Preoperative Systemic Chemotherapy Research Articles

Abstract PO4-20-05: An open label phase III randomized trial to evaluate the efficacy of Post-chemotherapy Axillary Conservation Surgery in breast cancer (PACS)

Abstract Background- Axillary lymph nodes (ALN) status is the most important prognostic factor in breast cancer. Traditionally, a complete axillary lymph node dissection (ALND) has been standard of care for those patients who have a positive node pre-chemotherapy. However, lately axillary conservation is paving its way in the post-chemotherapy setting as well to avoid significant morbidity of ALND. Most sentinel node biopsy studies have failed to achieve the desired false negative rate(FNR). (Boughey JC et al, JAMA. 2013 Oct; Kuehn T et al, Lancet Oncol. 2013; Boileau JF et al, J Clin Oncol. 2015 Jan).We previously reported a low FNR of low axillary sampling (LAS) in the post-chemotherapy setting. (Parmar et al, JCO-GO, 2021) We are conducting a phase III, randomised controlled trial of LAS versus complete ALND in post-chemotherapy negative (ypN0) axilla. Aims and objectives- The primary objective is to assess the non-inferiority of LAS in patients who are rendered ypN0 by pre-operative chemotherapy with disease-free survival as primary end point. The secondary objectives are comparing the morbidity of ALND (lymphedema, paraesthesia, and shoulder dysfunction) in the LAS and ALND arms, and to evaluate the impact on overall survival, local, regional, and distant recurrence free survival and quality of life. Trial design- This is a prospective, open label, randomised, phase III trial where histologically proven, non-metastatic, cT1-4,N0-2 breast cancer patients who are rendered ycN0 after pre-operative systemic chemotherapy are being accrued. Patients with prechemo N3 disease, inflammatory breast cancer, recurrent disease, pregnancy associated breast cancer are being excluded from the study. The chemotherapy regimens and surgical assessment is as per standard institutional protocols. After obtaining informed consent, patients undergo LAS during surgery and lymph nodes(LN) are sent for frozen section analysis. If any LN is found to be involved, a complete ALND is carried out. If the staging procedure is negative, then patients are randomised into 2 groups- observation v/s complete ALND. Stratification factors are T stage, N stage, Hormone receptor status, Her2 receptor status and number of chemotherapy cycles taken. Morbidity assessment is done with- Constans shoulder score, arm volumetry, paraesthesia assessment, and a QOL questionnaire- Self-reported Breast cancer Lymphedema Symptom Experience Index (BCLSEI). A baseline assessment pre-surgery is followed by 6 monthly morbidity assessments and regular oncologically relevant follow-up up to 5 years. A two-sided log-rank test with an overall sample size of 2316 with a 10% dropout rate (1158 in ALND and 1158 in LAS group) achieves 80% power at a 0.05 significance level to detect a hazard ratio of 1.16 (upper limit of non-inferiority) when the proportion surviving in the control group is 0.71. An interim analysis will be carried out at 25% events and conditional power will be calculated. If the conditional power is below 20%, then the study will be discontinued for futility. The study has been approved by Institutional Ethics Committee (CTRI/2022/07/044461) Expected Study and Results- We started accrual in February 2023 and have screened 63 and randomized 45 patients until now. Ours is a first large randomised prospective study in the post-chemotherapy axillary management setting which will help us understand the efficacy of axillary conservation surgery in patients who are node negative post neoadjuvant chemotherapy. In future, lesser morbid procedures than LAS like targeted axillary dissection can be tested in the same trial. However, LAS as a technique of axillary conservation suits resource constraints and high volume setting such as ours. Citation Format: Shalaka Joshi, Jessicka Shah, Pallavi Daphale, Rohini Hawaldar, Anuradha Daptardar, Ayushi Sahay, Tanuja Shet, Palak Popat, Tabassum Wadasadawala, Nita Nair, Vani Parmar, Bipin Bandre, Shabina Siddique, Vaibhav Vanmali, Sudeep Gupta, Rajendra Badwe. An open label phase III randomized trial to evaluate the efficacy of Post-chemotherapy Axillary Conservation Surgery in breast cancer (PACS) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-20-05.

Proximal gastric cancer—time for organ-sparing approach?

