Median Disease-free Interval Research Articles

Shared DNA-based copy number with divided methylation changes differentiate and clinically associate early stage pancreatic cancer tumors.

434 Background: There is no known molecular taxonomy of pancreatic cancer that can guide therapeutic strategies. Understanding the fundamental molecular mechanism underlying pancreatic cancer biology remains an unmet need. We explore the extent to which combinations of DNA-based molecular changes in copy number (CN) and methylation separate early stage PAAD tumors and associated with survival outcomes. Methods: We performed genome-wide combined cluster analyses on DNA-based CN and methylation changes using TCGA data. We examined cluster associations with clinical outcomes by comparing in months (mos), Kaplan--Meier estimated overall survival (OS) and disease-free interval (DFI) using a log-rank test. We performed additional comparisons among CN-Methylation derived clusters with respect to PAAD phenotypes. Results: Using 78 early stage pancreatic cancer tumors from TCGA with CN, methylation and clinical outcomes data, we identified two patient clusters with distinct gene copy number signatures that when combined with three methylation signatures, resulted in three additional clusters. Thus, the same gene CN signature, when combined with different methylation signatures, further differentiated tumors into sub-clusters with varying levels of associations with clinical outcome. Among them, analogous to current gene-expression based subtypes, we also identified an immune-rich subtype that was associated with improved overall survival (n=21, median OS=16mos; DFI=16mos), and an extracellular matrix (ECM)-rich with worse survival (n=19, median OS=12mos; DFI=8mos). Unlike previous expression subtypes, we identified another metabolic-enriched subtype with the same worse median OS and DFI, differentiated by methylation with the ECM-rich subtype. The improved OS cluster had a signature of CN neutral and increased methylation, while the poor cluster had a signature of CN gains and increased methylation among a set of genes distinct from the improved cluster. No significant differences in age, site, microsatellite instability and KRAS status among clusters were noted. Notably, in a multivariable model that included gene expression-based subtypes, only our DNA-level subtypes remained significantly associated with overall survival. Conclusions: While RNA-level changes often display large variations, DNA-level changes are more robust. Copy number changes appear to separate tumors into poor and improved prognosis clusters, while methylation appears to inform on the further separation of poor prognosis into various levels. A DNA-based molecular taxonomy for early stage pancreatic cancer could prove invaluable when used in combination with methylation-based circulating tumor DNA assays for clinical trial monitoring of tumor responses.

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.

Addressing the contralateral neck for ipsilateral disease recurrence in oral cavity cancers

BackgroundEvidence for performing contralateral neck dissection (CND) of recurrent oral cavity squamous cell cancers (OCSCC) is lacking. Material and methodsThis is a retrospective study of 78 consecutive OCSCC having ipsilateral recurrence recorded over five years. We screened 1658 OCSCC patients and selected those patients who underwent CND as part of treatment for ipsilateral recurrence. ResultsThe median disease-free interval was 32 months. Incidence of contralateral nodal metastasis (CNM) in recurrent OCSCC was 23.1% and of which 14% were occult. The factor significantly influencing CNM was the depth of invasion (DOI) > 10 mm (p < 0.01). In our study, imaging had suboptimal PPV (33%) while it had high NPV (88%) in diagnosing nodal metastasis in recurrent OCSCC. ConclusionDOI is the most important factor predicting CNM in case of ipsilateral primary recurrence. PET-CECT has a high NPV and contralateral neck should be addressed in case of tumours with higher DOI.

Time interval-based indication for liver resection of metastasis from pancreatic cancer

BackgroundSurgical indications for liver metastases from pancreatic ductal adenocarcinoma (PDAC) are lacking because outcomes are usually poor. However, liver resection and the recent progress in perioperative chemotherapy have been observed to improve survival.MethodsWe performed liver resection for liver metastases from PDAC only under the following criteria: (1) liver-only metastasis, (2) up to three tumors, and (3) no increase in the number of metastases during the 3-month observation period. No limitations were placed on the location or size of liver metastasis. In this study, we aimed to validate our surgical criteria and analyze factors affecting survival in patients with PDAC.ResultsSeventy-nine patients underwent curative resection for PDAC between 2005 and 2015. Seventy-one patients experienced recurrence, with liver-only recurrence in 17 patients. Among these, nine patients underwent liver resection and eight did not. The median survival time was significantly better for patients who underwent liver resection (55 months) than for those with other recurrences (17.5 months, p = 0.016). The median survival after liver recurrence was significantly better in the liver resection group (31 months) than in the non-liver resection group (7 months, p = 0.0008). The median disease-free interval (DFI) after pancreatectomy was significantly longer in the liver resection group (21 months; range, 3–44 months) than in the non-liver resection group (3 months; range, 2–7 months; p = 0.02).ConclusionGood indications for liver metastases from PDAC include solitary metachronous tumors and longer DFIs.

