Melanoma at ASCO20: Shortening, Changing, and Repurposing Therapeutics in Patients With Unresectable Disease

The aim of this study was to measure the serum level of the tumour markers CA 195 and CEA in patients with either colorectal or pancreatic cancer both before and at serial intervals after operation. CA 195 and CEA were measured in 199 patients with colorectal cancer and 52 patients with pancreatic cancer. The median concentrations of CA 195 were 3.0 u/ml (interquartile range 3.0-4.5 u/ml) in patients with a Dukes’ stage A lesion, 5.8 u/ml (3.0-18.2 u/ml) in patients with a Dukes’ stage B lesion, 6.1 u/ml (3.0-24.7 u/ml) in patients with a Dukes’ stage C and 23.8 u/ml (11.1-409.0 u/ml) in patients with metastatic disease (normal range 0-7 u/ml). The median levels of CEA were 2.6 ng/ml (1.7-3.3 ng/ml) for Dukes’ stage A, 3.3 ng/ml (1.7-7.2 ng/ml) for Dukes’ stage B, 3.7 ng/ml (2.2-7.9 ng/ml) for Dukes’ stage C and 34.5 ng/ml (13.3-289.4 ng/ml) for metastatic disease. A rising level of CA 195 or CEA after operation suggested recurrence of the tumour. In none of these patients was the recurrence operable. In patients with pancreatic adenocarcinoma, the level of CA 195 was significantly higher in patients with metastatic disease but it did not discriminate between resectable and unresectable disease. The duration of survival correlated with the initial level of CA 195 (Rs = –0.66, p < 0.001).

Download Full-text

Outcomes of treatment of carcinoma gall bladder undergoing curative intent surgery.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15621 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15621-e15621

Author(s):

Arun Chaturvedi ◽

Vijay Kumar ◽

Sameer Gupta ◽

Naseem Akhtar ◽

Shiv Rajan Saini ◽

...

Keyword(s):

Gall Bladder ◽

Frozen Section ◽

Tertiary Care ◽

Surgical Oncology ◽

University Hospital ◽

North India ◽

Curative Intent ◽

Adjacent Organ ◽

Radical Cholecystectomy ◽

Unresectable Disease

e15621 Background: Gall bladder carcinoma (GBC) is the most common malignancy of the biliary tract. North India reports one of the highest incidences of GBC in the world. Majority of patients present with advanced disease where surgery is not possible. We report the results of patients undergoing curative intent surgery at a tertiary care University hospital in North India. Methods: Data of 270 patients undergoing curative intent surgery for GBC at the Department of Surgical Oncology, King George’s Medical University, Lucknow (India) between January 2014 and December 2018 was retrospectively studied. We have analysed the collected data using descriptive and survival statistics. Results: During the period of study 270 patients were operated for GBC. Mean age of patients was 50.2 years and majority (75.2%) were females. On surgical exploration 82 (30.4%) had unresectable disease and only a biopsy or palliative procedure was done. Simple cholecystectomy was done where frozen section showed benign calculus cholecystitis in 26 (9.6%) patients. Radical cholecystectomy was performed in 162 (60%) patients. Final histopathology revealed Xanthogranulomatous cholecystitis in 28 (17.3%) of these 162 patients. Adjacent organ resection was done in 29 of the 134 (24.1%) patients undergoing radical cholecystectomy for pathologically proven GBC. Colon and CBD were the most common adjacent organs resected. Completion radical cholecystectomy was done in 22 patients with incidental GBC. Adjuvant chemotherapy as per our institutional protocol was given to 68 (50.7%) patients having Stage 3 or more disease. After a mean follow-up of 19 months the median disease free interval (DFI) is 38 months and the median overall survival (OS) has not been reached. Patients undergoing adjacent organ resection had an inferior median OS of 20 months compared to those without it where the median has not been reached (Log Rank P = 0.006). Conclusions: Nearly a third of GBC patients planned for curative intent surgery are found to have unresectable disease on exploration. This proportion needs to be brought down. Radical cholecystectomy in properly selected GBC patients without adjacent organ involvement gives satisfactory survival outcomes.

