction rate of the largest tumor area (TA), long diameter (LD), and short diameter (SD) were measured on a transverse CT image. The pathological response and cutoff values were calculated using the receiver operating characteristic curve, and the most suitable ones for determining the effect were examined. The areas under the curve for predicting responders to NAC based on the reduction rate of the TA, LD, and SD were 0.755, 0.761, and 0.781, respectively. The optimal cutoff value of the SD reduction rate for predicting responders to NAC was 22%. An SD reduction ≥ 22% was an independent prognostic factor for overall survival in univariate (p = 0.005, hazard ratio [HR] = 2.755) and multivariate analyses (p = 0.030 HR 2.690). Furthermore, an SD reduction of ≥ 22% was also an independent prognostic factor for relapse-free survival in the univariate (p = 0.007, HR = 2.491) and multivariate analyses (p = 0.007, HR = 0.030). The reduction rate of the tumor SD is a simple predictor of pathological response and patient prognosis.

Predictive Factors of Late Cervical Lymph Node Metastasis Using Intraoral Sonography in Patients With Tongue Cancer.

The objective of this study was to investigate the predictive factors of late cervical lymph node metastasis in patients with tongue cancer, based on the intraoral ultrasonographic (IUS) findings of the primary tongue lesion. Patients with T1/2N0M0 primary tongue cancer (n=106) were examined using IUS between September 2014 and September 2020. The relationships between the incidence of late cervical lymph node metastasis with the longest diameter, thickness, margin type, internal echo intensity, and internal or peripheral vascularity of the tongue lesion on Doppler IUS were assessed. Multivariate analysis indicated that irregular margins of the lesion and the presence of internal echo intensity were significantly related to the incidence of late cervical lymph node metastasis. Irregular margins and internal echo intensity of the tongue cancer lesion assessed using IUS may predict the occurrence of late cervical lymph node metastasis in T1/2N0M0 cases.

Natural speed of growth of untreated soft-tissue sarcomas: A dimension-based imaging analysis

PurposeThe interval from first symptoms to diagnosis, staging and referral to reference center can last months for soft-tissue sarcoma (STS) patients. Meanwhile, patients can undergo different imaging that capture the ‘natural’ tumor changes, before medical intervention. Aim was to depict these ‘natural’ dimensional variations and to correlate them with patients’ outcome. MethodsSingle-center retrospective study including all consecutive adults with newly-diagnosed STS, ≥2 pre-treatment imaging (CT-scan or MRI) on the tumor (Exam-0 and Exam-1), and managed in reference center between 2007 and 2018. Longest diameter (LD) and volume were calculated on both examinations to obtain the naïve dimensional growth before any intervention. SARCULATOR nomogram was applied on data at Exam-0 and Exam-1. Correlations with overall, metastatic and local relapse-free survivals (OS, MFS and LFS), and with pre-treatment pathological features were performed. Results137 patients were included (median age: 65 years). Average naïve growth was +39.4% in LD and +503% in volume during an average Exam-0-to-Exam-1 interval of 130 days. The 10-year distant metastasis and OS predictions were different at Exam-0 and Exam-1 (P < 0.0001 for both). All the changes in radiological measurements significantly correlated with pre-treatment number of mitosis, grade and complex genomic (P-value range: <0.0001–0.0481). Multivariate Cox modeling identified the relative change in LD/month and absolute change in LD/month as independent predictors for OS and LFS, respectively (P = 0.0003 and 0.0001, respectively). ConclusionWhen available, the natural speed of growth on pre-treatment imaging should be evaluated to improve the estimation of pre-treatment histological grade and patients’ OS and LFS.

Preoperative prediction of gastrointestinal stromal tumors with high Ki-67 proliferation index based on CT features.

BackgroundTo determine whether preoperative computed tomography (CT) features can be used for the prediction of gastrointestinal stromal tumors (GISTs) with a high Ki-67 proliferation index (Ki-67 PI).MethodsA total of 198 patients with surgically and pathologically proven GISTs were retrospectively included. All GISTs were divided into a low Ki-67 PI group (<10%) and a high Ki-67 PI group (≥10%). All imaging features were blindly interpreted by two radiologists. Receiver operating characteristic (ROC) curve analyses were conducted to evaluate the predictive performance of the imaging features.ResultsImaging features were found to be significantly different between the low and the high Ki-67 PI groups (P<0.05). Wall thickness of necrosis showed the highest predictive ability, with an area under the curve (AUC) of 0.838 [95% confidence interval (CI): 0.627–0.957], followed by necrosis, necrosis degree, hyperenhancement of the overlying mucosa (HYOM), and long diameter (LD) (AUC >0.7, P<0.05). HYOM was the strongest predictive feature for the high Ki-67 PI GISTs group, with an odds ratio (OR) value of 30.037 (95% CI: 5.707–158.106).ConclusionsImaging features, including the presence of necrosis, high necrosis degree, thick wall of necrosis, and HYOM were significant predictive indicators for the high Ki-67 PI GISTs group.

