Only Site Of Metastasis Research Articles

Abstract PO5-05-05: Clinical outcomes of CDK4/6 inhibitors in patients with bone only metastatic breast cancer

Abstract Background: CDK4/6 inhibitors (CDK 4/6i) have significantly advanced the treatment of hormone receptor-positive (HR+) metastatic breast cancer in the last decade. Several clinical trials including PALOMA, MONALEESA, and MONARCH have shown improved progression-free survival (PFS) rates when CDK4/6i were combined with endocrine therapy (ET). These results led to recommending their use in combination with ET as the first line of therapy in the metastatic settings. Bone metastasis is the most common site of disease in patients with HR+ metastatic breast cancer, about 40% of whom have bone as the only site of metastasis (bone-only disease [BoD]). While previous studies have shown that BoD can have a unique clinical course and a more favorable prognosis compared to non-BoD metastasis, most of the aforementioned CDK 4/6i clinical trials have not shown significant improvements in PFS in BoD subset of patients. Here we aimed to investigate the survival outcomes of BoD patients at a single institution center and evaluate CDK 4/6i activity in preclinical models of bone metastasis in breast cancer. Patients and methods: Patients with HR+, HER2-negative metastatic breast cancer from a retrospective CDK4/6i study at Washington University School of Medicine were included in this analysis. We selected all the patients who received CDK4/6i in the first- or second-line settings from June 2014 to March 2020. Outcomes were collected through June 10, 2023. The Kaplan-Meier method with log rank test and multivariable cox model were used for survival analysis. Results: 114 female patients (n=75 first line, n=39 second line, n=20 African American, n=94 Caucasian) were included in this study. All patients received Palbociclib as the first exposure to CDK4/6 inhibitor in combination with ET for at least two months. Median age was 60 years (range, 28-87) and forty-seven patients (41%) were in the BoD group. Survival outcomes for BoD group were compared to the rest of patients who had either bone and visceral or visceral only metastatic lesions (BV group). Our results demonstrated a significantly reduced median PFS in BoD group compared to BV group (13.1 months [95%CI:8-18.2] vs 19.6 months [95%CI:6.8-32.4], p=0.01) respectively. There was no significant difference in overall survival between BoD and BV groups (36.6 months [95%CI:32.2-41] vs 41.7 months [95%CI 36.1-47.2] p=0.74) respectively. In multivariate analysis regarding the associated risk factors with PFS, after adjusting for age and race, BoD had a HR of 1.62 (95%CI:1.04-2.54) for PFS. Among the 75 patients who received CDK4/6i as their first line of therapy, BoD (n=32 patients [42.7%]) also showed an inferior (p=0.05) median PFS (20 months [95%CI 12.9-27]) compared to BV group (n=43 patients [57.3%], median PFS=28.4 months [95%CI: 16.3-40.4]). To investigate potential treatment resistance mechanisms in bone metastases, we used the triple negative 4T1 and the ER+ luminal B PyMT Bo1 breast tumor cell line derived mammary gland models in immunocompetent mice. Single agent CDK4/6i, ribociclib, decreased primary mammary gland tumor burden. This effect was abrogated when CD8+ T-cells were depleted. In the bone colonization model using these cell lines, ribociclib had little effect on bone tumor burden. Arg1+ immune suppressive macrophages were significantly decreased in the primary mammary tumor but not in the bone tumor after ribociclib administration, suggesting a relative treatment resistance and immune suppression in the bone tumor microenvironment compared to the primary mammary gland. Conclusion: CDK4/6i play a significant role in the treatment of patients with HR+ metastatic breast cancer. Our single institution, retrospective study and preclinical data suggests that CDK4/6i may not be as effective for the treatment of tumors residing in the bone microenvironment, warranting future studies to understand the mechanisms of CDK4/6 inhibitors action in bone versus visceral metastases. Citation Format: Mahta Mardani, Suleyman Noordeen, Katherine Clifton, Cynthia Ma, Jingqin Luo, Jing Xi, Nusayba Bagegni, Foluso Ademuyiwa, Rama Suresh, Ashley Frith, Andrew Davis, Ron Bose, Lindsay Peterson, Shana Thomas, Yu Tao, Takayuki Kobayashi, Jingyu Xiang, Yalin Xu, Xinming Su, Katherine Weilbaecher. Clinical outcomes of CDK4/6 inhibitors in patients with bone only metastatic breast cancer [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 PO5-05-05.