Adjuvant doxorubicin vs metronomic cyclophosphamide and meloxicam vs surgery alone for cats with mammary carcinomas: A retrospective study of 137 cases.

This study aims to evaluate the efficacy and side effects of low dose cyclophosphamide chemotherapy plus meloxicam as an adjuvant treatment, compared with high dose doxorubicin or surgery alone in cats with mammary carcinoma. Medical records of 228 female cats treated for mammary carcinoma between 2008 and 2018, were reviewed in eight veterinary institutions. Only cats with complete tumour staging and radical mastectomy were included in the study. One hundred and thirty-seven cats were divided into three treatment groups: group 1 (n=80) cats treated with surgery, group 2 (n=34) cats that had surgery and adjuvant treatment with doxorubicin, and group 3 (n=23) cats with surgery and adjuvant treatment with low dose metronomic cyclophosphamide and meloxicam. The study endpoints were disease free interval (DFI) and overall survival (OS). Toxicity was evaluated according to the VCOG-CTCAE criteria. The median DFI was 270, 226 and 372 days in groups 1, 2 and 3, respectively. The median OS was 338 (group 1), 421 (group 2) and 430 (group 3) days. The differences between groups were not significant (DFI P=.280 and OS P=.186). Toxicity was observed in 52.9% (n=18) of cats in group 2 and 39.1% (n=9) of cats in group 3, with mild to moderate intensity. Differences were not significant (P=.306). In conclusion, adjuvant chemotherapy treatment did not improve survival and the overall benefit remains unproven. Randomized prospective trials are necessary to clarify the effectiveness of adjuvant chemotherapy treatment for feline mammary carcinomas.

Pulmonary metastasectomy for pulmonary metastasis of breast cancer has a limited prognostic impact: a multi-institutional retrospective analysis.

BackgroundPulmonary metastasectomy (PM) for breast cancer-derived pulmonary metastasis is controversial. This study aimed to assess the prognostic factors and implication of PM for metastatic breast cancer using a multi-institutional database.MethodsClinical data of 253 females with pulmonary metastasis of breast cancer who underwent PM between 1982 and 2017 were analyzed retrospectively.ResultsThe median patient age was 56 years. The median follow-up period was 5.4 years, and the median disease-free interval (DFI) was 4.8 years. The 5- and 10-year survival rates after PM were 64.9% and 50.4%, respectively, and the median overall survival was 10.1 years. Univariate analysis revealed that the period of PM before 2000, a DFI <36 months, lobectomy/pneumonectomy, large tumor size, and lymph node metastasis were predictive of a worse overall survival. In the multivariate analysis, a DFI <36 months, large tumor size, and lymph node metastasis remained significantly related to overall survival. The 5- and 10-year cancer-specific survival rates after PM were 66.9% and 54.7%, respectively, and the median cancer-specific survival was 13.1 years. Univariate analyses revealed that the period of PM before 2000, DFI <36 months, lobectomy/pneumonectomy, large tumor size, lymph node metastasis, and incomplete resection were predictive of a worse cancer-specific survival. Multivariate analysis confirmed that a DFI <36 months, large tumor size and incomplete resection were significantly related to cancer-specific survival.ConclusionsAs PM has limited efficacy in breast cancer, it should be considered an optional treatment for pulmonary metastasis of breast cancer.

Expanded indications for lung transplantation for pulmonary complications after hematopoietic stem cell transplantation