Differentiation between small (< 4.5 cm) true subepithelial tumors and ectopic pancreas in the small bowel on computed tomography enterography.

To identify imaging features that can differentiate ectopic pancreas from true subepithelial tumors (SETs) in the small bowel using CT enterography and to assess whether radiologists' performance for the differentiation can be improved with the knowledge of significant CT findings. CT images of ectopic pancreas (n = 29) and pathologically proven SETs (n = 61) were retrospectively reviewed by two radiologists in consensus. CT items analyzed included lesion location, contour (round, ovoid, flat/conformed), growth pattern, margin, homogeneity, necrosis, feeding vessel, surface ulceration, and enhancement pattern. For quantitative analysis, Hounsfield unit, longer diameter (LD), and shorter diameter (SD) of the lesion were measured. Univariate and multivariate analyses were performed. Diagnostic performance for differentiating ectopic pancreas from SETs was independently evaluated by two other radiologists using a receiver operating characteristic analysis. Age < 63 years, female sex, flat/conformed appearance, homogeneous enhancement, the absence of feeding vessels and necrosis, and an LD/SD ratio > 1.5 were significant variables for differentiating ectopic pancreas from small bowel SETs (p < 0.05). In the multivariate analysis, flat/conformed appearance, the absence of feeding vessels, and female sex remained suggestive features for ectopic pancreas. Area under the curve values for differentiating between two disease entities increased by both independent reviewers with knowledge of these significant CT features. Ectopic pancreas in the small bowel can be effectively differentiated from small (< 4.5 cm) true SETs by a flat/conformed appearance and the absence of feeding vessels on CT enterography. In addition, radiologists' performance for differentiating ectopic pancreas from small bowel SETs was improved with the knowledge of these significant CT findings. • Ectopic pancreas in the small bowel can be differentiated from small (< 4.5 cm) subepithelial tumors on CT. • Differential CT findings of the ectopic pancreas are a flat or conformed appearance and the absence of a feeding vessel. • Radiologists' performance for differentiating ectopic pancreas from small bowel SETs can be improved with the knowledge of differential CT findings.

Evaluating the effect of Neoadjuvant chemotherapy for esophageal Cancer using the RECIST system with shorter-axis measurements: a retrospective multicenter study

BackgroundEvaluating the effect on primary lesions is important in determining treatment strategies for esophageal cancer. The Response Evaluation Criteria in Solid Tumors system, which employs the longest diameter for measuring tumors, is commonly used for evaluating treatment effects. However, the usefulness of these criteria in assessing primary esophageal tumors remains controversial. Thus, we evaluated this issue by measuring not only the longest diameter but also the shorter axis of the tumor.MethodsWe retrospectively reviewed data from 313 patients with esophageal cancer treated with neoadjuvant chemotherapy followed by esophagectomy at three major high-volume centers in Japan. All patients underwent contrast-enhanced computed tomography before and after chemotherapy. The longest and shortest tumor diameters were measured in each case. Treatment effects were adapted to the Response Evaluation Criteria in Solid Tumors system. Correlations between pathological and survival data were also analyzed.ResultsInter-observer discrepancies were examined for changes in the longest diameter and shorter axis of the tumor (the intraclass correlation coefficients were 0.550 and 0.624, respectively). The shorter axis was correlated with the pathological response in the multivariate analysis (p < 0.001). The shorter axis was significantly associated with overall survival and disease-free survival (both p < 0.001), whereas this association was not observed for the longest tumor diameter.ConclusionsThis multicenter study demonstrated that the Response Evaluation Criteria in Solid Tumors system is useful for predicting pathological response and survival by incorporating the shorter axis of the primary esophageal tumor.

Analysis of Primary Iris and Ciliary Body Cysts in Chinese Patients With Primary Angle Closure Disease.