Download Full-text

A Phase 2 Study of Combined Chemo-Immunotherapy with Cisplatin-Pembrolizumab and Radiation for Unresectable Vulvar Squamous Cell Carcinoma

10.21203/rs.3.rs-37030/v1 ◽

2020 ◽

Author(s):

Oladapo Yeku ◽

Andrea L Russo ◽

Hang Lee ◽

David Spriggs

Keyword(s):

Radiation Therapy ◽

T Cell ◽

Locally Advanced ◽

Standard Of Care ◽

Immune Checkpoint Blockade ◽

Cytotoxic T Cell ◽

Unresectable Disease ◽

Hpv Status ◽

Rare Malignancy ◽

Vulva Cancer

Abstract Purpose: Unresectable or metastatic vulva cancer has relatively poor outcomes despite chemotherapy-sensitized radiation therapy and combination cytotoxic therapy. Despite the virus-associated and immunogenic nature of this disease, novel immunotherapy options that exploit this advantage are currently lacking. Platinum agents such as cisplatin have been shown to prime dendritic cells for T-cell costimulation, promote downregulation of inhibitory checkpoint molecules, and sensitize tumor cells to cytotoxic T-cell killing. Radiation therapy has also been shown to promote immunogenetic cell death as monotherapy and in combination with cisplatin. In combination with pembrolizumab, cisplatin-sensitized radiation is hypothesized to increase overall response rates and recurrence-free survival in patients with vulva cancer, via induction of an anti-tumor inflammatory response.Methods: We propose a single-arm phase II clinical trial of pembrolizumab combined with cisplatin-sensitized radiation therapy for women with unresectable, locally advanced, or metastatic vulva cancer. The first three patients with locally advanced or unresectable disease will receive cycle 1 of pembrolizumab followed by a break and resumption of pembrolizumab at cycle 4 and as part of a safety cohort. All other patients, including the fourth patient with locally advanced/unresectable disease, will receive weekly cisplatin and pembrolizumab every 3 weeks, concurrently with daily radiation therapy. Following the completion of Cis-RT, patients will continue pembrolizumab maintenance for a total of 12 cycles. Archived tissue will be used for HPV status, MSI status, PD-L1, and TIL stratification post-hoc. Imaging will be performed at baseline and every 3 cycles (21-day cycles) as per standard-of-care. Laboratory analysis will occur on the first day of each cycle. Discussion: The combination of cisplatin-sensitized radiation and immune checkpoint blockade has not been evaluated in the upfront setting for vulvar cancer. In this rare malignancy, there are limited interventional clinical trials. This trial is designed to be as accessible as possible by allowing patients to receive cisplatin and radiation locally according to accepted standard-of-care while receiving pembrolizumab and adverse event monitoring at a centralized site. A robust suite of translational correlative studies has also been built into the trial to evaluate tumor-directed immune activation. Trial registration: NCT04430699

Download Full-text

BRAZILIAN CONSENSUS FOR MULTIMODAL TREATMENT OF COLORECTAL LIVER METASTASES. MODULE 3: CONTROVERSIES AND UNRESECTABLE METASTASES

ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) ◽

10.1590/0102-6720201600030011 ◽

2016 ◽

Vol 29 (3) ◽

pp. 173-179 ◽

Cited By ~ 4

Author(s):

Orlando Jorge Martins TORRES ◽

Márcio Carmona MARQUES ◽

Fabio Nasser SANTOS ◽

Igor Correia de FARIAS ◽

Anelisa Kruschewsky COUTINHO ◽

...

Keyword(s):

Liver Disease ◽

Liver Resection ◽

Liver Metastases ◽

Multimodal Treatment ◽

Colorectal Liver Metastases ◽

Hepatic Disease ◽

First Line ◽

Unresectable Disease ◽

Unresectable Metastases ◽

Line Chemotherapy

ABSTRACT In the last module of this consensus, controversial topics were discussed. Management of the disease after progression during first line chemotherapy was the first discussion. Next, the benefits of liver resection in the presence of extra-hepatic disease were debated, as soon as, the best sequence of treatment. Conversion chemotherapy in the presence of unresectable liver disease was also discussed in this module. Lastly, the approach to the unresectable disease was also discussed, focusing in the best chemotherapy regimens and hole of chemo-embolization.

