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Prophylactic HIPEC for Colorectal Cancers at High Risk of Developing Peritoneal Metastases

ABSTRACT: The study investigators hypothesize that prophylactic HIPEC is feasible and well tolerated in patients with colorectal cancers with high-risk of developing peritoneal recurrence. The aim of the pilot study is to test the feasibility of performing prophylactic HIPEC for colorectal cancer patients at high-risk of developing peritoneal recurrence in our institution, and determine the morbidity associated with such a procedure. Patients with high-risk of developing peritoneal recurrence are defined as patients with 1. tumours involving the serosa and adjacent viscera (i.e. T4 cancers) 2. krukenburg tumours (i.e. ovarian metastases) 3. perforated tumours 4. positive peritoneal fluid cytology 5. minimal synchronous PC (nodules <1cm in the omentum and/or close to the primary tumour). The study investigators plan to assess feasibility according to 1. The number of patients completing the treatment 2. Time to adjuvant systemic chemotherapy, to evaluate if there is delay to adjuvant treatment Morbidity will be measured according to the Clavien-Dindo Classification, and graded according to low versus high grade morbidity. If prophylactic HIPEC is shown to be feasible, with acceptable morbidity, the investigators aim to carry out a randomized controlled trial to determine the effectiveness of prophylactic HIPEC in preventing the development of peritoneal metastases in patients with colorectal cancer at high risk of peritoneal recurrence.

DISEASE(S): Neoplasm Metastasis,Colorectal Cancer,Colorectal Neoplasms,Peritoneal Metastases

PROVIDER: 2265047 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:This is the proteomics part of the above project. Purpose: No blood-based biomarkers to detect OPSCC early before symptoms develop or before clinically visible. Diagnosis is solely based on histology of a visible tumour. Most OPSCC patients are diagnosed at an advanced stage, which leads to significant morbidity and poor survival. If high-risk patients were identified with blood-based biomarkers before clear clinical manifestations, tumours could be detected and treated at an earlier stage. Causes of OPSCC include smoking, alcohol misuse, and human papillomavirus (HPV). Tumours are separated according to WHO recommendations into HPV+ OPSCC and HPV- OPSCC using the proxy histological marker p16. We additionally separated our patients into these groups to determine whether the serum glycopeptides would differ between HPV+ and HPV- tumours, as these are distinct clinical entities. Patients and Methods: Pre-treatment sera from 74 patients with OPSCC (including 26 p16- tumours and 48 p16+ tumours) and 12 controls were used, collected between the years 2012 and 2015 at the Department of Otorhinolaryngology – Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland. Samples were grouped as follows: early stage p16+ OPSCC (stage I only), early stage p16- OPSCC (stage I-II), p16+ (any stage), p16- (any stage), controls. In-parallel quantitative bulk serum proteomics and serum glycopeptidomics were performed. Results: We identified 78 bulk proteins in the serum, of which 33 significantly differed between early-stage p16- OPSCC and controls, 22 between early-stage p16+ OPSCC and controls, 1 between early-stage p16+ and early-stage p16- OPSCCs, and 30 between all p16+ and p16- OPSCCs. We identified glycopeptides from proteins including but not limited to alpha-1-antitrypsin, haptoglobin, and Immunoglobulin heavy constant alpha 1, and compared these with the protein expression levels in each comparison. Conclusions: We have identified novel serum glycopeptide biomarkers detect early-stage OPSCCs, to be evaluated further as a diagnostic panel to detect preclinical OPSCC in at-risk patients.

Project description:This is the glycopeptide part of the above project. Purpose: No blood-based biomarkers to detect OPSCC early before symptoms develop or before clinically visible. Diagnosis is solely based on histology of a visible tumour. Most OPSCC patients are diagnosed at an advanced stage, which leads to significant morbidity and poor survival. If high-risk patients were identified with blood-based biomarkers before clear clinical manifestations, tumours could be detected and treated at an earlier stage. Causes of OPSCC include smoking, alcohol misuse, and human papillomavirus (HPV). Tumours are separated according to WHO recommendations into HPV+ OPSCC and HPV- OPSCC using the proxy histological marker p16. We additionally separated our patients into these groups to determine whether the serum glycopeptides would differ between HPV+ and HPV- tumours, as these are distinct clinical entities. Patients and Methods: Pre-treatment sera from 74 patients with OPSCC (including 26 p16- tumours and 48 p16+ tumours) and 12 controls were used, collected between the years 2012 and 2015 at the Department of Otorhinolaryngology – Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland. Samples were grouped as follows: early stage p16+ OPSCC (stage I only), early stage p16- OPSCC (stage I-II), p16+ (any stage), p16- (any stage), controls. In-parallel quantitative bulk serum proteomics and serum glycopeptidomics were performed. Results: We identified 78 bulk proteins in the serum, of which 33 significantly differed between early-stage p16- OPSCC and controls, 22 between early-stage p16+ OPSCC and controls, 1 between early-stage p16+ and early-stage p16- OPSCCs, and 30 between all p16+ and p16- OPSCCs. We identified glycopeptides from proteins including but not limited to alpha-1-antitrypsin, haptoglobin, and Immunoglobulin heavy constant alpha 1, and compared these with the protein expression levels in each comparison. Conclusions: We have identified novel serum glycopeptide biomarkers detect early-stage OPSCCs, to be evaluated further as a diagnostic panel to detect preclinical OPSCC in at-risk patients.

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Prophylactic HIPEC for Colorectal Cancers at High Risk of Developing Peritoneal Metastases

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