Aim: To investigate the incidence and clinical features of primary iris and ciliary body cysts in Chinese primary angle closure disease (PACD). Patients were evaluated by measuring and analyzing the cysts with an ultrasound biomicroscope (UBM).Methods: The data of patients diagnosed with PACD were reviewed. Demographic data were collected, and the cyst number, size, location, and trabecular-iris angle (TIA) were measured, with the size including the longest diameter (LD) and its corresponding vertical diameter (CVD).Results: A total of 1,334 cases (2,317 eyes) were reviewed, and 409 cysts were found in 131 cases (168 eyes), with an average of 2.43 ± 3.14 cysts per eye. The ages of the patients with cysts ranged from 25 to 80 years, with an average age of 55.24 ± 12.22 years. The detection rate was 7.3%, and the majority of cysts were located in the iridociliary sulcus. Among the 131 patients, 94 had monocular cysts, while binocular cysts occurred in 37 patients. The locations of the cysts in both eyes were mainly in the inferior and temporal quadrants (42.5 and 34.0%, respectively). The cysts were mainly of medium size (49.9%), followed by small cysts (33.3%), large cysts (14.7%) and giant cysts (2.2%). The average LD was 0.68 ± 0.33 mm, and the average CVD was 0.45 ± 0.23 mm. There were no statistically significant differences in the TIA between the cyst area and unaffected area.Conclusions: The incidence of cysts is 7.3% in the PACD population. The cysts are mainly monocular, medium in size, and located in the iridociliary sulcus. Additionally, the cysts were located mainly in the inferior and temporal quadrants. These cysts have little effect on the anterior chamber angle.

Preliminary study on ultrasound-guided high-intensity focused ultrasound ablation for treatment of broad ligament uterine fibroids

Objective To investigate the feasibility, efficacy and safety of ultrasound-guided high-intensity focused ultrasound (HIFU) ablation for treating the broad ligament uterine fibroid (BLUF). Methods A total of 236 patients with symptomatic uterine fibroids were enrolled and treated with JC-200 extracorporeal ultrasound-guided HIFU under conscious sedation between January 2017 and December 2018. Of them, data of 12 patients with 13 broad ligament fibroids were retrospectively analyzed. The patients’ mean age was 38.6 ± 6.3 years. The focused ultrasound target was deployed and moved from the deeper layer to the superficial layer of BLUFs. All patients underwent contrast-enhanced MRI (CE-MRI) before, immediate post-operation, and six months after the HIFU ablation procedure. The fibroid size, non-perfusion volume (NPV) ratio, the reduction of fibroid volumes, adverse events, symptom changes, and abnormal MRI findings associated with the HIFU treatment were analyzed. Results Ultrasound-guided HIFU ablation in the twelve patients was technically successful with one session treatment. The mean longest diameter of BLUFs was 6.2 ± 2.3 cm. The mean NPV ratio of fibroids was 84.08%± 9.4%. After HIFU ablation, lower abdominal pain occurred in 7 cases, sacrococcygeal pain in 3 cases, and mild skin pain in 6 cases. There were no severe adverse events and complications associated with the treatment. At 6 months post-treatment follow-up, the mean fibroid volume decreased by 56.2%± 9.0% (p < 0.05), and the symptoms related to broad ligament fibroids were improved or disappeared Conclusions Ultrasound-guided high-intensity focused ultrasound ablation is feasible, effective, and safe for treating broad ligament fibroids.

Prognosis of patients with severe cerebral venous thrombosis treated with decompressive craniectomy

IntroductionDespite the highly favorable prognosis, mortality occurs in nearly 2% of patients with cerebral venous thrombosis (CVT), in which decompressive craniectomy (DC) may be the only way to save the patient's life. The aim of this report is to describe the risk factors, neuroimaging features, in-hospital complications and functional outcome of severe CVT in patients treated with DC. Materials and methodsConsecutive malignant CVT cases treated with DC from a retrospective third-level hospital database were analyzed. Demographic, clinical, and functional outcomes were analyzed. ResultsTwenty-six patients were included (20 female, age 35.4±12.1 years); 53.8% of the patients had acute CVT, with neurological focalization as the most common symptom in 92.3% of the patients. Superior sagittal sinus thromboses were found in 84.6% of cases. Bilateral lesions were present in 10 patients (38.5%). Imaging on admission showed a parenchymal lesion (venous infarction±hemorrhagic lesion)>6cm measured along the longest diameter in 25 patients (96.2%). Mean duration of clinical neurological deterioration was 3.5 days; eleven patients (42.3%) died during hospitalization. ConclusionIn patients with severe forms of CVT, we found higher mortality than previously reported. DC is an effective life-saving treatment with acceptable functional prognosis for survivors.