ObjectivesPulmonary complications after hematopoietic stem cell transplantation (HSCT) are associated with poor survival and can be treated by lung transplantation (LT). However, the indications for LT in patients with pulmonary complications after HSCT remain unclear due to low number of cases. HSCT is frequently conducted for hematologic malignancies, which have different recurrence patterns from solid-organ malignancies. Some patients also experience ABO blood type changes post-HSCT. This study aimed to reassess the indication of LT for pulmonary complications post-HSCT, focusing on disease-free interval (DFI) and ABO-incompatibility. MethodsRetrospective chart reviews were performed in patients who underwent LT for post-HSCT pulmonary complications. In patients with previous hematologic malignancy, indication was based on estimated recurrence rate instead of DFI. Donors were selected based on the recipient anti-A/B antibody profile rather than ABO type. Post-LT survival and complication rates were examined. ResultsForty consecutive patients undergoing LT after HSCT (including 31 with previous hematologic malignancy) were analyzed. The median DFI between HSCT and LT was 64.5 months. Thirteen patients with previous hematologic malignancy had DFI <5 years but none experienced recurrence. There was no significant difference in 5-year post-LT survival between patients undergoing (74.7%) and not undergoing HSCT (68.4%). There was no significant difference in survival between patients with DFI ≥5 years (63.8%) and patients with DFI <5 years (83.3%). Five patients underwent LTs from major ABO-incompatible donors, but none developed incompatibility-related complications. ConclusionsIndications based on estimated recurrence rates and recipients' anti-A/B antibody profiles may increase the use of LT for patients after HSCT.

Salvage of Locally Recurrent Breast Cancer with Repeat Breast Conservation Using 45Gy Hyperfractionated Partial Breast Re-Irradiation

Mastectomy has long been the preferred approach for local salvage of recurrent breast cancer following breast conservation therapy (BCT). Growing interest in avoiding mastectomy prompted RTOG 1014, a landmark phase 2 study demonstrating the feasibility of repeat BCT using a novel radiotherapy (RT) regimen (i.e. 45Gy administered in thirty fractions of 1.5Gy twice-daily to the partial breast, “rePBI”). We adopted this regimen as our institutional standard and report our experience to test the hypothesis that rePBI is safe and effective as salvage therapy. All patients at our institution who underwent repeat BCT from 2011-2019 were identified. Patients with invasive or in situ breast cancer who received rePBI were included. Clinicopathologic features and treatment characteristics for both primary breast cancers and recurrences were collected, as were rates of subsequent recurrence and treatment-associated toxicities. The cohort included 34 patients with a median age of 65.8 years (range 46.2 – 78.2) at the time of rePBI. At initial BCT, 12 (35%) had in-situ disease and 22 (65%) had invasive breast cancer with a median tumor size of 1. 2 cm (range 0.2 – 4.2 cm). Median whole breast RT dose was 48.6 Gy (range 42.4 – 54 Gy) and 27 (79%) received a boost to the lumpectomy cavity. At the time of local recurrence and salvage with BCT using rePBI, 9 (27%) patients presented with in-situ disease and 25 (73%) had invasive histology of which 28 (82%) were ER+, 19 (56%) were PR+, and 2 (6%) were HER2+. The median disease-free interval between primary and recurrence was 9.8 years (range 1.4-27.2) and median tumor size was 0.8 cm (range 0.1 – 3.5 cm). As part of the salvage regimen, 19 (56%) patients received endocrine therapy and 9 (27%) received chemotherapy or targeted therapy. At a median follow-up after rePBI of 23.5 months, there were two subsequent locoregional recurrences: one patient had another in-breast recurrence and underwent mastectomy (the only mastectomy in the cohort to date), the second patient had a regional recurrence and underwent axillary dissection followed by regional nodal irradiation. The overall rate of adverse events was low, with no grade ≥3 toxicity. The most common acute toxicity (< 3 months) was radiation dermatitis of grade 1 or 2, experienced by all patients. Late toxicities (> 3 months) included grade 1 or 2 fibrosis in 14 (41%), breast asymmetry in 12 (35%), chest wall pain in 11 (32%), lymphedema in 4 (12%), shoulder range of motion limitation in 3 (9%) and telangiectasia in 2 (6%). Repeat breast conservation using the hyperfractionated partial-breast RT regimen defined by RTOG 1014 (45Gy administered in thirty 1.5Gy twice-daily fractions) appears effective and well-tolerated. None of the patients in this cohort exhibited grade 3 or higher toxicity and subsequent local control was excellent. Longer term follow-up among larger cohorts will define whether salvage mastectomy should remain the preferred standard.