Download Full-text

Localized Pancreatic Cancer: Multidisciplinary Management

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_160827 ◽

2016 ◽

pp. e217-e226 ◽

Cited By ~ 6

Author(s):

Andrew L. Coveler ◽

Joseph M. Herman ◽

Diane M. Simeone ◽

E. Gabriela Chiorean

Keyword(s):

Pancreatic Cancer ◽

Biomarker Discovery ◽

Locally Advanced ◽

Optimal Treatment ◽

Treatment Modalities ◽

Vascular Involvement ◽

Single Digit ◽

Borderline Resectable ◽

Unresectable Disease ◽

Tumor Boards

Pancreatic cancer is an aggressive cancer that continues to have single-digit 5-year mortality rates despite advancements in the field. Surgery remains the only curative treatment; however, most patients present with late-stage disease deemed unresectable, either due to extensive local vascular involvement or the presence of distant metastasis. Resection guidelines that include a borderline resectable group, as well as advancements in neoadjuvant chemotherapy and radiation that improve resectability of locally advanced disease, may improve outcomes for patients with more invasive disease. Multi-agent chemotherapy regimens fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) and nab-paclitaxel with gemcitabine improved response rates and survival in metastatic pancreatic cancer and are now being used in earlier stages for patients with localized potentially resectable and unresectable disease, with goals of downstaging tumors to allow margin-negative resection and reducing systemic recurrence. Chemoradiotherapy, although still controversial for both resectable and unresectable pancreatic cancer, is being used in the context of contemporary chemotherapy backbone regimens, and novel radiation techniques such as stereotactic body frame radiation therapy (SBRT) are studied on the premise of maintaining or improving efficacy and reducing treatment duration. Patient selection for optimal treatment designation is currently provided by multidisciplinary tumor boards, but biomarker discovery, in blood, tumors, or through novel imaging, is an area of intense research. Results to date suggest that some patients with unresectable disease at the outset have survival rates as good as those with initially resectable disease if able to undergo surgical resection. Long-term follow-up and improved clinical trials options are needed to determine optimal treatment modalities for patients with localized pancreatic cancer.

Download Full-text

Gastrointestinal neuroendocrine tumours. Management of unresectable disease and non-surgical treatment options

Hellenic Journal of Surgery ◽

10.1007/s13126-011-0004-7 ◽

2011 ◽

Vol 83 (1) ◽

pp. 21-28

Author(s):

A. Valatsou ◽

M. Tzanela

Keyword(s):

Surgical Treatment ◽

Neuroendocrine Tumours ◽

Treatment Options ◽

Unresectable Disease ◽

Gastrointestinal Neuroendocrine Tumours ◽

Non Surgical Treatment

Download Full-text

Malignant transformation of teratoma to primitive neuroectodermal tumor (PNET): Outcome analysis with retroperitoneal lymph node dissection and PNET specific chemotherapy

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.5081 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 5081-5081

Author(s):

R. Foster ◽

Y. Ehrlich ◽

T. M. Ulbright ◽

L. Cheng ◽

R. Bihrle ◽

...

Keyword(s):

