Neoadjuvant chemotherapy does not improve survival for patients with high volume colorectal peritoneal metastases undergoing cytoreductive surgery.

BACKGROUND: Colorectal peritoneal metastases (CRPM) affects 15% of patients at initial colorectal cancer diagnosis. Neoadjuvant chemotherapy (NAC) prior to cytoreductive surgery (CRS) has been demonstrated to be a safe and feasible option, however there is limited data describing its efficacy in advanced peritoneal disease. This study evaluated the effect of NAC on survival in patients with high volume CRPM undergoing CRS with or without HIPEC. METHODS: A retrospective review of all patients who underwent CRS with or without HIPEC for CRPM from 2004 to 2019 at our institution was performed. The cohort was divided based on peritoneal carcinomatosis index (PCI) at surgery: Low Volume (PCI ≤ 16) and High Volume (PCI > 16). RESULTS: A total of 326 patients underwent CRS with HIPEC for CRPM. There were 39 patients (12%) with High Volume disease, and 15 of these (38%) received NAC. Patients with High Volume disease had significantly longer operating time, lower likelihood of complete macroscopic cytoreduction (CC-0 score), longer intensive care unit length of stay and longer hospital stay compared to Low Volume disease. In High Volume disease, the NAC group had a significantly shorter median survival of 14.4 months compared to 23.8 months in the non-NAC group (p = 0.046). CONCLUSION: Patients with High Volume CRPM achieved good median survival following CRS with HIPEC, which challenges the current PCI threshold for offering CRS. The use of NAC in this cohort did not increase perioperative morbidity but was associated with significantly shorter median survival compared to upfront surgery.

Potentially burdensome care at the end-of-life for cancer decedents: a retrospective population-wide study.

BACKGROUND: Variation persists in the quality of end-of-life-care (EOLC) for people with cancer. This study aims to describe the characteristics of, and examine factors associated with, indicators of potentially burdensome care provided in hospital, and use of hospital services in the last 12 months of life for people who had a death from cancer. METHOD: A population-based retrospective cohort study of people aged ≥ 20 years who died with a cancer-related cause of death during 2014-2019 in New South Wales, Australia using linked hospital, cancer registry and mortality records. Ten indicators of potentially burdensome care were examined. Multinominal logistic regression examined predictors of a composite measure of potentially burdensome care, consisting of > 1 ED presentation or > 1 hospital admission or ≥ 1 ICU admission within 30 days of death, or died in acute care. RESULTS: Of the 80,005 cancer-related deaths, 86.9% were hospitalised in the 12 months prior to death. Fifteen percent had > 1 ED presentation, 9.9% had > 1 hospital admission, 8.6% spent ≥ 14 days in hospital, 3.6% had ≥ 1 intensive care unit admission, and 1.2% received mechanical ventilation on ≥ 1 occasion in the last 30 days of life. Seventeen percent died in acute care. The potentially burdensome care composite measure identified 20.0% had 1 indicator, and 10.9% had ≥ 2 indicators of potentially burdensome care. Compared to having no indicators of potentially burdensome care, people who smoked, lived in rural areas, were most socially economically disadvantaged, and had their last admission in a private hospital were more likely to experience potentially burdensome care. Older people (≥ 55 years), females, people with 1 or ≥ 2 Charlson comorbidities, people with neurological cancers, and people who died in 2018-2019 were less likely to experience potentially burdensome care. Compared to people with head and neck cancer, people with all cancer types (except breast and neurological) were more likely to experience ≥ 2 indicators of potentially burdensome care versus none. CONCLUSION: This study shows the challenge of delivering health services at end-of-life. Opportunities to address potentially burdensome EOLC could involve taking a person-centric approach to integrate oncology and palliative care around individual needs and preferences.

Use of Prognostic Factors and Scores in Selection of Patients with Colorectal Cancer Peritoneal Metastasis (CRPM) for Cytoreductive Surgery and Intraperitoneal Chemotherapy (CRS/IPC): Results of an International Survey Among Oncologic Clinicians.