Abstract 1700: Immune effects of high intensity focused ultrasound ablation with checkpoint inhibitors in murine neuroblastoma

Abstract Background: Pediatric solid tumors have not shared in the success of immunotherapy, possibly due to mechanisms impeding an effective immune response. High intensity focused ultrasound (HIFU) ablation uses ultrasound energy to non-invasively and precisely destroy targeted tumor tissue and can cause local inflammatory responses. Our group previously showed a significant survival benefit with increased antitumor cytokine and cellular response treating refractory, murine neuroblastoma (N2a) with HIFU boiling histotripsy (BH) and αCTLA-4 + αPD-L1. We sought to reproduce these bioeffects using HIFU ablation with αCTLA-4 + αPD-L1. Methods: N2a tumors were established in the hindlegs of A/J mice and when tumors reached longest diameter of 12-15mm, mice were treated with 1) HIFU ablation alone (n =36), 2) HIFU ablation with αCTLA-4 + αPD-L1 (n = 35) or 3) no treatment (n = 14). Mice were treated with HIFU ablation (1.5MHz transducer, 35W acoustic power, 3 foci x 5 sec) under ultrasound imaging guidance. αCTLA-4 + αPD-L1 were injected on days 1, 4 and 7 after HIFU ablation. Survival endpoints were euthanasia due to poor clinical status or tumor size &amp;gt;20mm. ELISA (serum), and flow cytometry (tumors, draining and contralateral lymph nodes (DLN , CLN), and spleen) were performed at 24, 48 and 72 hour time points after HIFU ablation alone or with αCTLA-4 + αPD-L1. Results: HIFU ablation alone or with αCTLA-4 + αPD-L1 did not provide a significant survival benefit. Following HIFU ablation alone, there was significant downregulation of CD8α+CD11c+ cells in tumor and DLN but no other statistically significant changes in immune cell markers compared to control. After HIFU ablation and αCTLA-4 + αPD-L1, CD8α+Ki67+ increased in tumor and DLN, but higher expression of CD3+CD8+ was not observed. CD4+FoxP3- cells remained unchanged but CD4+FoxP3+ population increased in the tumor, DLN, CLN and spleen. Interestingly, PD-1 expression was upregulated on CD3+ and CD8α+ cells in tumor, DLN, CLN and spleen. IFN-Γ, CXCL-10 and TNF-α were unchanged after HIFU ablation alone but increased following the combination therapy. IL-10 and VEGF-A were not affected by either treatment and KC/GRO decreased steadily after HIFU ablation with αCTLA-4 + αPD-L1. Conclusion: Unlike BH with immunotherapy, HIFU ablation with immunotherapy did not improve survival in this N2a model. HIFU ablation and αCTLA-4 + αPD-L1 did not produce a profound immune response and favored a regulatory T cell response with protumor activity. This is in stark contrast to the immune response seen with BH and immunotherapy despite the same tumor model and experimental set up. It will be important to understand the role of PD-1 and other protumoral factors, to investigate the effect of other HIFU parameters on systemic immune antitumor response and to evaluate this approach in other murine cell line models for broader clinical applicability of this combination therapy. Citation Format: Caitlin Tydings, Avinash Eranki, Karun V. Sharma, AeRang Kim, Priya Srinivasan, Christopher Lazarski, Christopher Rossi. Immune effects of high intensity focused ultrasound ablation with checkpoint inhibitors in murine neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1700.

Ultrasound-guided microwave ablation for multiple benign breast lesions: A prospective study.

To provide medical evidence for the feasibility and clinical efficacy of microwave ablation (MWA) in the treatment of benign breast lesions, especially multiple benign breast lesions. We included patients with multiple benign breast lesions who were seen at our hospital during the period from June 2016 to December 2017. After signed informed consent had been obtained and core breast biopsy, all included patients who underwent MWA at 2450 MHz with 30 W power adjustment. Postoperative follow-up was performed for 1 year, at 3-month intervals. Ablation time, complications, volume-reduction ratio (VRR), and lesion residuals after ablation were analyzed. We ultimately included 1274 lesions from 164 cases in the study with a median follow-up time of 13.6months. For a single lesion, the median ablation time was 36 s. Pain, fat liquefaction, and skin scalding were the most common complications. The overall complete disappearance rate was 92.1% (1173/1274), with the highest complete disappearance rate observed among those patients with lesions <10 mm in diameter (942/968, 97.3%). For lesions that persisted at 12 months after MWA, the average the volume-reduction ratio (VRR) was 87.5%. For multiple benign lesions of the breast, especially lesions with the longest diameter <10 mm, ultrasound guided MWA is a minimally invasive, relatively quick therapeutic strategy associated with accuracy in treatment and few complications.

Phase I study of autolytic immunotherapy of metastatic neuroendocrine tumors using intralesional rose bengal disodium.