Abstract LB344: A novel approach to limit off-tumor toxicity of CAR-T cells targeting solid cancers

Abstract T cells genetically engineered to express a chimeric antigen receptor (CAR) specific for the molecule CD19 have achieved significant gains in the treatment of chemotherapy-resistant leukemia and lymphoma. Despite evidence of long-lived cures in patients with metastatic solid cancer after receiving tumor-specific T cells, no CAR-T cell treatment is currently approved for use against any solid cancer. A large majority of solid cancers express one of many tumor-associated antigens (TAAs) that are vulnerable to CAR T cell recognition. However, in nearly all cases those same TAAs are present in healthy tissues. Since CAR T cells cannot differentiate between cancer and normal cells, CAR T cell recognition of TAAs on healthy tissues provokes dose-limiting ‘on-target off-tumor’ toxicities at sites of endogenous expression (lung, intestine). Thus, there remains a pressing need to develop strategies to mitigate off-tumor toxicity of CAR T cells. To this end, we develop two immunocompetent models of CAR T cell transfer targeting TAAs abundant in metastatic colorectal cancer and pancreatic cancer. TAA-specific CAR T cells affected tumor shrinkage along with infiltrating and damaging sites of endogenous expression (primarily lung, pancreas, & colon). In both of our models, off-tumor toxicities were antigen-dependent and resulted in tissue damage, systemic inflammation, and host death that was titratable to CAR-T cell dose. TAA-specific CAR T cells infiltrated sites of endogenous expression such as the intestine, pancreas, and lungs. Notably, the respiratory system was the site of greatest pathology in both of our models, with massive CAR T cell accumulation and tissue destruction that resulted in systemic wasting and rapid weight loss. Remarkably, we found that the presence of an antigen-bearing tumor in the liver, but not other sites, greatly exacerbated CAR-T cell pulmonary infiltration, tissue destruction, and host mortality.The liver is the most common site of metastasis in patients with colorectal and pancreatic adenocarcinoma and the only site of metastasis in one-third of colorectal cancers. Our models indicated that TAA-specific CAR-T cells given for the treatment of liver metastasis result in dose-limiting pulmonary toxicity due to the presence of the TAA in the healthy lung. To address this translational barrier, we designed and validated a multiparameter genetic reprogramming targeting T cell trafficking and tissue residency introduced with the CAR to imbue CAR-T cells with liver tropism. In multiple models, CAR T cells programmed with liver-specific tropism augmented CAR T cell liver trafficking, decreased lung infiltration and toxicity, and effectively treated TAA+ liver metastasis. We aim to initiate a pilot clinical trial using tissue resident-programmed CAR T cells to treat colorectal liver metastasis. Citation Format: Alex Bartlett, Matthew Mcwhorter, Camille Collier, Chelsea Jenkins, Robert Eil. A novel approach to limit off-tumor toxicity of CAR-T cells targeting solid cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB344.

Mesorectal nodal metastasis with seminal vesicle invasion in biochemically recurrent prostate cancer.

To determine the prevalence and predictors of mesorectal lymph node (MLN) metastases on prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) in patients with biochemically recurrent prostate cancer (PCa) following radical therapy. This was a cross-sectional analysis of all PCa patients with biochemical failure following radical prostatectomy or radiotherapy who underwent an 18 F-DCFPyL-PSMA-PET/CT at the Princess Margaret Cancer Centre between December 2018 and February 2021. Lesions with PSMA scores ≥2 were considered positive for PCa involvement (PROMISE classification). Predictors of MLN metastasis were evaluated using univariable and multivariable logistic regression analyses. Our cohort consisted of 686 patients. The primary treatment method was radical prostatectomy and radiotherapy in 528 (77.0%) and 158 patients (23.0%), respectively. The median serum PSA level was 1.15 ng/mL. Overall, 384 patients (56.0%) had a positive scan. Seventy-eight patients (11.3%) had MLN metastasis, with 48/78 (61.5%) having MLN involvement as the only site of metastasis. On multivariable analysis, presence of pT3b disease (odds ratio 4.31, 95% confidence interval 1.44-14.2; P = 0.011) was significantly associated with increased odds of MLN metastasis, whereas surgical factors (radical prostatectomy vs radiotherapy; performance/extent of pelvic nodal dissection), surgical margin positivity, and Gleason Grade were not. In this study, 11.3% of PCa patients with biochemical failure had MLN metastasis on 18 F-DCFPyL-PET/CT. pT3b disease was associated with 4.31-fold significantly increased odds of MLN metastasis. These findings suggest alternate drainage routes for PCa cells, either via alternate lymphatic drainage from the seminal vesicles themselves or secondary to direct extension from posteriorly located tumours invading the seminal vesicles.