BACKGROUND: No universally accepted guidelines exist for treatment of patients with colorectal cancer peritoneal metastases (CRPM) undergoing cytoreductive surgery and intraperitoneal chemotherapy (CRS/IPC). Several uncertainties remain concerning almost every aspect of this treatment modality, resulting in marked variability in patient management and likely outcomes. This survey aimed to define variations and trends in clinician decision making more clearly. METHODS: A 41-question web-based survey was distributed electronically via the Peritoneal Surface Oncology Group International (PSOGI), the International Society for the Study of Pleura and Peritoneum (ISSPP) as well as via social media (particularly Twitter). The survey sought to address and record clinician responses regarding patient workup/assessment, selection for preoperative systemic therapy, preoperative and intraoperative selection for CRS/IPC, and consideration of prognosis and complications. RESULTS: Complete responses were received from 60 clinicians from 45 centres in 22 countries. Upon assessment of survey responses, several interesting trends were noted in each section of the survey. Significant variability in surgeon practice and opinion were identified concerning almost every aspect of the treatment modality. CONCLUSION: This international survey provides the most comprehensive insight into clinician decision-making trends regarding patient assessment, selection and management. This should allow areas of variability to be more clearly defined and could potentially prompt development of initiatives for achieving consensus and standardisation of care in the future.

External validation of prognostic scores and comparison of predictive accuracy for patients with colorectal cancer with peritoneal metastases considered for cytoreductive surgery and intraperitoneal chemotherapy.

BACKGROUND AND OBJECTIVES: Prognostic scores are developed to facilitate the selection of patients with colorectal cancer peritoneal metastases (CRPM) for treatment with cytoreductive surgery (CRS) ± intraperitoneal chemotherapy (IPC). Three prominent prognostic scores are the Peritoneal Surface Disease Severity Score (PSDSS), the Colorectal Peritoneal Metastases Prognostic Surgical Score (COMPASS), and the modified COloREctal-Pc (mCOREP). We externally validate these scores and compare their predictive accuracy. METHODS: Data from consecutive CRPM patients who underwent CRS/IPC from 1996 to 2018 was used to externally validate COMPASS, PSDSS, and mCOREP. Analysis evaluated the efficacy of each score in predicting (1) open-close laparotomy-those found at laparotomy to not be eligible for curative intent CRS/IPC, (2) surgical futility-those who underwent open-close laparotomy, palliative debulking surgery, or had an overall survival of less than 12 months, and (3) overall and recurrence-free survival (OS, RFS). RESULTS: Prognostic scores were calculated for the 174-patient external validation cohort. COMPASS was most accurate in predicting open-close laparotomy, futile surgery, and survival (OS and RFS). Area under the curve (AUC) for open-close prediction was 0.78 (95% confidence interval, CI: 0.68-0.87), representing useful discrimination. However, AUC for futility prediction was 0.62 (95% CI: 0.52-0.71), and C-statistic for OS was 0.65 indicating only possibly helpful discrimination. C-statistic for RFS was 0.59 indicating poor discrimination. CONCLUSION: While COMPASS showed the best statistical behavior, accuracy for several clinically relevant outcomes remains low, and thus applicability to clinical practice limited.

Exploring the practicality and acceptability a brief exercise communication and clinician referral pathway in cancer care: a feasibility study.