IntroductionA steady increase in gastroesophageal junction and proximal gastric cancer (GC) incidence has been observed in the West. Given recent advances in neoadjuvant chemotherapy (NAC), we sought to characterize short- and long-term outcomes of patients with proximal GC who underwent total (TG) versus proximal gastrectomy (PG). MethodsPatients with stage II/III proximal GC who underwent curative intent treatment between 2009 and 2019 were identified using National Cancer Database (NCDB). Multivariable analysis was used to identify oncological outcomes following TG versus PG. ResultsAmong 7,616 patients with GC who underwent surgical resection, PG and TG were performed on 5,246 (68.8%) and 2,370 (31.2%) patients, respectively. Patients who underwent PG were more likely to receive NAC (TG: 52.3% vs. PG: 64.5%)(p<0.001). On pathologic analysis, patients who underwent TG were more likely to have pT4 tumors (TG: 11.7% vs. PG: 3.1%), metastatic lymph nodes (TG: 64.6% vs. PG: 60.4%), and >16 lymph nodes evaluated (TG: 64.1% vs. PG: 53.1%), yet a lower likelihood of negative resection margins (TG: 86.6% vs. PG: 90.0%)(all p<0.001). While gastrectomy procedure type did not impact long-term survival, receipt of NAC was associated with OS among patients who underwent TG (5-year OS, NAC: 43.5% vs. no NAC: 24.6%) and PG (5-year OS, NAC: 43.1% vs. no NAC: 26.7%)(both p<0.001). ConclusionsPG may be an alternative surgical approach to TG in well-selected patients with proximal GC after administration of preoperative systemic chemotherapy.

Is Systemic Chemotherapy Useful in Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Colorectal Peritoneal Metastases? A Propensity-Score Analysis.

Multimodal treatment of colorectal (CRC) peritoneal metastases (PM) includes systemic chemotherapy (SC) and surgical cytoreduction (CRS), eventually with hyperthermic intraperitoneal chemotherapy (HIPEC), in select patients. Considering lack of clear guidelines, this study was designed to analyze the role of chemotherapy and its timing in patients treated with CRS-HIPEC. Data from 13 Italian centers with PM expertise were collected by a collaborative group of the Italian Society of Surgical Oncology (SICO). Clinicopathological variables, SC use, and timing of administration were correlated with overall survival (OS), disease-free survival (DFS), and local (peritoneal) DFS (LDFS) after propensity-score (PS) weighting to reduce confounding factors. A total of 367 patients treated with CRS-HIPEC were included in the propensity-score weighting. Of the total patients, 19.9% did not receive chemotherapy within 6 months of surgery, 32.4% received chemotherapy before surgery (pregroup), 28.9% after (post), and 18.8% received both pre- and post-CRS-HIPEC treatment (peri). SC was preferentially administered to younger (p = 0.02) and node-positive (p = 0.010) patients. Preoperative SC is associated with increased rate of major complications (26.9 vs. 11.3%, p = 0.0009). After PS weighting, there were no differences in OS, DFS, or LDFS (p = 0.56, 0.50, and 0.17) between chemotherapy-treated and untreated patients. Considering SC timing, the post CRS-HIPEC group had a longer DFS and LDFS than the pre-group (median DFS 15.4 vs. 9.8 m, p = 0.003; median LDFS 26.3 vs. 15.8 m, p = 0.026). In patients with CRC-PM treated with CRS-HIPEC, systemic chemotherapy was not associated with overall survival benefit. The adjuvant schedule was related to prolonged disease-free intervals. Additional, randomized studies are required to clarify the role and timing of systemic chemotherapy in this patient subset.

Open Prospective Phase II Randomized Trial Studying Preoperative Systemic and Regional Chemotherapy with Gemcitabine and Platinum-Based Agents in Resectable Intrahepatic Cholangiocarcinoma

Введение. У четверти пациентов с резектабельной внутрипеченочной холангиокарциномой (ВПХК) развивается прогрессирование в течение полугода после операции, прогноз жизни таких больных сопоставим с прогнозом жизни при консервативной терапии. Наличие факторов негативного прогноза, в т. ч. нерадикально выполненная резекция, отрицательно влияют на отдаленные результаты. Положительная роль адъювантного подхода у пациентов с резектабельной холангиокарциномой показана лишь в одной проспективной работе III фазы (BILCAP). Предоперационная терапия, согласно ретроспективным данным, может улучшить отдаленные результаты. Цель. Улучшить результаты лечения больных резектабельной ВПХК за счет применения предоперационной химиотерапии. Материалы и методы. Представленный протокол клинического исследования инициирован в ФГБУ «НМИЦ онкологии им Н.Н. Блохина» Минздрава России и одобрен локальным этическим комитетом 22.12.2022 г. Помимо вышеуказанного учреждения, в исследовании приняли участие еще четыре центра. Клиническое исследование зарегистрировано на портале https://db.oncoproct.ru (неоадъювантная химиотерапия при ВПХК). Исследование является многоцентровым, проспективным, рандомизированным. Предполагается оценить безопасность и эффективность неоадъювантной химиотерапии у больных с резектабельной ВПХК в сравнении со стандартным лечением — резекцией печени без предоперационной терапии. Первичная конечная точка: планируется достигнуть 95 % частоты R0 резекций. Вторичные конечные точки: частота объективного ответа, выраженность патоморфологического ответа, отдаленные результаты, переносимость предоперационной химиотерапии, частота и степень пострезекционных осложнений после предоперационной химиотерапии, частота соблюдения условий протокола. Планируется включить 94 пациента с резектабельной ВПХК, которые будут рандомизированы 1:1. Часть пациентов получит три курса системной терапии по схеме гемцитабин/цисплатин. У другой части пациентов введение препаратов в первый день курса будет назначено регионарно, путем внутриартериальной химиоинфузии, на восьмой день курса введение системное. Группа сравнения — исторический контроль — пациенты с резектабельной, по данным обследования, ВПХК, которые были подвергнуты резекции без предоперационной терапии, частота R0 резекции в этой группе составила 81,3 %. Заключение. Основываясь на результатах исследования, протокол которого представлен, будет сделано заключение о безопасности и целесообразности предоперационной химиотерапии при резектабельной ВПХК с использованием гемцитабина и препаратов платины, в т. ч. с применением внутрипеченочной инфузии.