Vascular access for isolated hepatic perfusion in liver metastases. Place of artificial circulation. Literature review

The use of an artificial circulation and endovascular technologies in the treatment of liver metastases of uveal melanoma is a highly relevant area. Uveal melanoma is a rare cancer from the uveal tract of the eye. The liver is the most common site of metastasis and is affected in 70-90% of cases, being the only site of metastasis in about 50% of cases. Survival ranges from two to three months. This literature review describes the following methods of treatment of liver metastases of uveal melanoma using a heart-lung machine: arterial (arterio-caval), portal (porto-caval), arterio-porto-caval, retrograde arterio-portal. Special attention is paid to the endovascular method of treatment.Literature sources were searched in the following electronic libraries: elibrary.ru, pubmed.ncbi.nlm.nih.gov, researchgate.net.

Metastatic rhabdomyosarcoma with exclusive distant lymph node involvement: A European Pediatric Soft tissue sarcoma Study Group (EpSSG) report.

The prognosis of patients with metastatic rhabdomyosarcoma (RMS) is not uniformly poor. Tumors with nodal involvement beyond the first lymph node station are currently considered to have distant metastases. The aim of this study is to evaluate the characteristics and outcome of RMS patients with distal nodal involvement as the only site of metastasis. This study included all patients with a diagnosis of RMS and distant nodal involvement as the only metastatic site, enrolled in the European Pediatric Soft tissue sarcoma Study Group (EpSSG) protocols. Treatment comprised chemotherapy, surgery, and/or radiotherapy. The main outcome measures were event-free survival (EFS) and overall survival (OS). A total of 22 patients (median age 7.1years, range 1.4-16.7) fit the inclusion criteria. The extremities were the most common primary tumor site (59%). Twenty-one patients had regional and distant nodal involvement, 12 were PAX3/7-FOXO1 positive. Twenty patients had radiotherapy including 16 to the nodal metastatic area. After a median follow-up of 53.9months (range 22.8-110.5), 15 patients remain in complete remission, seven had progressive disease or relapse, and six of them died. The 3-year EFS and OS were 67.1% (95% confidence interval [CI]: 42.9-82.9) and 71.9% (95% CI: 47.7-86.3), respectively. Patients with fusion-negative tumors had better outcomes than those with fusion-positive tumors (3-year EFS 100% vs. 46.6%; p=.04). In our experience, patients with RMS and distant lymph node involvement as the only site of metastasis present an outcome superior than other metastatic patients and comparable to patients with locoregional nodal involvement. In particular, excellent outcomes were seen in the limited number of patients with fusion-negative tumors.

Tumores neuroendocrinos pulmonares, cáncer de pulmón de células pequeñas y tumores metastásicos en el pulmón

Lung neuroendocrine tumors encompass an extensive spectrum of lung tumors. They range from neoplasms with lower metastatic potential to others with a high degree of malignancy that represent approximately 19% of all primary malignant bronchopulmonary tumors. The most frequent is small-cell lung carcinoma (79%) followed by large cell neuroendocrine carcinoma (16%) while typical and atypical carcinoids represent the approximately 5% of remaining tumors. In limited stages, the treatment of choice is a combination of cisplatin and etoposide along with concurrent radiotherapy. In advanced disease, the treatment approach is systemic and based mainly on chemotherapy (CT). However, at present, immunotherapy plays an important role in the treatment of microcytic lung carcinoma and was included as first-line therapy together with CT. The lungs are the second most common location of metastatic disease, encompassing all histological types (almost 30% of cases) and are the only site of metastasis in 20% of cases.

Leptomeningeal Disease in Breast Cancer: Pre-Treatment Prognostic Factors and Outcomes