BACKGROUND: The majority of cancer patients and cancer care clinicians-CCCs (e.g., oncologists) believe that exercise is an important adjunct therapy that should be embedded in standard practice. Yet, CCCs do not routinely discuss exercise with their patients, nor do they regularly refer them to exercise professionals (e.g., exercise physiologists-EPs). This study evaluated the feasibility and acceptability of an evidence-based approach to improving exercise communication between CCCs and their patients, including an exercise referral pathway. METHODS: Implementation and testing of the Exercise Communication and Referral Pathway (ECRP) occurred in Sydney, Australia. The ECRP included a brief oncology-initiated communication exchange with patients, CCC exercise referral to an EP, followed by EP-initiated telephone consultation with patients concerning tailored exercise advice. Participant perceptions concerning the feasibility and applicability of the ECPR were evaluated. Semi-structured interviews were conducted with CCCs (n = 3), cancer patients (n = 21), and an EP (n = 1). Inductive thematic analysis was undertaken. RESULTS: Analysis generated three themes: (1) Navigating the role of CCCs in the ECRP, suggesting that oncology-initiated communication is a cue to action, however there was a lack of role clarity regarding exercise referral; (2) Implementing Patient-Orientated Care within a Standardised Pathway, highlighting the need for tailored information and advice for patients that reflects individual disease, socio-cultural, and environmental factors, and; (3) Taking Steps Towards Action, revealing the need for structural (e.g., EP initiated contact with patients) and policy changes (i.e., changes to Medicare, direct oncologist referral) to engage patients and better integrate exercise as part of standard care. CONCLUSIONS: Findings provide important insights into improving oncology-patient exercise communication and developing an exercise referral pathway to increase engagement and patient reach. However, individual (e.g., experience, knowledge) and contextual factors (e.g., time, resources) need consideration when implementing an ECRP. TRIAL REGISTRATION: This trial was prospectively registered with the Australian New Zealand Clinical (#ACTRN12620000358943) on March 13, 2020.

Evaluation of pharmacogenomics and hepatic nuclear imaging-related covariates by population pharmacokinetic models of irinotecan and its metabolites.

BACKGROUND: Body surface area (BSA)-based dosing of irinotecan (IR) does not account for its pharmacokinetic (PK) and pharmacodynamic (PD) variabilities. Functional hepatic nuclear imaging (HNI) and excretory/metabolic/PD pharmacogenomics have shown correlations with IR disposition and toxicity/efficacy. This study reports the development of a nonlinear mixed-effect population model to identify pharmacogenomic and HNI-related covariates that impact on IR disposition to support dosage optimization. METHODS: Patients had advanced colorectal cancer treated with IR combination therapy. Baseline blood was analysed by Affymetrix DMET™ Plus Array and, for PD, single nucleotide polymorphisms (SNPs) by Sanger sequencing. For HNI, patients underwent 99mTc-IDA hepatic imaging, and data was analysed for hepatic extraction/excretion parameters. Blood was taken for IR and metabolite (SN38, SN38G) analysis on day 1 cycle 1. Population modelling utilised NONMEM version 7.2.0, with structural PK models developed for each moiety. Covariates include patient demographics, HNI parameters and pharmacogenomic variants. RESULTS: Analysis included (i) PK data: 32 patients; (ii) pharmacogenomic data: 31 patients: 750 DMET and 22 PD variants; and (iii) HNI data: 32 patients. On initial analysis, overall five SNPs were identified as significant covariates for CLSN38. Only UGT1A3_c.31 T > C and ABCB1_c.3435C > T were included in the final model, whereby CLSN38 reduced from 76.8 to 55.1%. CONCLUSION: The identified UGT1A3_c.31 T > C and ABCB1_c.3435C > T variants, from wild type to homozygous, were included in the final model for SN38 clearance.

An exploratory survey study of disorder and its association with safety culture in four hospitals.

BACKGROUND: Signs of disorder in neighbourhoods (e.g., litter, graffiti) are thought to influence the behaviour of residents, potentially leading to violations of rules and petty criminal behaviour. Recently, these premises have been applied to the hospital context, with physical and social disorder found to have a negative association with patient safety. Building on these results, the present study investigates whether physical and social disorder differ between hospitals, and their relationship to safety culture. METHODS: We conducted a cross sectional survey with Likert-style and open response questions administered in four Australian hospitals. All staff were invited to participate in the pilot study from May to September 2018. An analysis of variance (ANOVA) was used to examine differences in disorder by hospital, and hierarchical linear regression assessed the relationship of physical and social disorder to key aspects of safety culture (safety climate, teamwork climate). Open responses were analysed using thematic analysis to elaborate on manifestations of hospital disorder. RESULTS: There were 415 survey respondents. Significant differences were found in perceptions of physical disorder across the four hospitals. There were no significant differences between hospitals in levels of social disorder. Social disorder had a significant negative relationship with safety and teamwork climate, and physical disorder significantly predicted a poorer teamwork climate. We identified five themes relevant to physical disorder and four for social disorder from participants' open responses; the preponderance of these themes across hospitals supported quantitative results. CONCLUSIONS: Findings indicate that physical and social disorder are important to consider in attempting to holistically understand a hospital's safety culture. Interventions that target aspects of physical and social disorder in a hospital may hold value in improving safety culture and patient safety.