Diagnosis, workup, and risk stratification of upper tract urothelial carcinoma.

Upper tract urothelial carcinoma (UTUC) is a relatively rare disease that presents unique challenges to urologists from both a diagnostic and management standpoint. UTUC is a clinically heterogenous disease with a varied natural history, and given its location in the upper urinary tract, treatment has the potential to cause or worsen chronic kidney disease. Therefore, physicians caring for patients with UTUC must be facile with multiple diagnostic and therapeutic strategies in order to provide optimal patient care. We present an overview of the epidemiology, histology, risk factors, and contemporary approach to the diagnosis, laboratory evaluation, imaging, and risk stratification for patients with UTUC. Computerized tomographic urography, thorough endoscopic evaluation, and biopsy (endoscopically or percutaneously) remain the standard of care for the diagnosis and staging of patients with suspected UTUC. Preoperative nomograms are vital to select patients more optimally for preoperative systemic chemotherapy and facilitate clinical trial enrollment. A thorough understanding of the various diagnostic challenges, imaging/pathologic limitations, biomarkers, and risk stratification tools will allow us as a field to develop new modalities to improve our diagnostic capabilities and reduce the risk of under diagnosis and over treatment for our patients.

Comparison of the therapeutic efficacy between systemic chemotherapy with and without radiofrequency ablation for colorectal cancer liver metastases: A propensity score matching study.

To compare therapeutic efficacy between systemic chemotherapy (SC) alone and preoperative SC followed by radiofrequency ablation (SC+RFA) in patients with colorectal cancer liver metastases (CRLM). This study identified a cohort of patients with CRLM after treatment between 2010 and 2016. Patients who received SC+RFA were compared with SC patients by propensity score matching. Overall survival (OS) and intrahepatic progression-free survival (PFS) were compared using stratified log-rank test. The outcomes after SC and SC+RFA were also assessed in patient subgroups. This study identified 338 patients with CRLM who had underwent SC and had different response to chemotherapy, including non-progressive disease (non-PD) or progressive disease (PD). Of this cohort, 64 patients in SC+RFA group were matched by propensity score to 64 patients who received SC alone. Compared with SC cohort, the SC+RFA cohort yielded better OS (HR, 0.403; 95% CI, 0.271-0.601) and PFS (HR, 0.190; 95% CI, 0.113-0.320). The estimated OS rates at 1, 3 and 5 years were 93.8%, 51.6% and 15.6% for SC+RFA group and 81.3%, 26.6% and 10.9% for SC group (p＜0.001). The cumulative PFS rates at 1, 3, and 5 years were 43.8 %, 14.1% and 3.1% for the SC+RFA group and 1.6%, 0 and 0% for SC group (p＜0.0001). In subgroup analysis, compared with patients with PD response, patients with non-PD response could gain better PFS (HR, 0.207; 95% CI, 0.121-0.354) and OS (HR, 0.390; 95% CI, 0.246-0.617). RFA was associated with improved OS and intrahepatic PFS in CRLM patients with preoperative SC,especially in non-PD response subgroup after SC. The addition of RFA was advocated for CRLM patients with preoperative SC. This study will provide important reference and evidence to better perform the management of unresectable CRLM.