Stereotactic Ablative Radiotherapy (SABR) in Oligometastatic and Oligoprogressive Gynecologic Cancers: Clinical Outcomes of a Single Institution Analysis

The role of stereotactic ablative radiotherapy (SABR) for gynecologic malignancies has not been clearly defined despite recent clinical uptake. This study evaluates the outcomes of SABR in patients with metastatic gynecologic cancer at a single institution. Patients with gynecologic cancers treated from 2009-2019 were extracted from an institutional SABR database. Descriptive statistics were used to report patient and treatment characteristics, toxicity and chemotherapy-free interval. Local recurrence free survival (LRFS), distant progression-free survival (DPFS), and overall survival (OS) probabilities were calculated using Kaplan-Meier methods. The relationship of primary site, tumor grade, dose of radiotherapy, and disease-free interval (DFI) to LRFS and DPFS were assessed using Cox regression methods for multivariable analysis (MVA). One hundred nine lesions in 77 patients with gynecologic cancer were treated with SABR. Median age was 63 and follow up after SABR was 16.4 months (1-79.6). Patients were treated with SABR for oligoprogressive disease (n = 58), oligometastatic disease (n = 34), or for local progression in critical areas (n = 17). Primary site included cancers of the endometrium (n = 36), cervix (n = 19), ovary (n = 15), and vulva or vaginal (n = 7). Median DFI was 22.3 months (1.6-143.3) from diagnosis to metastasis. Treatment was delivered to lesions in the lung (n = 25), pelvis (n = 23) spine (n = 17), para-aortic (n = 16) and distant nodes (n = 7), abdominal organs (n = 13), and bone (n = 8). Radiotherapy doses ranged from 25-60Gy (median 35Gy) in 2-5 fractions. Patients had between 1 and 6 lesions treated. Thirteen lesions recurred locally (11.9%) at a median of 7.6 months (range 0.5-17.6), and 76% of patients eventually had a distant recurrence after SABR. Median DPFS was 7.8 months (95% CI 3.6-11.9), and OS 31.5 months (95% CI 12.2-45.7). At 2 years, LRFS was 77.6%, DPFS was 19.6%, and OS was 51.9%. Thirty-two patients eventually required chemotherapy at median 6 months (range 1-37). There were no grade 3-5 acute or late toxicities reported. On MVA, primary site, tumor grade, dose of radiotherapy and DFI were not significantly associated with LRFS or DRFS. This cohort of patients had excellent LRFS and DPFS when treated with SABR for oligoprogressive, oligometastatic and locally progressive disease. SABR also has the potential to delay time to chemotherapy in patients with gynecologic cancers. Prospective multi-center trials will be critical to establish which primary disease sites and characteristics procure the greatest benefit from SABR use, to delineate optimal dose regimens, and to define the ideal time to implement SABR with other oncologic treatments.

Recurrent cervical cancer treated with palliative chemotherapy: real-world outcome.

IntroductionCervical cancer is the third most common cancer in India. There is limited data on the treatment of relapsed cervical cancer from India; therefore, we report the outcomes of patients with recurrent cervical cancer who were treated with palliative chemotherapy (CT).Materials and methodsThis was a retrospective study of patients with recurrent cervical cancer who received palliative CT from January 2012 to December 2016. The demographic details, clinical profile and survival outcomes were collected. Patients were treated with carboplatin or paclitaxel and carboplatin. Local radiation was given for symptomatic patients. Patients were assessed for responses clinically and/or radiologically after three and six cycles of CT. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier method.ResultsForty-six patients with recurrent cervical cancer were included in this analysis, with a median follow-up of 9.4 months. The median age was 49.5 (25–65) years and the median disease-free interval was 31.3 (2–196) months. Biopsy confirmation of relapse was established in 63%. The median number of CT cycles was six. Twenty-four (52.2%) patients completed six cycles of CT. The overall response rate was 56.5%. Patients with a complete or a partial response were more likely to have PFS > 6 months (p < 0.0001). Median PFS and OS were, respectively, 8.4 (95% CI 6.1–10.7) months and 10.3 (95% CI 6.8–13.8) months. The completion of all cycles of CT and the site of metastasis (nodal vs. visceral or combined) were found to be associated with OS.ConclusionPalliative CT with paclitaxel carboplatin is a safe and effective option in Indian patients with recurrent cervical cancer, with more than half of the patients completing the prescribed CT. Further prospective trials may be required to place this treatment in the right context, in this era of immunotherapy and targeted therapy. However, knowing the outcomes in our population and prognostic factors will help in better prognostication of patients, thereby channelling our limited resources where necessary.