4115 Background: Metastatic neuroendocrine neoplasms (mNEN) originating in the gastrointestinal tract are frequently slow growing yet both symptom and disease control remain important. Treatment options include resection, systemic somatostatin analogues (SSA), and systemic peptide receptor radionuclide therapy (PRRT). Additional options are needed; we have explored intralesional (IL) rose bengal disodium (PV-10), an investigational autolytic immunotherapy that can yield immunogenic cell death and disease-specific functional adaptive immunity. Methods: This phase 1 study evaluated safety, tolerability and impact on symptoms and biochemical markers resulting from IL PV-10 administered percutaneously to hepatic lesions in patients (pts) with progressive mNEN not amenable to resection or other potentially curative therapy. Eligible lesion(s) were 1.0 - 3.9 cm in longest diameter with amount of PV-10 administered proportional to size. Cohort 1 (n = 6 pts) received PV-10 to a single lesion per treatment cycle; Cohort 2 (n = 6) could receive injection to multiple lesions per treatment cycle. Pts could receive further PV-10 ≥6 weeks after prior injection. The primary endpoint was safety. Secondary endpoints included objective response rate (ORR) assessed by contrast enhanced CT (RECIST 1.1) and 68Ga-DOTATATE PET, biochemical response (CgA) and patient-reported outcome (EORTC QLQ-C30 and GI.NET21 QOL instruments). Results: Twelve pts were enrolled, 50% male, median age 66 yrs (range 47-79). Primary sites: 7 small bowel, 2 pancreas, 1 caecal, 2 unknown; grade: Gd1 = 5, Gd2 = 7. All pts had received SSA and PRRT as part of previous therapy and all had symptomatic, progressive disease. Median CgA was 1585 (range 35-10370). One lesion was injected per cycle for all 12 pts; none were suitable for multiple injections. One pt received 4 sequential PV-10 treatment cycles, 3 received 2 cycles, and 8 received 1 cycle. Toxicity was consistent with experience in other hepatic malignancies: post-procedure pain was reported by most pts; grade 3 photosensitivity reaction occurred in 1 pt; and grade 1 elevation of hepatic enzymes attributed to PV-10 occurred in 2 pts, resolving by day 7. Additionally, carcinoid flare occurred in 1 pt. ORR of injected lesions was 42%; patient-level disease control was 84%. Estimated PFS was 9.2 months; median OS was 22.5 months. CgA remained stable in 10 pts and upregulation of NK and activated CD4+ T lymphocytes was observed post-injection. QOL data at months 1 and 3 showed stable or improved carcinoid symptoms and global health status in 9 pts. Conclusions: PV-10 elicited no safety concerns with encouraging evidence of both local and systemic disease and symptom control in a heavily pre-treated population. Multiple cycles were delivered safely in suitable patients. Adaptive immune upregulation is consistent with other solid tumors and supports potential systemic benefit. Clinical trial information: NCT02693067.

Multicenter phase I/II trial of encorafenib with and without binimetinib in combination with nivolumab and low-dose ipilimumab in metastatic BRAF-mutant melanoma.

TPS9596 Background: Targeted therapy (BRAF + MEK inhibitors) and immunotherapy (anti-PD1 + anti-CTLA4) have improved overall survival for metastatic or unresectable BRAFV600E/Kmutant melanoma. Whereas targeted therapy has a high response rate, immunotherapy may deliver longer term disease control for a larger number of patients. Despite these treatments, patients with high risk metastatic melanoma such as those with brain or liver metastases, elevated lactate dehydrogenase (LDH) and bulky disease have inferior treatment outcomes with current therapies. A BRAF+MEK+PDL1 regimen has recently emerged however the role for this treatment remains unclear. Several recent trials combining MEK inhibition and immunotherapy have failed possibly because MEK inhibition can compromise T cell activation. Meanwhile the addition of CTLA4 blockade to PD1 inhibition appears to disproportionately benefit patients with non-T cell-inflamed tumors and potentially high-risk disease. For patients with high risk BRAF-mutant metastatic melanoma, further investigation of BRAF/MEK targeted and PD-1/CTLA-4 directed immunotherapy combination strategies remains a priority. Methods: This is an open label, multi-site, Phase 1/2 study of encorafenib (Enco) +/- binimetinib (Bini) + nivolumab (Nivo) + ipilimumab (Ipi) for the treatment of patients with unresectable or metastatic BRAF-mutated melanoma in high-risk cohorts (NCT04655157). An initial regimen confirming Phase I approach will be pursued on two schedules concurrently, with patients accruing equally to each group. Group 1 will receive 3mg/kg Nivo, and 1 mg/kg Ipi and 300mg Enco (12 participants, triple therapy) and Group 2 will receive 3mg/kg Nivo and 1mg/kg Ipi and 450mg Enco and 45mg Bini, (12 participants, quadruple therapy). Dose limiting toxicity (DLT) will be evaluated weeks 1-6. A recommended Phase II regimen (RP2R) [either triple or quadruple therapy] will be carried forward into two high risk metastatic disease cohort expansions of 30 participants each. Cohort 1 will include patients with symptomatic brain metastases, while cohort 2 will include patients with elevated LDH as well as either liver metastases OR bulky visceral disease (sum of longest diameters &gt; 44mm). Patients meeting criteria for cohorts 1 and 2 will be placed in cohort 1. Patients with symptomatic brain metastases will be included with an ECOG up to 2 and on ≤ 4mg of dexamethasone or equivalent. Continuous Bayesian toxicity monitoring will be used throughout to monitor DLT. Pre and on-treatment tumor biopsies will assess changes in the tumor microenvironment while peripheral blood ctDNA and T cell Ki67% changes will assess early response and immune activation during triplet and quadruplet therapy. Clinical trial information: NCT04655157.