Leptomeningeal disease (LMD) is a devastating diagnosis with limited treatment options and poor prognosis. With recent advances in treatment, women with breast cancer (BC) are living longer and the incidence of LMD in this population is increasing. There remains little data regarding the prognosis and optimal treatment of these patients. As such, we conducted a multi-institutional retrospective review of women with BC LMD and analyzed outcomes based on prognostic factors and treatments.We analyzed the records of women diagnosed with BC LMD via MRIs of their brain and/or spine between 2000 and 2020 at two academic medical centers. Demographic and clinical characteristics were abstracted from electronic medical records and an in-depth radiographic review was performed by a neuro-radiologist for each case. Univariate and multivariate Cox proportional-hazards models were generated to identify factors associated with prolonged survival. Collection and analysis of the data was approved by institutional IRB.We identified 227 women with BC LMD. Prior to developing LMD, most women initially presented with Stage I-III BC (62.1%) with ductal histology (67.0%) and biological subtypes including ER-positive/HER2-negative (56.8%), HER2-positive (17.6%), and triple-negative (22.0%). LMD was first diagnosed a median of 4.6 years (range: 0 to 34.1 years) after the initial diagnosis of BC, and the median age at LMD diagnosis was 54.6 years (range: 29.4 to 84.5 years). At time of LMD diagnosis, 146 (64.3%) women presented with a Karnofsky Performance Status (KPS) ≥ 70, 90 (39.6%) had a preceding parenchymal brain metastasis, and 23 (10.1%) had LMD as their only site of metastatic disease. Radiographically, classical LMD (61.7%) was observed more frequently than nodular-only LMD (13.2%). Brain-only LMD was present in 55.1% of patients, spine-only in 6.1% of patients, and both brain and spine in 38.8% of patients. Median survival from the time of LMD diagnosis was 4.5 months (95% CI: 3.4-7.8). Pre-treatment clinical factors associated with improved survival on univariate analysis included ER-positive/HER2-negative subtype (P = 0.010), KPS ≥ 70 (P < 0.001), LMD as the only site of metastasis (P = 0.004), stable or controlled extracranial metastases (P = 0.042), absence of leukopenia (P = 0.040) and the presence of nodular LMD (P < 0.001). After adjusting for these clinical factors, the receipt of radiation therapy (adjusted hazard ratio [AHR] 0.50, 95% CI: 0.37 - 0.68), systemic therapy (AHR 0.27, 95% CI: 0.19 - 0.38) and intrathecal chemotherapy (AHR 0.49, 95% CI: 0.33 - 0.75) were all associated with improved survival.In one of the largest multi-institutional reviews to date, we found that several pre-treatment clinical factors were significantly associated with improved survival among women with breast cancer LMD. However, despite treatment overall survival remains poor, and there is a need for new, effective therapies.M.G. Milligan: None. A. Aitelli: None. W.A. Mehan: Consultant; Kura Oncology. D.D. Shi: None. D.N. Cagney: Research Grant; Viewray, NhTheraguix. K.S. Oh: None. N. Wang: None. P. Brastianos: Research Grant; Merck, Eli Lily, BMS. Honoraria; Merck, Genentech. Consultant; Angiochem, Dantari Pharmaceuticals, Elevatebio, Eli Lily, Genentech, Pfizer, SK Life Sciences, Tesaro. B. Moy: Research Grant; PUMA biotechnology. N.U. Lin: Research Grant; Genentech, Merck, Pfizer, Seattle Genetics. Consultant; PUMA Biotechnology, Seattle Genetics, Daiichi Sankyo, Astra Zeneca, Denali Therapeutics, California Institute for Regenerative Medicine, Prelude Therapeutics. H.A. Shih: Employee; Dartmouth Hitchcock. Research Grant; AbbVie, NIH. Honoraria; UpToDate. Consultant; Cleveland Clinic. Speaker's Bureau; prIME Oncology. advisory; The Radiosurgery Society. director of clinical operations; Massachusetts General Hospital. clinical operational leader; Massachusetts General Hospital.

Unusual Case of Neuroblastoma with Only Growth Plate Metastasis in Bilateral Lower Limbs on Metaiodobenzylguanidine Scintigraphy.

Neuroblastoma is the most common extracranial solid tumor in childhood developing from primitive neural crest cells. I-131-metaiodobenzylguanidine (MIBG) a norepinephrine analog is highly sensitive and specific to identify primary and distant metastatic sites. We report the case of a 2-year-old female child with progressively increasing abdominal distention. Computed tomography (CT) revealed a large mass lesion involving the right suprarenal region with no hepatic or lymph node metastasis. No obvious skeletal abnormality was detected on the whole-body skeletal survey and Tc-99 m-methylene diphosphonate bone scan to suggest metastasis. I-131-MIBG scintigraphy with single-photon emission computerized tomography-CT showed MIBG-avid primary tumor in a suprarenal location with bilateral lower limbs growth plate as the only site of metastasis.

Multidisciplinary Management of Orbital Metastasis and Survival Outcomes.