Management of Deep Margin Involvement and or Perineural Invasion in Cutaneous Squamous Cell Carcinoma in the Head and Neck in a Single Unit: 12 Years’ Experience

INTRODUCTION: The eighth edition of American Joint Committee on Cancer guidelines separated cutaneous squamous cell carcinoma in the head and neck (cHNSCCs) into its own entity within head and neck malignancies with the aim of improving tumor risk stratification. The lack of precise prognostic estimates for cHNSCCs prevents clear guidance on the clinical approach to cHNSCCs resulting in heterogeneity of management. OBJECTIVE: Detailed review of the historical management of cHNSCCs in a single tertiary skin cancer center with the aim of creating a treatment algorithm that provides guidance in selecting the appropriate workup and treatment while minimizing unnecessary treatment and resulting morbidity. METHODS: Retrospective review of our institutional pathology database from January 2007 to December 2019 of all recorded head and neck cutaneous lesions excised by St Helens & Knowsley Teaching Hospitals NHS Foundation Trust Plastic Surgery Department. Primary outcomes include recurrence rates and cHNSCC-related mortality. RESULTS: A total of 442 lesions of cHNSCCs from 216 patients excised from the head and neck region were excised during the study period and 164 cHNSCCs had deep margin involvement ± perineural invasion. Median age was 78 years (49–98 years). Median follow-up was 23 months (0–153 months), 9 patients (4%) were lost to follow-up. Seven patients (3%) died before their first 3-monthly follow-up appointment was due. Thirty-nine patients (18%) were immunosuppressed, 10 were solid organ transplant recipients. One hundred thirteen patients (52%) were deceased at the time of review, 25 (22%) died directly or from complications of cHNSCCs. Out of 164 cHNSCCS, majority had deep margin involvement (77%, n = 126), 21% (n = 35) had both deep margin and perineural involvement. Only 5 patients (3%) had cHNSCCs with features of perineural invasion but adequate margins. Forty-five patients (27.4%) in the positive cohort (deep margin involvement ± perineural invasion) went on to develop local, regional, or distant recurrence with a median disease-free interval of 7.7 months (0.5–58 months). Overall recurrence rate was 14.5% (n = 64/442) with a false-negative rate of 6.8% (n = 19/278), The scalp was the most common primary tumor site to recur (45%), followed by the ear (27%) and face (23%). Fifty percent of primary tumors that recurred were moderately differentiated compared with 19% which were poorly differentiated. CONCLUSIONS: Our study demonstrates increased recurrence risk of both scalp and ear cHNSCCs, which warrant calls for more aggressive surgical measures, that is, primary excision with a wide margin down to periosteum with flap reconstruction with adjuvant radiotherapy. Routine sentinel lymph node biopsy in high-risk cHNSCCs could play a role in locoregional control.

Feasibility of neoadjuvant and adjuvant intraperitoneal chemotherapy in patients with advanced epithelial ovarian cancer: A single-center experience.

Intraperitoneal (IP) chemotherapy is believed to prolong the survival of patients with advanced ovarian cancer after primary debulking surgery. However, there is little knowledge about IP chemotherapy in the setting of neoadjuvant chemotherapy, and there are contradictory conclusions about adjuvant IP chemotherapy. Here, we evaluated the feasibility of neoadjuvant and adjuvant IP chemotherapy in patients with advanced epithelial ovarian cancer (AEOC).We retrospectively reviewed the data of 114 patients with AEOC who received neoadjuvant chemotherapy followed by laparoscopic conservative interval debulking surgery (NACT + LIDS) in our institution from January 1, 2009 to December 31, 2017.The median overall survival (OS) was 56 months and the median disease-free interval (DFI) was 14 months for the entire study population. Neoadjuvant IP chemotherapy cycles were crucial for the treatment of no gross residual (R0) disease (hazard ratio [HR] = 0.446, 95% confidence interval [CI] = 0.245–0.811), which was independently associated with OS of the entire study population (HR = 9.589, 95% CI = 3.911–23.507). In addition, residual disease and body mass index (BMI) were the prognostic factors for DFI (HR = 6.022, 95% CI = 3.632–9.986; HR = 1.085, 95% CI = 1.012–1.163). However, adjuvant IP cycles along with BMI were the determining factors for DFI in the R0 group (HR = 0.703, 95% CI = 0.525–0.941; HR = 1.130, 95% CI = 1.025–1.247), and were associated with OS in the R0 group (HR = 0.488, 95% CI = 0.289–0.824). The OS and DFI Kaplan-Meier curves stratified by adjuvant IP chemothearpy cycles within the R0 group were statistically significant (P = .024 and P = .033, respectively).Our results showed improvement in patients with AEOC in terms of survival, thus suggesting the feasibility of neoadjuvant and adjuvant IP chemotherapy.