Survival of patients with colorectal liver metastases treated with and without preoperative chemotherapy: Nationwide propensity score-matched study

IntroductionRoutine treatment with preoperative systemic chemotherapy (CTx) in patients with colorectal liver metastases (CRLM) remains controversial due to lack of consistent evidence demonstrating associated survival benefits. This study aimed to determine the effect of preoperative CTx on overall survival (OS) compared to surgery alone and to assess hospital and oncological network variation in 5-year OS. MethodsThis was a population-based study of all patients who underwent liver resection for CRLM between 2014 and 2017 in the Netherlands. After 1:1 propensity score matching (PSM), OS was compared between patients treated with and without preoperative CTx. Hospital and oncological network variation in 5-year OS corrected for case-mix factors was calculated using an observed/expected ratio. ResultsOf 2820 patients included, 852 (30.2%) and 1968 (69.8%) patients were treated with preoperative CTx and surgery alone, respectively. After PSM, 537 patients remained in each group, median number of CRLM; 3 [IQR 2–4], median size of CRLM; 28 mm [IQR 18–44], synchronous CLRM (71.1%). Median follow-up was 80.8 months. Five-year OS rates after PSM for patients treated with and without preoperative chemotherapy were 40.2% versus 38.3% (log-rank P = 0.734). After stratification for low, medium, and high tumour burden based on the tumour burden score (TBS) OS was similar for preoperative chemotherapy vs. surgery alone (log-rank P = 0.486, P = 0.914, and P = 0.744, respectively). After correction for non-modifiable patient and tumour characteristics, no relevant hospital or oncological network variation in five-year OS was observed. ConclusionIn patients eligible for surgical resection, preoperative chemotherapy does not provide an overall survival benefit compared to surgery alone.

A Case of Pararectal Lymph Node Metastasis from Pelvic Peritoneal Dissemination in Which Curative Resection of Transverse Colon Cancer Resulted in Long-Term Survival after Preoperative Systemic Chemotherapy and Surgery

症例は75歳の男性で，72歳時に横行結腸癌に対して腹腔鏡補助下結腸左半切除術を施行し病理組織学的診断はpT2N1，tub2，ly1，v2，pStage IIIaであった．術後補助療法としてUFT/UZEL6コース施行後再発なく経過していたが術後2年11か月目のCTで骨盤内腹膜播種再発が診断された．TEGAFIRI+Bev療法12コース施行後stable diseaseであり切除の方針となった．手術所見では直腸前壁漿膜面に結節を認め，低位前方切除術を施行した．病理組織学的所見では直腸結節は横行結腸癌の腹膜転移として矛盾しなかった．No. 251リンパ節に2個の転移リンパ節を認め，腹膜播種結節からのリンパ行性転移と考えられた．術後補助療法としてXELOX 3コース施行し以降無治療経過観察しているが，術後9年無再発生存中である．腹膜播種結節からのリンパ節転移は非常にまれであり報告する．

ASO Author Reflections: Which is the Optimal Preoperative Systemic Chemotherapy Regimen for Patients with Peritoneal Metastases from Colorectal Cancer?

ASO Author Reflections: Which is the Optimal Preoperative Systemic Chemotherapy Regimen for Patients with Peritoneal Metastases from Colorectal Cancer?

Performance of Node-RADS Scoring System for a Standardized Assessment of Regional Lymph Nodes in Bladder Cancer Patients.

Current cross-sectional imaging modalities exhibit heterogenous diagnostic performances for the detection of a lymph node invasion (LNI) in bladder cancer (BCa) patients. Recently, the Node-RADS score was introduced to provide a standardized comprehensive evaluation of LNI, based on a five-item Likert scale accounting for both size and configuration criteria. In the current study, we hypothesized that the Node-RADS score accurately predicts the LNI and tested its diagnostic performance. We retrospectively reviewed BCa patients treated with radical cystectomy (RC) and bilateral extended pelvic lymph node dissection, from January 2019 to June 2022. Patients receiving preoperative systemic chemotherapy were excluded. A logistic regression analysis tested the correlation between the Node-RADS score and LNI both at patient and lymph-node level. The ROC curves and the AUC depicted the overall diagnostic performance. In addition, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for different cut-off values (>1, >2, >3, >4). Overall, data from 49 patients were collected. Node-RADS assigned on CT scans images, was found to independently predict the LNI after an adjusted multivariable regression analysis, both at the patient (OR 3.36, 95%CI 1.68-9.40, p = 0.004) and lymph node (OR 5.18, 95%CI 3.39-8.64, p < 0.001) levels. Node-RADS exhibited an AUC of 0.87 and 0.91 at the patient and lymph node levels, respectively. With increasing Node-RADS cut-off values, the specificity and PPV increased from 57.1 to 97.1% and from 48.3 to 83.3%, respectively. Conversely, the sensitivity and NPV decreased from 100 to 35.7% and from 100 to 79.1%, respectively. Similar trends were recorded at the lymph node level. Potentially, Node-RADS > 2 could be considered as the best cut-off value due to balanced values at both the patient (77.1 and 78.6%, respectively) and lymph node levels (82.4 and 93.4%, respectively). The current study lays the foundation for the introduction of Node-RADS for the regional lymph-node evaluation in BCa patients. Interestingly, the Node-RADS score exhibited a moderate-to-high overall accuracy for the identification of LNI, with the possibility of setting different cut-off values according to specific clinical scenarios. However, these results need to be validated on larger cohorts before drawing definitive conclusions.