To study the multidisciplinary management and survival outcomes of orbital metastasis (OM). All patients with a diagnosis of OM treated during 1999-2019 were included. Clinical data were retrospectively collected and analyzed. The study included 118 patients, 71 females and 47 males, with a median age of 61 years. The most common primary tumor types were breast carcinoma (43 patients), melanoma (17), and lung (13), thyroid (7), renal cell (6), and neuroendocrine carcinoma (6). Ninety-six patients had a known history of cancer at OM diagnosis. The median time from diagnosis of primary cancer to OM was 31 months (range, 0-304). In 22 patients, OM was the first sign of cancer. In 47 patients, the orbit was the only site of metastasis. The most common presenting features were restricted by extraocular motility (77 patients) and proptosis (61). Eight patients had enophthalmos. OM was diagnosed based on clinical history and imaging studies in 81 patients and orbital biopsy in 37. One hundred nine patients were treated with chemotherapy and immunotherapy, 75 with radiation, and 21 with palliative surgical resection. Eighty-two patients died during follow up. The median overall survival (OS) time after diagnosis of OM was 17 months (95% CI: 12-28). OM from renal cell carcinoma was associated with the best and OM from thyroid cancer with the worst OS. Patients with breast cancer had longer median survival (28 months; 95% CI: 15-60) than patients with lung, melanoma, neuroendocrine, or thyroid cancer. In this large series, breast cancer and melanoma were the most common causes of OM. Most patients had a known history of cancer at OM diagnosis and did not require orbital biopsy to confirm the diagnosis. Patients with renal cell carcinoma and breast carcinoma had the best prognosis after diagnosis of OM.

Clinicopathological characteristics and outcomes of 122 patients with colorectal cancer metastasize to the ovary

Objective: To explore the clinicopathological characteristics and prognosis of patients with ovarian metastases from colorectal cancer. Methods: A total of 122 female patients with ovarian metastases from colorectal cancer underwent treatment in Cancer Hospital, Chinese Academy of Medical Sciences between 2010 and 2015 were recruited. The clinicopathological features, treatment details and survival data of these patients were retrospectively analyzed. Kaplan-Maier method was used for survival analysis, log rank test and Cox proportional hazards model were used for prognostic factor analysis. Results: The median overall survival (OS) was 19.7 months. The 1-year, 3-years and 5-years OS rates were 72.1%, 24.7% and 9.9%, respectively. A total of 99 (81.1%) patients underwent oophorectomy. The median OS of patients who underwent oophorectomy was 21.9 months, significantly longer than 10.3 months of patients without oophorectomy (P<0.01). Ovary as the only site of metastasis, primary tumor resection, and oophorectomy were associated with improved survival (all P<0.01). Primary tumor resection and oophorectomy were independent prognostic factors for OS (both P<0.01). Conclusion: Patients with ovarian metastases from colorectal cancer might acquire a survival benefit from surgical resection of the primary tumor and ovaries.

Is resection for noncolorectal, nonneuroendocrine liver metastases justified?

The role of hepatectomy in non-colorectal, nonneuroendocrine liver metastasis (NCNN) is not clearly defined. This study represents a step towards surgical frame-shift as an integral part of treatment pathway in these heterogeneous, arbitrarily treated tumors. It aims to provide answers regarding favorable tumor types and patient profiles for which liver metastasectomy would prove beneficial. Retrospective analysis of prospectively maintained database of hepatectomy in NCNN liver metastasis. A total of 50 patients out of 516 patients underwent liver resection during this period. In 27 patients, the liver metastases presented synchronously whereas the other 23 were metachronous. Median disease-free interval (DFI) was 36 months. Gastrointestinal stromal tumors (GIST) were the most common type of primary malignancy (15, 30%). In 41 patients, the liver was the only site of metastases. At a median follow-up of 32.5 months, 24 patients developed recurrences. Five-year overall (OS) and disease-free survival (DFS) for the entire cohort was 60% and 32%, respectively. Median OS was highest in the breast (93 months) followed by GIST (56 months). Patients with longer DFI showed improved OS. (p = .04). Liver resection for NCNN metastases is safe and feasible in selected patients with good survival outcomes. Longer DFI correlates with better survival.

Exploring an Unfathomed Entiry: A Pooled Analysis of Solitory Skeletal Muscle Metastasis from Head and Neck Squamous Cell Carcinoma.

Skeletal muscle is relatively uncommon site for metastasis in head and neck primary. This study was conducted to report our experience of three such cases and analyze the previously reported cases to assess the overall outcomes and formulate a treatment plan for these patients. We pooled the data extracted on extensive literature review and analyzed. A total of 17 patients were analyzed for this study. All the patients had locally advanced primary and 14/17 developed metachronous metastasis. Median duration to development of metastasis was 8.5months, and 13/17 patients had skeletal muscle as the only site of metastasis. Only 6/13 were treated with aggressive intent, 4 of which who underwent surgical resection had the best survival outcomes. Isolated skeletal muscle metastasis in a head and neck primary is relatively rare, and in future, the research work needs to be taken up afresh, on prospective model, with adequate patient sample, to draw a scientifically valid conclusion.