Tumor growth inhibition modeling of individual lesion dynamics and interorgan variability in HER2-negative breast cancer patients treated with docetaxel.

Information on individual lesion dynamics and organ location are often ignored in pharmacometric modeling analyses of tumor response. Typically, the sum of their longest diameters is utilized. Herein, a tumor growth inhibition model was developed for describing the individual lesion time‐course data from 183 patients with metastatic HER2‐negative breast cancer receiving docetaxel. The interindividual variability (IIV), interlesion variability (ILV), and interorgan variability of parameters describing the lesion time‐courses were evaluated. Additionally, a model describing the probability of new lesion appearance and a time‐to‐event model for overall survival (OS), were developed. Before treatment initiation, the lesions were largest in the soft tissues and smallest in the lungs, and associated with a significant IIV and ILV. The tumor growth rate was 2.6 times higher in the breasts and liver, compared with other metastatic sites. The docetaxel drug effect in the liver, breasts, and soft tissues was greater than or equal to 1.2 times higher compared with other organs. The time‐course of the largest lesion, the presence of at least 3 liver lesions, and the time since study enrollment, increased the probability of new lesion appearance. New lesion appearance, along with the time to growth and time‐course of the largest lesion at baseline, were identified as the best predictors of OS. This tumor modeling approach, incorporating individual lesion dynamics, provided a more complete understanding of heterogeneity in tumor growth and drug effect in different organs. Thus, there may be potential to tailor treatments based on lesion location, lesion size, and early lesion response to provide better clinical outcomes.

468 Is topical remetinostat gel an effective and safe treatment for basal cell carcinoma? Results of a phase 2, open label, single arm trial

Surgical excision remains the gold standard treatment for basal cell carcinoma (BCC). However, it is associated with potential morbidity, particularly for patients with multiple or recurrent tumors. To identify novel treatment option for BCC, we previously used molecular data from human BCCs to conduct a drug repositioning screen. Our results identified histone deacetylase (HDAC) inhibitors as the leading predicted therapeutic, strongly opposing the BCC gene-expression signature. We conducted a phase 2, open label, single arm and institution trial of the topical pan-HDAC inhibitor, remetinostat, as the first proof-of-principle study of this medication class for BCC. Participants with at least one BCC referred for excision at Stanford were recruited and instructed to apply 1% remetinostat gel three times daily for six weeks. Measurements of tumor diameter and photography were conducted at baseline and week 8, and remaining tumor was then excised for histological examination, with a subset also sent for immunohistochemistry (IHC). 25 participants with 33 BCCs were included in the per-protocol analysis. The objective response rate (the proportion of tumors achieving at least a 30% decrease in the longest diameter from baseline to week 8) was 69.7% (90% confidence interval 54-82.5%), and 54.8% of the tumors demonstrated complete resolution on histological examination. IHC staining supported the pharmacodynamic effect of the remetinostat, demonstrating increased acetylated histone H3 in the excised biopsies compared to baseline. No systemic adverse events were reported, and the medication was well tolerated. Remetinostat, a topical pan-HDAC inhibitor, is a safe and effective topical treatment for BCC, reducing disease burden in a clinically significant manner. Our results provide the first in-human validation of HDAC inhibitors as a potential therapeutic.

Percutaneous nephrolithotomy in children.