The complexities, coordination, culture and capacities that characterise the delivery of oncology services in the common areas of ambulatory settings.

BACKGROUND: Relatively little is understood about real-world provision of oncology care in ambulatory outpatient clinics (OPCs). This study aimed to: 1) develop an understanding of behaviours and practices inherent in the delivery of cancer services in OPC common areas by characterising the organisation and implementation of this care; and 2) identify barriers to, and facilitators of, the delivery of this care in OPC common areas. METHODS: A purpose-designed ethnographic study was employed in four public hospital OPCs. Informal field scoping activities were followed by in-situ observations, key informant interviews and document review. A view of OPCs as complex adaptive systems was used as a scaffold for the data collection and interpretation, with the intent of understanding 'work as done'. Data were analysed using an adapted "Qualitative Rapid Appraisal, Rigorous Analysis" approach. RESULTS: Field observations were conducted over 135 h, interviews over 6.5 h and documents were reviewed. Analysis found six themes. Staff working in OPCs see themselves as part of small local teams and as part of a broader multidisciplinary care team. Professional role boundaries could be unclear in practice, as duties expanded to meet demand or to stop patients "falling through the cracks." Formal care processes in OPCs were supported by relationships, social capital and informal, but invaluable, institutional expertise. Features of the clinic layout, such as the proximity of departments, affected professional interactions. Staff were aware of inter- and intra-service communication difficulties and employed strategies to minimise negative impacts on patients. We found that complexity, coordination, culture and capacity underpin the themes that characterise this care provision. CONCLUSIONS: The study advances understanding of how multidisciplinary care is delivered in ambulatory settings and the factors which promote or inhibit effective care practice. Time pressures, communication challenges and competing priorities can pose barriers to care delivery. OPC care is facilitated by: self-organisation of participants; professional acumen; institutional knowledge; social ties and relationships between and within professional groups; and commitment to patient-centred care. An understanding of the realities of 'work-as-done' may help OPCs to sustain high-quality care in the face of escalating service demand.

"Time is of the essence": relationship between hospital staff perceptions of time, safety attitudes and staff wellbeing.

BACKGROUND: Hospitals are perceived as fast-paced and complex environments in which a missed or incorrect diagnosis or misread chart has the potential to lead to patient harm. However, to date, limited attention has been paid to studying how hospital sociotemporal norms may be associated with staff wellbeing or patient safety. The aim of this study was to use novel network analysis, in conjunction with well-established statistical methods, to investigate and untangle the complex interplay of relationships between hospital staff perceived sociotemporal structures, staff safety attitudes and work-related well-being. METHOD: Cross-sectional survey data of hospital staff (n = 314) was collected from four major hospitals in Australia. The survey included subscales from the Organizational Temporality Scale (OTS), two previously established scales of safety attitudes (teamwork climate and safety climate) and measures of staff-related wellbeing (job satisfaction, emotional exhaustion, depersonalisation). RESULTS: Using confirmatory factor analysis, we first tested a 19-item version of the OTS for use in future studies of hospital temporality (the OTS-H). Novel psychological network analysis techniques were then employed, which identified that "pace" (the tempo or rate of hospital activity) occupies the central position in understanding the complex relationship between temporality, safety attitudes and staff wellbeing. Using a path analysis approach, serial mediation further identified that pace has an indirect relationship with safety attitudes through wellbeing factors, that is, pace impacts on staff wellbeing, which in turn affects hospital safety attitudes. CONCLUSIONS: The findings of this study are important in revealing that staff wellbeing and safety attitudes can be significantly improved by placing more focus on temporal norms, and in particular hospital pace. There are implications for increasing levels of trust and providing staff with opportunities to exercise greater levels of control over their work.

What are the attitudes of health professionals regarding patient reported outcome measures (PROMs) in oncology practice? A mixed-method synthesis of the qualitative evidence.