The incidence of peritoneal carcinomatosis and impact on outcomes in relapsed early T4 colorectal cancer.

73 Background: There is limited data regarding the association between peritoneal carcinomatosis (PC) and clinical outcomes in colorectal cancer (CRC). We examined the incidence of PC and explored the relationship to survival (RFS &amp; OS) in CRC. Methods: The demographic and clinical details of patients with stage II/III CRC referred to a tertiary centre in Western Sydney between 2009-2016 were obtained. Associations between clinical outcomes and baseline prognostic factors were investigated using proportional hazards regression models. The effect of prognostic factors on outcome were examined by tumour stage. Results: 495 patients were identified, 281 (57%) with stage II and 214 (43%) with stage III. Median follow-up was 38 months. 330 (67%) had T3 and 165 (33%) had T4 disease. Median age at diagnosis was 72 years (19 -94). 104 (21%) patients relapsed, 24 (23%) had PC and of those, 6 had PC as their only site of metastasis. 10% (n = 5) with T3 developed PC compared with 35% (n = 19) with T4 disease (P = 0.02). Compared with non-PC, PC was associated with poorer median OS (28 Vs 46 m; p = 0.03). Median RFS for T3 was 16 months, T4, 14 months (NS). Median OS for T3 was 34 months Vs T4 28 months (P = 0.45). Of those with PC relapse, the diagnosis of PC was highest in the first two years post-operatively (88%). 9 patients (38%) with PC died due to bowel obstruction Vs 4 (5%) patients with non-PC relapse (P &lt; 0.01). Poorer OS was associated with PC (HR 1.74; p = 0.03), right sided primary (HR 1.602; P = 0.05), T4 stage (HR 1.69; P = 0.03), LVI (HR 1.95; p &lt; 0.01), N stage (HR 1.51; P &lt; 0.01), and number of metastases at baseline (HR 1.25; p = 0.04). On multivariable analysis right sided primary and T4 stage remained significant. Conclusions: Patients with PC relapse have an 18 month shorter median OS than those with non-PC relapse. Further, PC recurrence is more common in patients with T4 compared with T3 CRC and was the only site of metastatic disease in 7% of relapsed patients with T4 CRC. Consideration for peritonectomy and/or HIPEC should be given for patients with PC metastases. For patients with resected early stage T4 CRC, consideration should be given for surveillance laparoscopy.

Prophylactic HIPEC in pT4 Colon Tumors: Proactive Approach or Overtreatment?

BackgroundThe peritoneum is the second most common site for metastasis in patients with colorectal cancer. Various factors have been studied to identify patients at risk of developing peritoneal carcinomatosis (PC), including T4 tumors. The objectives were to assess the incidence of synchronous and metachronous PC, explore potential risk factors for developing PC as the only site of metastasis, and identify which patients might be candidates for prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsWe conducted a retrospective analysis of 125 patients with pT4 colon cancer who underwent surgery in a single center between January 2010 and December 2014.ResultsOf the 947 colon cancer patients who underwent surgery, 125 (13.2%) were diagnosed with pT4a or b colon carcinoma. The median follow-up was 3.7 years. The overall rate of PC was 34.3%, being synchronous in 12% and metachronous in 22.3% of cases. The 8% and 6% of synchronous and metachronous cases of PC respectively were isolated (single site) metastasis. The incidence of PC was 6.1% at 1 year and 14.5% at 3 years after surgery. pT4 was not found to be an independent risk factor for the development of PC (p = 0.231). Nonetheless, the rate of metachronous PC as a single site of metastasis was higher in patients with pT4 tumors and peritoneal nodules around the primary tumor and/or tumor perforation (p = 0.027) and/or who underwent emergency surgery (p = 0.043) than other patients.ConclusionsConsidering pT4 tumor stage as the only risk factor for the development of PC in deciding whether to administer prophylactic HIPEC would lead to unjustified overtreatment.

Outcome of Omani Women with Breast Cancer-associated Brain Metastases Experience from a University Hospital.