The high success rates of percutaneous nephrolithotomy (PCNL) in the clearance of large renal calculi has made it a primary mode of surgical management in adults. Similarly, in children too PCNL has been gaining ground and the indications for the same are on the rise. We retrospectively evaluated the safety and efficacy of this technique, in children below 18years of age. We retrospectively reviewed the inpatient, outpatient records, imaging films of all children with renal stones undergoing PCNL at our hospital. During the study period, 123 children underwent 129 PCNL at our centre for renal calculi. The mean age was 11.06years and 87 (70.73%) of the children were males. The size of the stones varied from 15 to 37 mms in the longest diameter. A complete staghorn was noted in six (4.65%) and a partial staghorn in nine (6.97%) children. Supine PCNL was performed in 21 (16.2%) children and remaining 102 (83.7%) children underwent PCNL in prone position. The mean drop in haemoglobin was 1.24 gm%. Stone clearance was achieved in 122 (94.5%) children. Post-operatively four (3.1%) children needed blood transfusions due to excessive bleeding. Refinements in percutaneous access techniques, miniaturization of instruments, and technologic advances in energy sources for lithotripsy have led to improvement of outcomes and have lowered the morbidity rates in children following PCNL. It is a safe and effective means of clearing large volumes of renal calculi with minimal morbidity.

Therapeutic outcome and related predictors of stereotactic body radiotherapy for small liver-confined HCC: a systematic review and meta-analysis of observational studies

Background and purposeStereotactic body radiotherapy (SBRT) is a promising ablative modality for hepatocellular carcinoma (HCC) especially for those with small-sized or early-stage tumors. This study aimed to synthesize available data to evaluate efficacy and explore related predictors of SBRT for small liver-confined HCC (≤ 3 lesions with longest diameter ≤ 6 cm).Materials and methodsA systematic search were performed of the PubMed and Cochrane Library databases. Primary endpoints were overall survival (OS) and local control (LC) of small HCC treated with SBRT, meanwhile, to evaluate clinical parameters associated with treatment outcome by two methods including subgroup comparisons and pooled HR meta-analysis. The secondary endpoint was treatment toxicity.ResultsAfter a comprehensive database review, 14 observational studies with 1238 HCC patients received SBRT were included. Pooled 1-year and 3-year OS rates were 93.0% (95% confidence interval [CI] 88.0–96.0%) and 72.0% (95% CI 62.0–79.0%), respectively. Pooled 1-year and 3-year LC rates were 96.0% (95% CI 91.0–98.0%) and 91.0% (95% CI 85.0–95.0%), respectively. Subgroup comparisons regarding Child–Pugh class (stratified by CP-A percentage 100%, 75–100%, 50–75%) showed there were statistically significant differences for both 1-year and 3-year OS rate (p < 0.01), while that regarding number of lesions, pretreatment situation, age (median/mean age of 65), macrovascular invasion, tumor size, and radiation dose (median BED10 of 100 Gy), there were no differences. In subgroup comparisons for LC rate, it showed number of lesions (1 lesion vs. 2–3 lesions) was significantly associated with 1-year LC rate (p = 0.04), though not associated with 3-year LC rate (p = 0.72). In subgroup comparisons categorized by other factors including pretreatment situation, age, CP-A percentage, macrovascular invasion, tumor size, and radiation dose, there were no significant differences for 1- or 3-year LC rate. To further explore the association between CP class and OS, the second method was applied by combining HR and 95% CIs. Results indicated CP-A was predictive of better OS (p = 0.001) with pooled HR 0.31 (95% CIs 0.11–0.88), which was consistent with subgroup comparison results. Concerning adverse effect of SBRT, pooled rates of grade ≥ 3 hepatic complications and RILD were 4.0% (95% CI 2.0–8.0%) and 14.7% (95% CI 7.4–24.7%), respectively.ConclusionThe study showed that SBRT was a potent local treatment for small liver-confined HCC conferring excellent OS and LC persisting up to 3 years, even though parts of included patients were pretreated or with macrovascular invasion. CP-A class was a significant predictor of optimal OS, while number of lesions might affect short term tumor control (1-year LC). Tumor size and radiation dose were not vital factors impacting treatment outcome for such small-sized HCC patients. Because of the low quality of observational studies and heterogeneous groups of patients treated with SBRT, further clinical trials should be prospectively investigated in large sample sizes.

Bilateral renal angiomyolipomas and subependymal giant cell astrocytoma associated with tuberous sclerosis complex: A case report and review of the literature

Tuberous sclerosis complex (TSC) is an autosomal-dominant multi system disorder. The genetic basis of the disorder is mutations in the TSC1 or TSC2 gene, which leads to over activation of the mammalian target of rapamycin (mTOR) protein complex and results in development of benign tumors in different body systems such as brain, skin, lungs and kidney. The mTOR inhibitors are presently the main treatment option for patients with TSC. We here report a 21-year female patient with large bilateral angiomyolipoma (AML) in both kidneys with longest diameter more than 12.3 cm and subependymal giant cell astrocytoma (SEGA). Treatment with everolimus (EVE) was initiated at a dose of 10.0 mg/day and continued during the following 3 years. Magnetic resonance imaging (MRI) was performed before treatment with everolimus was initiated, and consequently at 12 and 36 months for follow-up of the efficacy of the treatment. After 3 years, the total size of largest AML decreased by ~24.0% in the longest diameter. A reduction of the total size of SEGA was also observed. The most common adverse effect of treatment was stomatitis grades 3 to 4 and one febrile episode associated with skin rash that required a reduced dose of EVE. In conclusion, the everolimus treatment improved even such a large renal AML and the effect persisted during the long-term administration with a small number of adverse effects. A positive effect was observed on the brain tumor as well.