Similar Survival Among All Subtypes of Mucinous Appendiceal Adenocarcinoma Except the Intermediate Subtype, Which Shows an Improved Survival.

Limited success in the management of mucinous appendiceal adenocarcinoma (MACA) has been reported. Cytoreductive surgery with perioperative intraperitoneal chemotherapy was used to treat a cohort of patients with peritoneal dissemination of MACA. The clinical and histopathologic variables were assessed for their impact on overall survival. The study analyzed 196 patients during a median follow-up period of 8 years. The patients had a median age was 46 years, a median survival of 12 years, and a mean survival of 12.4 years. Preoperative systemic chemotherapy and a high prior surgical score had a negative impact on prognosis. Survival was better for 37 patients (18.9%) with mucinous appendiceal adenocarcinoma-Intermediate (MACA-Int) histology than for 159 patients (81.1%) with MACA grade 1, 2, or 3, or signet ring cells (S) (p = 0.0004). Although MACA-1 and MACA-2 versus MACA-3 and MACA-S had a difference in survival of 63.9 versus 43.2 years at 5 years, with long-term follow-up evaluation, the differences in survival became insignificant (p = 0.5841). The histologic subtype of MACA-Int had a 10-year survival of 81.1%, which was markedly superior to that of MACA-1, -2, -3, or -S (32.7%). With long-term follow-up evaluation, MACA-1, -2, -3, and -S did not differ significantly in survival.

Association of Systemic Chemotherapy Approaches With Outcomes in Appendiceal Peritoneal Metastases

IntroductionMany patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for appendiceal adenocarcinoma peritoneal metastases (APM) undergo preoperative systemic chemotherapy. The primary aim of this study is to evaluate differences in oncologic outcomes among two popular chemotherapy approaches in patients with APM undergoing CRS-HIPEC. MethodsWe performed a multicenter retrospective review of patients who underwent CRS-HIPEC for APM due to high or intermediate grade disease between 2013 and 2019. Patients in the total neoadjuvant therapy group (TNT) received 12 cycles of preoperative chemotherapy. Patients in the “sandwich” chemotherapy group (SAND) received six cycles of preoperative chemotherapy with a maximum of six cycles of postoperative chemotherapy. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS) defined as months from date of first treatment or surgery, respectively. ResultsA total of 39 patients were included in this analysis, with 25 (64%) patients in the TNT group and 14 (36%) patients in the SAND group. Patients in the TNT group had a median OS of 62 mo, while median OS in the SAND group was 45 mo (P = 0.01). In addition, patients in the TNT group had significantly longer RFS compared to the SAND group (35 versus 12 mo, P = 0.03). In a multivariable analysis, TNT approach was independently associated with improved OS and RFS. ConclusionsIn this multicenter retrospective analysis, a TNT approach was associated with improved overall and recurrence-free survival compared to a sandwiched chemotherapy approach in patients undergoing CRS-HIPEC for high or intermediate grade APM.

Oncologic aspects of the decision-making process for surgical approach for colorectal liver metastases progressing during chemotherapy.

Colorectal cancer represents the third most diagnosed malignancy in the world. The liver is the main site of metastatic disease, affected in 30% of patients with newly diagnosed disease. Complete resection is considered the only potentially curative treatment for colorectal liver metastasis (CRLM), with a 5-year survival rate ranging from 35% to 58%. However, up to 80% of patients have initially unresectable disease, due to extrahepatic disease or bilobar multiple liver nodules. The availability of increasingly effective systemic chemotherapy has contributed to converting patients with initially unresectable liver metastases to resectable disease, improving long-term outcomes, and accessing tumor biology. In recent years, response to preoperative systemic chemotherapy before liver resection has been established as a major prognostic factor. Some studies have demonstrated that patients with regression of hepatic metastases while on chemotherapy have improved outcomes when compared to patients with stabilization or progression of the disease. Even if disease progression during chemotherapy represents an independent negative prognostic factor, some patients may still benefit from surgery, given the role of this modality as the main treatment with curative intent for patients with CRLM. In selected cases, based on size, the number of lesions, and tumor markers, surgery may be offered despite the less favorable prognosis and as an option for non-chemo responders.