ObjectivesBreast cancer (BC) is the leading cancer among women. Almost 20% of patients develop brain metastases (BM) and die shortly afterward. There is a dearth of data on the survival outcome of BC patients with BM from the Arab world.MethodsConsecutive women diagnosed with BC who developed radiologically-confirmed BM during their illness were identified through the hospital’s electronic patient’s records. Clinicopathological features and treatment outcomes were recorded. Survival was calculated using the Kaplan-Meier method, and factors affecting survival were studied using log-rank analysis.ResultsBetween January 2003 and June 2015, a total of 692 patients were treated for BC at our institute. Forty-eight (6.9%) developed BM. The median age at the diagnosis of BM was 45.2 years. More than half of cohort (54.2%) had HER2 positive disease, while 27.1% had the triple-negative disease. The median time interval between the diagnosis of BC and the development of BM was 21 months, and median survival after development of brain disease was seven months. On univariate analysis, pathological grade, previous systemic treatment, brain as the first site of metastases, brain as the only site of metastases, treatment of BM, systemic treatment after BM, and diagnosis-specific graded prognostic assessment (DS-GPA) score significantly affected survival. On multivariate Cox regression analysis, the brain as the first site of metastases, treatment for brain disease, treatment type, and DS-GPA score significantly affected survival post-BM.ConclusionsOur data indicate that Omani women are diagnosed with BC at a younger age, develop BM earlier, and carry a poor outcome.

Routine chest CT for staging of gastric cancer.

BackgroundInternational guidelines on clinical staging of gastric cancer recommend the use of chest CT for the detection of pulmonary metastases. This study assessed the clinical value of routine chest CT in the staging of gastric cancer.MethodsThis retrospective study included patients identified from the gastric cancer registry of Chang Gung Memorial Hospital, Linkou, Taiwan. All patients who underwent clinical staging between 2008 and 2014 were included. The pattern, site and number of metastases at initial presentation and after surgery with curative intent were evaluated. Pulmonary metastases were defined as multiple small round pulmonary nodules with a random distribution or of variable size.ResultsSome 1669 patients were included, of whom 478 (28·6 per cent) had metastatic disease at clinical presentation. The majority of metastases were to the peritoneum (75·7 per cent of patients) or liver (30·5 per cent), and only 27 patients (5·6 per cent) had pulmonary metastases at presentation, none of which were isolated to the lung. Of these 27 patients, 11 had primary lesions located at the cardia/fundus. In 19 patients the lung metastases were also detected on the staging chest X‐ray. After surgery there were 196 cancer recurrences. Some 15 patients (7·6 per cent) had lung metastasis and this was not the only site of metastases in any patient. The prevalence of lung metastasis at presentation of the disease and after surgery was 1·6 and 1·5 per cent respectively.ConclusionThis study does not support the routine use of chest CT for staging of gastric cancer as isolated pulmonary metastasis in the absence of other metastatic sites could not be detected.

Neoplastic Pericardial Effusion: A Monocentric Retrospective Study.

Background: Neoplastic pericardial effusion (NPE) is a life-threatening condition that can worsen clinical outcome in cancer patients. The optimal management of NPE has yet to be defined because randomized studies are lacking. Objective: We report a retrospective monoinstitutional experience describing characteristics, management and prognostic factors in NPE patients. Design: We reviewed clinical, pathological, and echocardiographic features, therapeutic strategies, and outcome in NPE patients referred to our institute from August 2011 to December 2017. Measurements: Twenty-nine patients with NPE from solid tumors have been identified: 21 lung, 5 breast, and 3 other cancer patients. Results: Median age was 62 years. Most of the patients had Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2 (69%) and a symptomatic NPE (69%). In 52% of patients NPE was detected at first diagnosis of metastatic disease, and in 20% of patients pericardium was the only site of metastases. Most of the patients (62%) received systemic therapy, 28% received combined locoregional and systemic therapy, and 10% received locoregional therapy alone. Median overall survival (OS) from NPE diagnosis was 3.9 months. Patients with PS ≥2 had worse OS than patients with better PS <2 (hazard ratio [HR] 3.56, IC 95% 1.19-10.65, p 0.02). Older age, extrapericardial disease, and NPE at progression showed a trend of association with worse OS. Patients treated with locoregional therapy alone showed the shortest median OS (p 0.05). Conclusions: NPE is related to dismal prognosis. Poor PS significantly worsens survival and influences therapeutic approaches. Randomized studies are required to investigate prognostic factors and appropriate clinical management for patients with NPE.