BACKGROUND: The adoption of Patient Reported Outcome Measures (PROMs) in cancer care has been widely advocated, but little is known about the evidence for the implementation of PROMs in practice. Qualitative research captures the perspectives of health professionals as end-users of PROMs and can be used to inform adoption efforts. This paper presents a systematic review and synthesis of qualitative research conducted to address the question: What are the attitudes of health professionals towards PROMs in oncology, including any barriers and facilitators to the adoption of PROMS, reported in qualitative evidence? METHODS: Systematic searches of qualitative evidence were undertaken in four databases and reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies published in English between 1998 and 2018, which reported qualitative findings about the attitudes of health professionals working in oncology towards PROMs were eligible. Studies were assessed using the Critical Appraisal Skills Programme's Qualitative Research Checklist. A sentiment analysis was conducted on primary text to examine the polarity (neutral, positive or negative) of health professionals' views of PROMs. Qualitative meta-synthesis was conducted using a constant comparative analysis. RESULTS: From 1227 articles after duplicates were removed, with 1014 excluded against the screening criteria, 213 full text articles remained and were assessed; 34 studies met the inclusion criteria and were included. The majority of studies were of good quality. Sentiment analysis on primary text demonstrated an overall positive polarity from the expressed opinions of health professionals. The meta-synthesis showed health professionals' attitudes in four domains: identifying patient issues and needs using PROMs; managing and addressing patient issues; the care experience; and the integration of PROMs into clinical practice. CONCLUSIONS: From the accounts of health professionals, the fit of PROMs with existing practice, how PROMs are valued, capacity to respond to PROMs and the supports in place, formed the key factors which may impede or promote adoption of PROMs in routine practice. To assist policy-makers and services involved in implementing these initiatives, further evidence is required about the relationship between PROMs data collection and corresponding clinical actions. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42019119447, 6th March, 2019.

Assessing suitability for long-term colorectal cancer shared care: a scenario-based qualitative study.

BACKGROUND: Shared care is the preferred model for long-term survivorship care by cancer survivors, general practitioners and specialists. However, survivorship care remains specialist-led. A risk-stratified approach has been proposed to select suitable patients for long-term shared care after survivors have completed adjuvant cancer treatment. This study aims to use patient scenarios to explore views on patient suitability for long-term colorectal cancer shared care across the risk spectrum from survivors, general practitioners and specialists. METHODS: Participants completed a brief questionnaire assessing demographics and clinical issues before a semi-structured in-depth interview. The interviews focused on the participant's view on suitability for long term cancer shared care, challenges and facilitators in delivering it and resources that would be helpful. We conducted thematic analysis using an inductive approach to discover new concepts and themes. RESULTS: Interviews were conducted with 10 cancer survivors, 6 general practitioners and 9 cancer specialists. The main themes that emerged were patient-centredness, team resilience underlined by mutual trust and stronger system supports by way of cancer-specific training, survivorship care protocols, shared information systems, care coordination and navigational supports. CONCLUSIONS: Decisions on the appropriateness of this model for patients need to be made collaboratively with cancer survivors, considering their trust and relationship with their general practitioners and the support they need. Further research on improving mutual trust and operationalising support systems would assist in the integration of shared survivorship care.

Short- and Long-Term Outcomes of Patients Requiring Gastrectomy During Cytoreductive Surgery and Intraperitoneal Chemotherapy for Lower-Gastrointestinal Malignancies: A Propensity Score-Matched Analysis.