Preoperative systemic chemotherapy does not benefit for appendiceal pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is a clinically malignant tumour syndrome mainly derived from mucin-producing appendiceal tumours. This study aimed to explore the effect of preoperative systemic chemotherapy (PSC) before cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) on the safety and postoperative survival in patients with appendiceal PMP. We performed a retrospective analysis including consecutive patients with PMP undergoing primary surgery between January, 2008 and December, 2019 in Aerospace Center Hospital. The clinical data and postoperative survival were compared between PSC group and non-PSC group. Seven hundred and fifty patients were included in the study. Significant differences were found between PSC group and non-PSC group on clinicopathological data and perioperative outcomes and the independent risk factor of serious complications was blood loss >1000 mL (P=0.026). Shorter median overall survival (OS) was found (42 months, 95% CI 31.9-52.1) in PSC group than that (67 months 95% CI 44.5-89.5) in non-PSC group. In the stratified study with PCI < 20, CC 0/1 and low-grade pathological subtype, the OS from non-PSC group was significantly better than that in PSC group (log rank P-values are <0.001, 0.006 and <0.001, respectively). Multivariate survival analysis showed that CC 0/1, HIPEC, PCI < 20 and low-grade pathological subtype were the independent prognostic factors for better OS. PSC does not increase the risk of major perioperative complications in patients with appendiceal PMP, but it also does not bring postoperative survival benefits to patients either.

Neoadjuvant transcatheter arterial chemoembolization and systemic chemotherapy for the treatment of undifferentiated embryonal sarcoma of the liver in children.

BACKGROUNDUndifferentiated embryonal sarcoma of the liver (UESL) is a rare and aggressive mesenchymal tumor in children. Herein, we describe our experience in neoadjuvant therapy (NAT) and subsequent surgery for the treatment of UESL in children.AIMTo evaluate the efficacy of NAT and explore a new choice for successful operation of UESL in children.METHODSWe retrospectively analyzed six patients newly diagnosed with unresectable UESL who received NAT and then surgery at our center between January 2004 and December 2019. The tumor was considered unresectable if it involved a large part of both lobes of the liver or had invaded the main hepatic vessels or inferior vena cava. The NAT included preoperative transcatheter arterial chemoembolization (TACE) and systemic chemotherapy. The patients were 4 boys and 2 girls with a mean age of 7 years. The longest tumor at presentation ranged from 8.6 to 14.8 cm (mean, 12 cm). Extrahepatic metastases were present in 2 cases. Preoperative systemic chemotherapy was administered 3 wk after TACE. Tumor resection was performed 3 wk after one or two cycles of NAT. The patients received systemic chemotherapy after surgery.RESULTSAll patients successfully underwent NAT and complete resection. The tumor volumes decreased by 18.2%–68.7%, with a mean decrease of 36% after 1 cycle of NAT (t = 3.524, P = 0.017). According to the Response Evaluation Criteria In Solid Tumors criteria, 4 patients had a partial response and underwent surgery, while 2 had stable disease and received another cycle of NAT before surgery. Massive tumor necrosis was seen on pathological examination of the surgical specimen: > 90% necrosis in two, > 50% necrosis in three, and 25% necrosis in 1, with an average of 71.8%. Post-NAT complications included fever, nausea and vomiting, and mild bone marrow suppression. Elevated alanine transaminase levels occurred in all patients, which returned to normal within 7–10 d after treatment. No cardiac or renal toxicity, severe hepatic dysfunction, bleeding and non-target embolization were observed in the patients. The median follow-up period was 8 years with an overall survival of 100%.CONCLUSIONNAT effectively reduced tumor volume, cleared the tumor margin, and caused massive tumor necrosis. This may be a promising choice for successful surgery of UESL in children.

Systemic metastases from low-grade and high-grade pseudomyxoma peritonei: Treatments and outcomes

BackgroundThe metastasizing potential of pseudomyxoma peritonei (PMP) is largely unknown. We assessed incidence, impact on prognosis, treatments, and outcomes of systemic metastases after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). MethodsA prospective database of 327 patients undergoing CRS/HIPEC for PMP of appendiceal origin was reviewed. PMP was graded according to the Peritoneal Surface Oncology Group International (PSOGI) classification. Haematogenous metastases, and non-regional lymph-node involvement were considered as systemic metastases. ResultsAfter a median follow-up of 74.8 months (95% confidence interval [CI] = 68.0–94.8), systemic metastases occurred in 21 patients. Eleven patients were affected by low-grade PMP, and ten by high-grade PMP. Metastatic disease involved the lung (n = 12), bone (n = 1), liver (n = 4), distant nodes (n = 3), both lung and distant nodes (n = 1). Systemic metastases independently correlated with PSOGI histological subtypes (P = 0.001), and incomplete cytoreduction (P = 0.026). Median OS was 139.0 months (95%CI = 56.6–161.9) for patients who experienced systemic metastases, and 213.8 months (95%CI = 148.7-not reached) for those who did not (P = 0.159). Eight of eleven patients who had curative-intent surgery are presently alive at a median of 52.5 months (range 2.0–112.7). Seven are disease-free at a median of 27.4 months (range 2.0–110.4). At multivariate analysis, PSOGI histological subtypes (P = 0.001), completeness of cytoreduction (P = 0.001), and preoperative systemic chemotherapy (P = 0.020) correlated with poorer survival. Systemic metastases did not (P = 0.861). ConclusionsAfter CRS/HIPEC, systemic metastases occur in a small but clinically relevant number of patients, and the risk increases with incomplete cytoreduction and aggressive histology. In selected patients, surgical resection of metastatic disease can result in long survival.