Lymph Node ◽

Malignant Transformation ◽

Lymph Node Dissection ◽

Retroperitoneal Lymph Node Dissection ◽

Node Dissection ◽

Retroperitoneal Lymph Node ◽

Term Survival ◽

Long Term Survival ◽

Unresectable Disease

5081 Background: Malignant transformation of teratoma to PNET is a rare entity. Surgical resection has been the mainstay of therapy because these tumors are not curable with cisplatin based chemotherapy. We report long-term survival and potential cure with retroperitoneal lymph node dissection (RPLND) and PNET specific chemotherapy. Methods: Retrospective review of 75 patients (pts) with PNET in the testis or at distant metastasis treated from Jan 1988 to Dec 2007. 74 had RPLND as part of initial treatment or at relapse. PNET specific chemotherapy consisted of cyclophosphamide, doxorubicin, vincristine alternating with ifosfamide and etoposide. Available PNET specimens were tested for the Ewing's sarcoma (EWS) translocation using a FISH-based method. Results: The median follow-up was 40 months (range 2 to 235). 27 pts presented with clinical stage I disease. 18 underwent primary RPLND with PNET in the retroperitoneum in 5. 4 are dead of disease (DOD). 9 elected surveillance or adjuvant chemotherapy. 8 relapsed with PNET. 4 are DOD. 48 pts presented with metastatic disease. 20 are DOD, 24 have no evidence of disease (NED) and 4 are alive with disease. 50 of 75 pts had PNET documented metastasis with an estimated 5 years disease specific survival of 47%. 10 of these were treated with PNET specific chemotherapy for unresectable disease. 8 of the 10 achieved objective response with the duration of response ranging from 4 to 73 months. 2 pts are NED. 2 additional pts were treated with PNET specific chemotherapy as adjuvant to RPLND. Both are continuously NED. Specimens from 14 pts were tested for the EWS translocation, 2 were positive. Conclusions: Malignant transformation of teratoma to PNET carries an adverse prognosis. RPLND is an integral part of the therapeutic strategy. PNET specific chemotherapy, adjuvant to RPLND or for treatment of unresectable disease followed by surgery, may result in long-term survival and potential cure. No significant financial relationships to disclose.

Download Full-text

Did patients (pts) in OPTiM, a trial of unresectable melanoma, have truly unresectable disease?: Results from an independent review.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.e20109 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. e20109-e20109

Author(s):

Mark B. Faries ◽

Mark Shilkrut ◽

Eduard Gasal ◽

Vernon K. Sondak

Keyword(s):

Unresectable Disease ◽

Independent Review

Download Full-text

A phase II trial of escalated dose proton radiotherapy with elective nodal irradiation and concomitant chemotherapy for patients with unresectable, borderline resectable, or medically inoperable pancreatic adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.tps513 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. TPS513-TPS513

Author(s):

Romaine Charles Nichols ◽

Christopher G. Morris ◽

Bradford S. Hoppe ◽

Michael Scott Rutenberg

Keyword(s):

Disease Control ◽

Pancreatic Adenocarcinoma ◽

Median Survival ◽

Phase Ii ◽

Radiation Treatment ◽

Primary Objective ◽

Curative Surgery ◽

Borderline Resectable ◽

Unresectable Disease ◽

Gi Toxicity

TPS513 Background: The prognosis for patients with localized pancreatic adenocarcinoma who are not surgical candidates is poor. Median survival for patients with unresectable disease on the LAP-07 trial was between 15.2 and 16.4 months (Hammel P, et al. J Clin Oncol 31, 2013 [suppl; abstr LBA4003]). The absence of a survival advantage for x-ray based radiotherapy may be due to toxicity. Patients characterized as having “borderline resectable” disease fair somewhat better - although many are not converted to resectability with standard regimens. Intensified local/regional therapy for "initially unresectable" patients might 1.) Increase the share of patients undergoing curative surgery and 2.) Improve local disease control for patients who remain unresectable. A phase II study for patients with unresectable disease treated with proton therapy to a dose of 59.4 Gy (RBE) demonstrated an 18.4 month median survival without grade 2 or higher GI toxicity – suggesting the feasibility of dose intensification (Sachsman S, et al. Int J Particle Ther. 2014;1[3]:692–701.). The current protocol offers a 6% increase in radiotherapy dose with a 25% increase in dose per fraction with the goal of improving local control and extending survival. Methods: Eligibility: Biopsy proven adenocarcinoma of the pancreas that is unresectable, borderline resectable, or medically inoperable. No evidence of metastatic disease. Prior chemotherapy allowed. Treatment: 40.50 Gy (RBE) in 18 fractions to gross disease and an elective nodal volume followed by a 22.50 Gy (RBE) in 10 fraction boost to gross disease (total dose 63 Gy [RBE] in 28 fractions) with concomitant capecitabine (1,000 mg PO BID) on radiation treatment days. Surgery between 8 and 16 weeks of radiotherapy completion if radiographic studies suggest operability. Primary Objective: Improve 12 month survival from 50% to 75%. Secondary Objectives: Improve local and regional disease control Increase share of patients being converted to resectable. Compare GI toxicity with historical benchmarks. Assess quality of life. Sample Size:60 patients Clinical trial information: 02598349.

Download Full-text