OBJECTIVES: This study was designed to assess the short- and long-term outcomes of gastric resection in cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) for lower gastrointestinal (GI) malignancies. METHODS: Patients with adenocarcinoma and appendiceal mucinous neoplasms were included. Redo and incomplete cytoreductions were excluded. A total of 756 patients were identified. Of these, 65 underwent gastric resection, 11 underwent wedge, 43 distal, and 11 subtotal and total gastrectomy. Preoperative differences were assessed for and addressed with matching. Perioperative outcomes, overall survival (OS), and risk-free survival (RFS) were assessed in two analyses: first all gastric resections were included and the second excluded wedge resections. Subgroup analysis according to diagnosis subtype was conducted. RESULTS: Demographic analysis revealed that markers of tumor aggression and poor nutrition were prevalent in the gastrectomy group. The matched analysis for gastric resections revealed higher rates of reoperation (38% vs. 22%, p = 0.028). After excluding wedge resections, increased rates of reoperation (40% vs. 22%, 0.019), grade 3/4 morbidity (76% vs. 59%, p = 0.036), and hospital stay (34 vs. 27 days, p = 0.012) were observed. For the unmatched cohort, OS (103 vs. 69 months, p = 0.501) and RFS (17 vs. 18 months, p = 0.181) for patients with CC = 0 were insignificantly different. In comparison for CC > 0, OS (31 vs. 83 months, p < 0.001) and RFS (9 vs. 20 months, p < 0.001) were significantly reduced in gastric resection. For the matched cohort, after excluding wedges, gastrectomy did not significantly decrease OS. However, RFS was decreased (11 vs. 20 months, p = 0.016). CONCLUSIONS: Despite high postoperative morbidity, when complete cytoreduction is achieved, the need for gastric resection is not associated with inferior long-term outcomes.

Preoperative Nutrition Status and Postoperative Outcomes in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a complex surgery to treat peritoneal surface malignancy (PSM). PSM and gastrointestinal (GI) resection from CRS can lead to significant GI symptoms and malnutrition. There is limited research into the nutrition status of this patient group and the impact of malnutrition on morbidity. OBJECTIVE: This study aims to determine if preoperative malnutrition, assessed using the Subjective Global Assessment (SGA), is associated with postoperative morbidity and increased length of stay (LOS) in patients undergoing CRS/HIPEC for PSM. METHODS: This study prospectively assessed the nutritional status of patients undergoing CRS/HIPEC using a validated nutrition assessment tool. Preoperative clinical symptoms, Peritoneal Cancer Index (PCI), intraoperative blood transfusions, operative time, GI resections, postoperative morbidity, and LOS, as well as pre- and postoperative nutritional interventions, were recorded. The impact of preoperative nutritional status was assessed in relation to postoperative complications and hospital LOS. RESULTS: The study included 102 participants; 34 patients (33%) were classified as malnourished (SGA = B or C). Preoperative weight loss (15% vs. 74%; p ≤ 0.001) and the presence of clinical symptoms (18% vs. 47%; p = 0.002) were significantly higher in malnourished patients. While PCI, intraoperative blood transfusions, and GI resections were independent predictors of morbidity, malnutrition was significantly associated with infectious complications and LOS. For each grade of worsening malnutrition, LOS increased by an average of 7.65 days. CONCLUSIONS: Preoperative malnutrition is prevalent in patients undergoing CRS/HIPEC and postoperative morbidity is common. Malnutrition is linked to LOS and plays a role in postoperative outcomes such as infection. Clear pre- and postoperative nutrition pathways are needed to optimize nutrition support and postoperative recovery.

Long-term survival outcomes of cytoreductive surgery and perioperative intraperitoneal chemotherapy: Single-institutional experience with 1225 cases.

BACKGROUND AND OBJECTIVES: To review long-term survival outcomes of patients with Peritoneal metastasis (PM) who underwent colorectal cancer (CRS) and intraperitoneal chemotherapy (PIC). METHODS: Patients that underwent CRS, with or without PIC, from January 1996 to March 2018 at the Peritonectomy Unit of St. George Hospital, Sydney were retrospectively analyzed from a prospectively maintained database. RESULTS: The study comprised of 1225 cases, including 687 females (56.1%) and 538 males (43.9%). Diagnoses included CRC (n = 363), followed by HAMN (n = 317), LAMN (n = 297), mesothelioma (n = 101), ovarian cancer (n = 55), and others including gastric, sarcoma, and neuroendocrine tumor (n = 92). The median OS, 5- and 10-year survivals for CRC were 35 months, 33% and 8%, respectively. Patients with LAMN, in relative to HAMN, experienced a higher median OS, 5- and 10-year survivals (248 months vs 63 months; 82% vs 52% and 59% vs 28%). The median OS for mesothelioma was 60 months with 5- and 10-year survivals of 48% and 19%, respectively. In ovarian cancer, the median OS was 30 months with 5- and 10-year survivals of 26% and 10%, respectively. For the remaining histological diagnoses, median OS and 5-year survival were 28 months and 27%, respectively. CONCLUSION: Our large-cohort data showed that CRS/PIC can provide long-term survival benefit to patients with PM of gastrointestinal and ovarian origin.