Short-course radiotherapy and chemotherapy for conversion surgery in patients with unresectable metastatic rectal cancer: a preliminary case series study.

Curative treatment is challenging in patients with locally advanced rectal cancer and unresectable metastases. The aim of this study was to evaluate the clinical outcomes of short-course radiotherapy (RT) followed by systemic chemotherapy for patients with rectal cancer with mesorectal fascia (MRF) involvement and unresectable distant metastases. The study included consecutive patients diagnosed as having metastatic mid-to-low rectal cancer treated with short-course RT followed by systemic chemotherapy for conversion radical or palliative surgery between 2014 and 2019 at Gil Medical Center. The patients had primary rectal tumors involving the MRF and unresectable distant metastases. The treatment strategies were determined in a multidisciplinary team discussion. Seven patients (five men and two women) underwent short-course RT (5×5 Gy) and preoperative systemic chemotherapy. The median age was 68 years (range, 46-84 years), and the median distance from the anal verge to the primary tumor was 6.0 cm (range, 2.0-9.0 cm). During the median follow-up period of 29.4 months, three patients underwent conversion radical surgery with R0 resection, two underwent palliative surgery, and two could not undergo surgery. No postoperative major morbidity or mortality occurred. The patients who underwent conversion complete radical surgery showed good long-term survival outcomes, with an overall survival time of 29.4-48.8 months and progression-free survival time of 14.7-41.1 months. Short-course RT followed by systemic chemotherapy could provide patients with unresectable stage IV rectal cancer a chance to undergo to conversion radical surgery with good long-term survival outcomes.

Current practice patterns of society of urologic oncology members in performing inguinal lymph node staging/therapy for penile cancer: A survey study

ObjectivesInguinal lymph node (ILN) staging and therapeutic procedures are important for the diagnosis and management of suspected Inguinal lymph node metastasis in the setting of penile cancer. Morbidity associated with inguinal lymph node dissection (ILND) and the lack of standardization in its perioperative management are both significant. In this study, we aimed to define current management approaches and potential opportunities for improving outcomes. Methods and materialsA questionnaire was developed with 16 questions regarding pre, peri, and postoperative management of patients undergoing ILND. The questionnaire was approved by the Society of Urologic Oncology (SUO) Questionnaire Committee, which facilitated its dissemination through an initial email and a follow-up reminder to 1,003 members. The study was conducted from July to August, 2020. ResultsOf the 1,003 SUO members invited to participate, 93 responded (9.3% response rate); 49% performed 1 to 2 ILNDs annually, and 60% chose open ILND for high-risk primary cancer cN0. For suspicious lymph nodes > 2 cm, 69% preferred ILND, 86% preoperative systemic neoadjuvant chemotherapy, followed by surgery for bulky inguinal metastasis, and 84% used perioperative antibiotics (ABX), 53% of whom discontinued ABX 24 hours after surgery. Prophylactic anticoagulation was used by 78% of respondents, and 60% stopped it after ambulation. Specific ligation of lymphatics (versus none) was used by 82% of respondents, 55% obtained frozen sections, and 94% used inguinal drains. A saphenous sparing technique was used by 75% of respondents. An incisional wound vacuum device was used by 17% of respondents. Compression stockings and/or referral to a lymphedema specialist were used to manage postoperative lymphedema by 61% of respondents. ConclusionsResponses to a penile lymphadenectomy survey were relatively low and were primarily from the academic surgeon subset of the SUO. Significant consensus ( ≥ 70%) was noted for neoadjuvant chemotherapy for bulky nodal metastasis prior to surgery, perioperative antibiotic use, ligation of lymphatics, drain placement, and saphenous sparing dissection techniques. Other evidenced-based strategies that could decrease morbidity were rarely used, including dynamic sentinel node biopsy, incisional wound vacuums, and lymphedema prevention. Prospective trials are needed to validate and resolve existing treatment paradigms and to optimize perioperative pathways to reduce complications in penile cancer management.