Multivariate Analysis of Solid Pulmonary Nodules Smaller than 1 cm in Distinguishing Lung Cancer from Intrapulmonary Lymph Nodes

背景与目的肺实性小结节的术前诊断及鉴别诊断十分困难。计算机断层扫描（computed tomography, CT）作为肺癌筛查的常用手段，被广泛应用于临床。本研究旨在对 < 1 cm的肺实性结节临床诊疗中肺恶性结节与肺内淋巴结患者的临床资料进行分析，为两者的鉴别提供参考。方法回顾性分析2017年6月-2020年6月行手术治疗的肺实性结节患者。共收集了145个结节（肺腺癌60个，肺类癌2个，恶性间皮瘤1个，肉瘤样癌1个，淋巴结81个）的患者临床资料，最终分为肺腺癌和肺内淋巴结两组，并对其临床资料进行了统计分析。根据单因素分析（χ2检验、t检验）结果筛选有统计学差异的变量，纳入Logistic回归多因素分析，确定预测变量并绘制受试者工作曲线（receiver operating characteristic, ROC）曲线，得到曲线下面积（area under the curve, AUC）值。结果Logistic回归分析显示结节最长径、Max CT值、分叶征和毛刺征是肺腺癌与肺内淋巴结鉴别的重要指标，风险比分别为106.645（95%CI: 3.828-2, 971.220, P < 0.01）、0.980（95%CI: 0.969-0.991, P < 0.01）、3.550（95%CI: 1.299-9.701, P=0.01）、3.618（95%CI: 1.288-10.163, P=0.02）。根据Logistic回归分析结果确定预测模型，绘制ROC曲线，计算曲线下面积AUC值=0.877（95%CI: 0.821-0.933, P < 0.01）。结论对于 < 1 cm的肺实性结节，在众多因素中，肺结节最长径、Max CT值、分叶征和毛刺征对鉴别肺恶性结节和肺内淋巴结更为重要。

Clinical outcomes of bulky parotid gland cancers: need for self-examination and screening program for early diagnosis of parotid tumors

BackgroundEarly detection and diagnosis of parotid gland cancer (PGC) are essential to improve clinical outcomes, because Tumor-Node-Metastasis stage at diagnosis is a very strong indicator of prognosis in PGC. Nevertheless, some patients still present with large parotid mass, maybe due to the unawareness or ignorance of their disease. In this study, we aimed to present the clinical outcomes of bulky PGC (defined by a 4 cm cutoff point for T3–4 versus T1–2 tumors), to emphasize the necessity of a self-examination tool for parotid gland tumor.MethodsWe retrospectively reviewed 60 consecutive cases with bulky (equal to and greater than 4 cm in the longest diameter, determined radiologically) malignant tumors arising from the parotid gland from 1995 to 2016. The clinical and pathological factors were analyzed to identify risk factors for poor outcomes using Cox proportional hazard models. In addition, we designed a self-examination tool for parotid gland tumors, similar to breast self-examination for breast cancer detection.ResultsPatients with bulky parotid cancer showed 48.9% 5-year and 24.5% 10-year overall survival rates and a 47.9% risk of high-grade malignancy. The common pathological diagnoses were carcinoma ex pleomorphic adenoma (18.3%), adenocarcinoma (16.7%), mucoepidermoid carcinoma (16.7%), salivary duct carcinoma (16.7%), and adenoid cystic carcinoma (11.7%). Survival analyses revealed that tumor size (hazard ratio, HR = 1.262 upon increase of 1 cm, 95% confidence interval, 95%CI 1.059–1.502), lymph node metastasis (HR = 2.999, 95%CI 1.048–8.583), and high tumor grade (HR = 4.148, 95%CI 1.215–14.154) were independent prognostic factors in multivariable analysis. Functional preservation of the facial nerve was possible only in less than half of patients.ConclusionIn bulky PGC, lymph node metastasis at diagnosis and high tumor grade indicated poor survival outcomes, and functional outcomes of the facial nerve were suboptimal. Thus, a public effort seems to be necessary to decrease these patients with bulky PGC, and to increase patients’ self-awareness of their disease. As a way of early detection, we proposed a parotid self-examination tool to detect parotid gland tumors at an early stage, which is similar to breast self-examination.