Iterative cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A multi-institutional experience.

BACKGROUND AND OBJECTIVES: The aims of this multi-institutional study were to assess the feasibility of iterative cytoreductive surgery (iCRS)/hyperthermic intraperitoneal chemotherapy, iCRS in colorectal peritoneal carcinomatosis (CRPC), evaluate survival, recurrence, morbidity and mortality outcomes, and identify prognostic factors for overall survival. METHODS: Patients with CRPC that underwent an iCRS, with or without intraperitoneal chemotherapy, from June 1993 to July 2016 at 13 institutions were retrospectively analyzed from prospectively maintained databases. RESULTS: The study comprised of 231 patients, including 126 females (54.5%) with a mean age at iCRS of 51.3 years. The iterative high-grade (3/4) morbidity and mortality rates were 23.4% and 1.7%, respectively. The median recurrence-free survival was 15.0 and 10.1 months after initial and iCRS, respectively. The median and 5-year survivals were 49.1 months and 43% and 26.4 months and 26% from the initial and iCRS, respectively. Independent negative predictors of survival from the initial CRS included peritoneal carcinomatosis index (PCI) > 20 ( P = 0.02) and lymph node positivity ( P = 0.04), and from iCRS, PCI > 10 ( P = 0.03 for PCI 11-20; P < 0.001 for PCI > 20), high-grade complications ( P = 0.012), and incomplete cytoreduction ( P < 0.001). CONCLUSION: iCRS can provide long-term survival benefits to highly selected colorectal peritoneal carcinomatosis patients with comparable mortality and morbidity rates to the initial CRS procedure. Careful patient selection is necessary to improve overall outcomes.

CEA to peritoneal carcinomatosis index (PCI) ratio is prognostic in patients with colorectal cancer peritoneal carcinomatosis undergoing cytoreduction surgery and intraperitoneal chemotherapy: A retrospective cohort study.

BACKGROUND AND OBJECTIVES: Serum tumor markers are prognostic in patients with colorectal cancer peritoneal carcinomatosis (CRPC) undergoing cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC). Assessment of the ratio of tumor marker to volume, as depicted by peritoneal carcinomatosis index (PCI), and how this may affect overall (OS) and recurrence free survival (RFS) has not been reported. METHODS: Survival effect of this ratio was analyzed in patients with CRPC managed from 1996 to 2016 with CRS and IPC. RESULTS: Of 260 patients included, those with low CEA/PCI ratio (<2.3) had longer median OS (56 vs 24 months, P = 0.001) and RFS (13 vs 9 months, P = 0.02). The prognostic impact of CEA/PCI ratio was most pronounced in patients with PCI ≤ 10 (OS of 72 vs 30 months, P < 0.001; RFS of 21 vs 10 months, P = 0.002). In multivariable analysis, elevated CEA/PCI ratio was independently associated with poorer OS (adjusted HR 1.85, 95%CI 1.11-3.10, P = 0.02) and RFS (adjusted HR 1.58, 95%CI 1.04-2.41, P = 0.03). CONCLUSION: CEA/PCI ratio is an independent prognostic factor for OS and RFS in CRPC. This novel approach allows both tumor activity and volume to be accounted for in one index, thus potentially providing a more accurate indication of tumor biological behavior.

Ovarian Cancer Surgery in Australia and New Zealand: A Survey to Determine Changes in Surgical Practice Over 10 Years.