Clinical impact of the biology of synchronous axillary lymph node metastases in primary breast cancer on preoperative treatment strategy.

The purpose of this study was to assess the utility of determining the biological features of synchronous axillary lymph node (syLN) metastasis of breast cancer in evaluating the efficacy of preoperative systemic chemotherapy (PST). The retrospective subjects initially comprised 59 patients (T1c-4 N1-3 M0) diagnosed with syLN metastasis via core needle biopsy who received PST. The hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status in each patient was assessed in primary breast tumor (pBT) and syLNs using immunohistochemistry, and the patients were classified into HR(+), HER2(+), and triple negative breast cancer (TN) subtypes. Subtype shift (SS) of pBT in syLNs was observed in 28% cases for HR(+), in 6% cases for the HER2(+), and in 16% cases for the TN. The pCR rate of the pBT and syLNs types were 45% and 36% in the HR(+), 45% and 39% in the TN, and 94% and 100% in the HER2(+), respectively. In SS cases, the pCR rate was significantly higher in 75% cases compared with 33% of the no-SS cases. A SS in syLNs was more frequent in HR(+) than in other types.

The Role of Hyperthermic Intraperitoneal Chemotherapy in Pseudomyxoma Peritonei After Cytoreductive Surgery

Studies on the prognostic role of hyperthermic intraperitoneal chemotherapy (HIPEC) in pseudomyxoma peritonei (PMP) are currently not available. To evaluate outcomes after cytoreductive surgery (CRS) and HIPEC compared with CRS alone in patients with PMP. This cohort study analyzed data from the Peritoneal Surface Oncology Group International (PSOGI) registry, including 1924 patients with histologically confirmed PMP due to an appendiceal mucinous neoplasm. Eligible patients were treated with CRS with or without HIPEC from February 1, 1993, to December 31, 2017, and had complete information on the main prognostic factors and intraperitoneal treatments. Inverse probability treatment weights based on the propensity score for HIPEC treatment containing the main prognostic factors were applied to all models to balance comparisons between the CRS-HIPEC vs CRS-alone groups in the entire series and in the following subsets: optimal cytoreduction, suboptimal cytoreduction, high- and low-grade histologic findings, and different HIPEC drug regimens. Data were analyzed from March 1 to June 1, 2018. HIPEC including oxaliplatin plus combined fluorouracil-leucovorin, cisplatin plus mitomycin, mitomycin, and other oxaliplatin-based regimens. Overall survival, severe morbidity (determined using the National Cancer Institute Common Terminology for Adverse Events, version 3.0), return to operating room, and 30- and 90-day mortality. Differences in overall survival were compared using weighted Kaplan-Meier curves, log-rank tests, and Cox proportional hazards multivariable models. A sensitivity analysis was based on the E-value from the results of the main Cox proportional hazards model. Differences in surgical outcomes were compared using weighted multivariable logistic models. Of the 1924 patients included in the analysis (997 [51.8%] men; median age, 56 [interquartile range extremes (IQRE), 45-65] years), 376 were in the CRS-alone group and 1548 in the CRS-HIPEC group. Patients with CRS alone were older (median age, 60 [IQRE, 48-70] vs 54 [IQRE, 44-63] years), had less lymph node involvement (14 [3.7%] vs 119 [7.7%]), received more preoperative systemic chemotherapy (198 [52.7%] vs 529 [34.2%]), and had higher proportions of high-grade disease (179 [47.6%] vs 492 [31.8%]) and suboptimal cytoreduction residual disease (grade 3, 175 [46.5%] vs 117 [7.6%]). HIPEC was not associated with a higher risk of worse surgical outcomes except with mitomycin, with higher odds of morbidity (1.99; 95% CI, 1.25-3.19; P = .004). HIPEC was associated with a significantly better overall survival in all subsets (adjusted hazard ratios [HRs], 0.60-0.68, with 95% CIs not crossing 1.00). The weighted 5-year overall survival was 57.8% (95% CI, 50.8%-65.7%) vs 46.2% (95% CI, 40.3%-52.8%) for CRS-HIPEC and CRS alone, respectively (weighted HR, 0.65; 95% CI, 0.50-0.83; P < .001; E-value, 2.03). Such prognostic advantage was associated with oxaliplatin plus fluorouracil-leucovorin (HR, 0.42; 95% CI, 0.19-0.93; P = .03) and cisplatin plus mitomycin (HR, 0.57; 95% CI, 0.42-0.78; P = .001) schedules. In this cohort study, HIPEC was associated with better overall survival when performed after CRS in PMP, generally without adverse effects on surgical outcomes.