Partial Splenectomy in a Case of Granulosa Cell Tumour (GCT) with Isolated Splenic Metastasis: A Case Report with Review of Literature

A 50-year-old female, a case of granulosa cell tumour of the ovary, operated multiple times, post-chemotherapy and hormonal therapy, since the last 12 years was detected to have a splenic parenchymal metastasis on follow-up. Owing to poor results with our experience with total splenectomy on two postoperative cases of ca ovary, we decided to perform partial splenectomy. Intraoperatively, the nodule was localised with intra-op USG, during which two additional nodules were found and excised. Final histopathology showed tumour in two of these nodules. Intra-op USG-guided RFA of the spleen lesions with minimally invasive techniques was another option but since the patient had a concomitant incisional hernia we decided to proceed with open approach along with hernioplasty. In English literature, spleen as the only site of metastasis is exceedingly rare. We report the first case of granulosa cell tumour of the ovary which has been treated with partial splenectomy. Carrying out this case successfully leads us to believe that partial splenectomy is a viable option in cases where spleen is the only site of metastasis, which also protects the patient from possible complications of splenectomy.

Brain Metastases from Ovarian Carcinoma: An Evaluation of Prognostic Factors and Treatment.

To review a series of patients with brain metastases from ovarian cancer at a single institution. To describe treatment modalities, their outcomes and to determine prognostic factors. Between January 1995 and December 2014, 25 patients with ovarian cancer brain metastases were treated at The Sheba Medical Center. The medical records were retrospectively reviewed to collect demographic, clinical, and imaging data as well as the information on the treatment modalities used and their outcomes. Mean patient age at the time of brain metastasis diagnosis was 62.7 years. The median interval between the diagnosis of primary cancer and brain metastasis was 42.3 months. Neurologic deficits, headache, and seizure were the most common symptoms. The brain was the only site of metastasis in 20% of the patients. Active ovarian cancer at the time of diagnosis of brain metastasis was observed in half of the patients with systemic disease. Multiple brain metastases were observed in 25% of the patients. We treated 11 patients with surgery plus radiation therapy protocols in various orders: surgery followed by complementary whole-brain radiation therapy (WBRT), surgery followed by stereotactic radiosurgery (SRS), and surgery followed by WBRT and then by adjuvant SRS. Five patients underwent surgery alone and nine patients were treated with radiation alone (WBRT, SRS, or both). Univariate analysis for predictors of survival demonstrated that age above 62.7 years at the time of central nervous system involvement was a significant risk factor and leptomeningeal disease was a poor prognostic factor in reference to supra-tentorial lesions. Multivariate analysis for predictors of survival, however, showed that multiple brain lesions (>4) were a poor prognostic factor, and multivariate analysis of the time to progression revealed that combined treatments of surgery and radiation resulted in longer median periods of progression-free survival than each modality alone. We conclude that the only significant predictors of survival or progression-free survival in our cohort were the number of brain metastases and the treatment modality.

Paraneoplastic syndrome as the presentation of limited stage small cell carcinoma

BackgroundSmall cell lung carcinoma (SCLC) is one of the deadliest forms of lung cancer due to its poor prognosis upon diagnosis, rapid doubling time, and affinity for metastasis. As 60–70% of patients with SCLC have disseminated disease upon presentation, it is imperative to determine the extent of disease burden for treatment. As a neuroendocrine carcinoma, clinicians must pay close attention to abnormal findings in a smoker that could lead to earlier diagnosis and better prognostication.Case presentationA 64 year-old 20-pack year smoker presented to the emergency department with nausea and vomiting for 3 days. No inciting events were elicited. History and review of symptoms were negative including symptoms most-commonly associated with malignancy such as fevers and weight loss. He also denied any pulmonary symptoms. Physical examination was benign except for right lung end-expiratory wheezing. Our patient was clinically euvolemic. Initial blood laboratories showed a sodium 110, serum osmolarity 227, and urine osmolarity of 579. Fluid restriction led to normalization of his sodium and resolution of nausea & vomiting. Chest radiography was obtained to follow-up on the wheezing, which was read as no acute cardiopulmonary disease by radiology. Due to high suspicion of SIADH from malignancy, a CT of the chest was performed which showed a conglomerate of nodules and opacities in the right upper lobe. Biopsy revealed SCLC. At outpatient follow-up, patient had a PET-CT showing one active mediastinal lymph node as the only site of metastasis. He received three round of chemotherapy, chest and prophylactic cranial radiation, and deemed in remission by oncology.Discussion and conclusionsDue to its affinity for metastases, 70% of patients with SCLC present with symptoms related to the spread of cancer to affected organ systems. Given the aggressive nature of this disease, screening measures have been implemented to help diagnose limited stage SCLC. Unfortunately, in our patient and many others, screening guidelines may fail to identify appropriate patients to scan. It is therefore imperative to use our clinical index of suspicion and identify any early presentations (including paraneoplastic syndromes) which may tip off the beginning stages of SCLC. This could improve survival rates by up to 45%.