Analysis of prognostic factors in patients with lymph node recurrence after radical esophagectomy: importance of locoregional therapy.

Lymph node (LN) recurrence is frequently encountered in esophageal cancer. The aim of this study was to determine the effects of various factors, including loco-regional treatment of LN-only recurrence, on the survival rate. Among 941 patients who underwent curative resection for esophageal squamous cell carcinoma in 2003-2016, we retrospectively reviewed 117 patients (12.4%) who developed LN-only recurrence. One, 2, 3, and 4 or more metastatic LNs were found in 72, 22, 6, and 17 patients, respectively, after a median disease-free interval of 8.4months (range 1.1-62.0). Among all cases, recurrence was out of the surgical field in 53 cases (45.3%). Recurrent LNs were controlled by loco-regional treatment in 29 (43.9%) and by chemotherapy alone in 3 patients (7.0%). The 3-year survival rates of patients who did and did not achieve local control were 53.2% and 5.2%, respectively. Univariate analysis showed significant relationships between post-recurrence survival rate and pStage I-II at initial surgery, no history of radiotherapy, recurrence in ≤ 2 LN, and loco-regional treatment of LN recurrence. Multivariate analysis identified recurrence in ≤ 2 LN (HR 0.3169, 95% CI 0.1023-0.5314, p = 0.0038) and loco-regional treatment (HR 0.1973, 95% CI 0.0075-0.3871, p = 0.0416) as the only two significant and independent prognostic factors of survival. Recurrence limited to ≤ 2 LN and loco-regional treatment (chemoradiotheapy or surgery) for LN recurrence were associated with favorable survival of patients with history of radical esophagectomy followed by LN recurrence. Our results emphasize the importance of local control of LN recurrence regardless of location.

Non-surgical Treatments for Lung Metastases in Patients with Soft Tissue Sarcoma: Stereotactic Body Radiation Therapy (SBRT) and Radiofrequency Ablation (RFA).

Radio-frequency ablation (RFA) and Stereotactic Body Radiation Therapy (SBRT) are two emerging therapies for lung metastases. Aliterature review was performed to evaluate the outcomes and complications of these procedures in patients with lung metastases from soft tissue sarcoma (STS). After selection, seven studies were included for each treatment encompassing a total of 424 patients: 218 in the SBRT group and 206 in the RFA group. The mean age ranged from 47.9 to 64 years in the SBRT group and from 48 to 62.7 years in the RFA group. The most common histologic subtype was, in both groups, leiomyosarcoma. In the SBRT group, median overall survival ranged from 25.2 to 69 months and median disease- free interval was from 8.4 to 45 months. Two out of seven studies reported G3 and one G3 toxicity, respectively. In RFA patients, overall survival ranged from 15 to 50 months. The most frequent complication was pneumothorax. Local control showed a high percentage for both procedures. SBRT is recommended in patients unsuitable to surgery, in synchronous bilateral pulmonary metastases, in case of deep lesions and patients receiving high-risk systemic therapies. RFA is indicated in case of a long disease-free interval, in oligometastatic disease, when only the lung is involved, in small size lesions far from large vessels. Further large randomized studies are necessary to establish whether these treatments may also represent a reliable alternative to surgery.

Outcomes of surgical resection for pulmonary metastasis from ovarian cancer

BackgroundDue to its rarity, information on pulmonary metastasectomy for pulmonary metastasis from ovarian cancer is limited.MethodsCases of pulmonary metastasectomy for ovarian cancer were collected in a multi-institutional setting and the outcomes were analyzed.ResultsAmong 1508 cases in which pulmonary resection was performed to treat pulmonary metastasis from tumors of various organs, 6 cases (0.4%) involved pulmonary metastasis from ovarian cancer. The mean age was 61 years (range, 39–75 years). The histological types were undifferentiated carcinoma in 2 patients, and clear cell adenocarcinoma, serous papillary cystadenocarcinoma, serous adenocarcinoma, and endometroid adenocarcinoma in 1 patient each. One patient (17%) had a history of liver metastasis at the time of pulmonary resection. The median disease-free interval was 22 months (range, 0 [synchronous]-188 months). The tumor was solitary in 5 patients (83%). The mean tumor size was 15 mm (range, 5–23 mm). All 6 patients underwent complete resection. The type of resection was wide wedge resection in 3 patients, segmentectomy in 2 patients, and lobectomy in 1 patient. Four patients (67%) received postoperative chemotherapy. Thus far, 4 patients (67%) have experienced recurrence after pulmonary resection. In terms of outcomes, 1 patient who had synchronous pulmonary metastasis with the primary tumor died in the early period after pulmonary resection, 1 patient is alive without recurrence after a short follow-up period (5 months), 3 patients have achieved mid- to long-term survival and are alive with disease (38–61 months), and 1 patient achieved long-term (61 months) disease-free survival.ConclusionsPatients with pulmonary metastasis from ovarian cancer who fulfill the eligibility criteria for pulmonary metastasectomy are rare. Pulmonary metastasectomy for ovarian cancer can provide favorable outcomes in highly selected patients. Patients with synchronous pulmonary metastasis from ovarian cancer are not good candidates for pulmonary metastasectomy.

LOPH: a novel chemotherapeutic protocol for feline high-grade multicentric or mediastinal lymphoma, developed in an area endemic for feline leukemia virus.

The aim of this study was to establish the safety and efficacy of a novel multidrug lomustine-based chemotherapeutic protocol for cats with high-grade multicentric or mediastinal lymphoma, in an area endemic for feline leukemia virus (FeLV). This prospective study included owned cats, diagnosed (cytologically) with multicentric or mediastinal lymphoma and treated with the LOPH (lomustine, vincristine [Oncovin; Antibióticos do Brasil], prednisolone and hydroxydaunorubicin [doxorubicin]) protocol. A complete blood count was performed before every chemotherapy session and any significant abnormalities recorded as possible related toxicities. Median survival time (MST) and disease-free interval were estimated by Kaplan-Meier curves. Twenty-one cats were included in this study. Nineteen (90.5%) tested positive for FeLV and were therefore considered to have persistent viremia. Complete response was reported in 81% (n = 17/21), while three had partial remission and one had no response. Seven cats finished the induction protocol within 20-31 weeks (23.1 ± 4.5; median 20) and all seven received a maintenance protocol. The MST (lymphoma-related survival) for the 21 cats was 214 days. The MST was 214 days for cats with mediastinal lymphoma (n = 13), but it was not reached for multicentric lymphoma (n = 8; P = 0.9). The MST of cats with persistent FeLV antigenemia was 171 days. Grade I anorexia and vomiting occurred in 19% of the cats (n = 4/21). Hematologic toxicity was found in 100% of the cats at some point during their treatment, but it was mostly grade I or II. Neutropenia, thrombocytopenia and anemia occurred in 16/21, 21/21 and 15/21 cats, respectively. The LOPH protocol was well tolerated by cats with lymphoma and persistent FeLV viremia, and resulted in a better MST than similar studies with other protocols. Novel studies and controlled trials are necessary in order to evaluate the efficacy of different protocols according to the lymphoma subtype, anatomic form and FeLV status.

Prognostic Indicators and Clinical Outcome in Dogs with Subcutaneous Mast Cell Tumors Treated with Surgery Alone: 43 Cases.

The purpose of this study was to determine if clinical findings, histologic grade, or other histologic features were associated with clinical outcome in dogs with subcutaneous mast cell tumors (MCTs). Medical records of 43 client-owned dogs were retrospectively reviewed, and follow-up information was gathered via phone or follow-up examination. Progression-free survival (PFS), disease-free interval (DFI), and overall survival were calculated. Forty-two and twenty-two dogs, respectively, had grade 2 (Patnaik grading system) or low-grade tumors (two-tier grading system). Median PFS was 1474 days. Median DFI was not reached at >1968 days. Overall median survival time was not reached at >1968 days. In univariate analysis, argyrophilic nucleolar organizer regions (AgNORs), proliferating cell nuclear antigen, and mitotic index were negatively prognostic for PFS whereas Ki-67, proliferating cell nuclear antigen, and microvessel density were negatively prognostic for DFI. In multivariate analysis, AgNORs remained negatively prognostic for PFS. Results suggest that proliferation indices, especially AgNORs, may be useful in predicting the rare poor outcomes in dogs with subcutaneous MCTs. The vast majority of subcutaneous MCTs appear to be low or intermediate grade with excellent outcomes from good local tumor control.

SAT-171 Adrenocortical Carcinoma in Thailand: A 10-Year Retrospective Review in a Single Tertiary Center

Background: Adrenocortical carcinoma (ACC) is a rare and fatal endocrine malignancy. This retrospective review aims to investigate treatment outcomes and clinical characteristics of 18 patients diagnosed with ACC at King Chulalongkorn Memorial Hospital from 2009 to 2018. Methods: We reviewed medical records regarding the presenting symptoms, hormonal investigations, imaging results, staging, modalities of treatment and outcomes. Results: Of the 18 patients, 14 patients were female (77%). The median age at diagnosis was 47.5 years [interquartile range (IQR) 39.5-58.2]. Mass effects and/or hormonal hypersecretion were the most common presentation, documented in 7 (38%) and 6 (33%) patients respectively. Autonomous adrenal hormone excess was found in 10 patients (56%). Cushing’s syndrome and elevated dehydroepiandrosterone sulphate (DHEAS) were documented in 9 (50%) and 7 patients (41%) respectively. Mineralocorticoid excess was found in 1 patient (6%). At initial staging, 9 patients (50%) were in advance or metastatic stage. Surgery was performed in 17 patients (94%) and 13 patients (76%) were in remission. However, recurrence was observed in 6 patients (33%), with the median disease-free interval of 13.5 months (IQR 12.0-25.0 months). In patients with stage 2 disease, open surgery resulted in longer disease-free interval despite larger tumor size, compared with laparoscopic surgery. Final outcomes revealed that 8 patients (44%) had remission, 2 patients (11%) had persistent disease and 6 patients (33%) died. Combination therapy (adrenalectomy, radiation, medications and local control such as metastatectomy, radiofrequency ablation and transarterial chemoembolization) was documented in 11 patients (61%). All patients with remission received complete tumor resection and presented at early stages of cancer, with the majority of them having non-functioning tumors. The median follow-up time was 34 months (IQR 9-73). Conclusions: ACC is a rare and fatal disease with high mortality rates. Diagnosis is time-sensitive and requires multimodality approach.

Long-Term Outcomes of Pulmonary Metastasectomy for Uterine Malignancies: A Multi-institutional Study in the Current Era

BackgroundInformation on pulmonary metastasectomy (PM) for uterine malignancies in the current era is limited. In the present study, we analyzed the clinical course and results of PM for uterine malignancies in the era of modern imaging diagnostics to clarify the role of PM in the current era in a multi-institutional setting.MethodsFifty-seven patients who underwent PM for uterine malignancies between 2006 and 2015 were retrospectively reviewed. The short- and long-term outcomes, along with factors associated with the prognosis, were analyzed. Details of the clinical course after PM were described.ResultsThe mean age of patients was 59.4 years. The primary tumor was located in the uterus corpus in 34 cases (60%) and in the uterus cervix in 23 cases (40%). The median disease-free interval (DFI) was 32 months. Forty patients (70%) received fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography before PM, and complete resection was achieved in 52 patients (91%). Postoperative complications occurred in 4 patients (7%). Of the 52 patients who underwent complete resection of pulmonary metastases, 28 experienced recurrence, and among these, 17 (60%) underwent local therapy, including six repeat PMs. Among the 52 patients who underwent complete resection, the 5-year relapse-free survival rate was 40.7% and the 5-year overall survival (OS) rate was 68.8%. The univariate analysis revealed that a DFI of ≤ 24 months was associated with significantly poorer OS.ConclusionsPM for uterine malignancies is safe and provides favorable long-term outcomes in selected patients. Patients with a DFI of > 24 months have better OS and are good candidates for PM.

Primary Sarcoma of the Lung - Prognostic Value of Clinicopathological Characteristics of 26 Cases.

Primary sarcomas of the lung (PSL) represent a rare, largely unknown entity. We herein present a retrospective study of 26 patients diagnosed with PSL. For a period of 10 years, the records of patients from 5 centers were gathered and analyzed. Median age at diagnosis was 61.96 years (range=31-75 years). Eight patients (33.33%) had mediastinal node invasion (MNI). From 17 patients (70.83%) with localized disease, 11 patients (64.70%) underwent surgery. Recurrence rate was 72.72%. Median disease-free interval was 15 months. The median overall survival (OS) of patients with metastatic disease was 4 months and 10 months for the whole population. Only surgery had an impact on survival. Prognosis of PSL is somber. The high proportion of patients with MNI at diagnosis may serve as an indication for surgical evaluation of mediastinum and raises the question whether patients with locoregional PSL should be treated with a more aggressive approach.