OBJECTIVE: This study aimed to survey all practicing certified gynecological oncologists (CGOs) in Australia and New Zealand to determine their current surgical practice for primary advanced epithelial ovarian cancer (EOC) and compare the findings with an identical survey conducted 10 years previously. METHODS/MATERIALS: A questionnaire was e-mailed to all 53 practicing CGOs in Australia and New Zealand in July 2017 assessing their definition of optimal debulking for EOC, their use of neoadjuvant chemotherapy, and the surgical procedures they use to achieve cytoreduction. Results were compared with an identical study performed in 2007 using χ and logistic regression analysis. RESULTS: Response rate was 89% (47/53). A higher percentage of patients received neoadjuvant chemotherapy before surgery in 2017 than in 2007 (43% vs 16%, respectively). In 2017, CGOs were more likely to define optimal debulking as zero residual disease (R0; 21/44 [48%] vs 6/34 [18%], P < 0.001). To achieve this, CGOs were significantly more likely to independently perform stripping/resection of the diaphragm (44/47 [94%] vs 15/34 [44%], P < 0.001) and, with assistance from surgical colleagues, perform resection of upper para-aortic lymph nodes (39/46 [85%] vs 21/34 [62%], P = 0.02) and parenchymal liver metastases (30/46 [65%] vs 13/34 [38%], P = 0.02). They were now less likely to resect/reimplant the ureter without assistance (23% vs 53%, P = 0.01). A surgeon's definition of optimal debulking as R0 was significantly associated with a high use of neoadjuvant chemotherapy (in ≥50% of patients). CONCLUSIONS: Certified gynecological oncologists' definition of optimal debulking for primary EOC is more likely to be R0 in 2017 than in 2007. Radical abdominal surgery was performed more often in 2017, requiring assistance by a surgical colleague in many cases. An increased use of neoadjuvant chemotherapy was the only factor significantly associated with CGOs' definition of optimal debulking as R0.

Survival difference between mucinous vs. non-mucinous colorectal cancer following cytoreductive surgery and intraperitoneal chemotherapy.

BACKGROUND: It is believed that the oncologic behavior of mucinous colorectal adenocarcinoma (MC) is different from non-mucinous adenocarcinoma (NMC). The aim of the study is to compare long-term survivals between patients with MC and those with NMC following cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC). METHODS: This was a retrospective study of prospectively collected data of patients with peritoneal metastases of colorectal origin following CRS and IPC. Group I included patients with MC which was defined as being composed of >50% extracellular mucin. Group II included those with NMC. Subgroup analysis was performed according to the location of primary tumor. RESULTS: A total of 213 patients were included in this study. The two groups had similar hospital mortality, high dependency unit stay. MC group had a significantly longer mean intensive care unit (ICU) stay (p = .037) and total hospital stay (p = .037). There was no significant difference in overall survival (OS) and disease-free survival (DFS) between two groups (p = .657 and p = .938, respectively). Multivariate analysis showed that the presence of mucin was not an independent negative prognostic factor for OS (p = .190). CONCLUSION: In summary, patients with MC had a similar long-term survival outcome with those with NMC following CRS and IPC.

Early Postoperative Intraperitoneal Chemotherapy for Low-Grade Appendiceal Mucinous Neoplasms with Pseudomyxoma Peritonei: Is it Beneficial?

BACKGROUND: There is little evidence for the use of early postoperative intraperitoneal chemotherapy (EPIC) in patients with low-grade appendiceal mucinous neoplasms (LAMNs) with pseudomyxoma peritonei (PMP). This study aims to assess the outcomes regarding the use of EPIC in a large cohort of patients with LAMNs with PMP uniformly treated by cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC), all of whom received hyperthermic intraperitoneal chemotherapy (HIPEC), and most of whom also received EPIC. METHODS: This was a retrospective study of prospectively collected data of consecutive patients with peritoneal carcinomatosis of appendiceal origin who underwent CRS and PIC by one surgical team at St George Hospital in Sydney, Australia, between January 1996 and November 2015. Subgroup analyses were performed for patients with a high Peritoneal Cancer Index (PCI) >20 and also based on histopathological subtypes of LAMNs. RESULTS: A total of 250 patients formed the cohort of this study. No significant differences were observed in terms of hospital mortality (p = 0.153), major morbidity rate (i.e., grade III/IV; p = 0.593), intensive care unit stay (p = 0.764), and total hospital stay (p = 0.927); however, patients who received HIPEC + EPIC had a significantly longer stay in the high dependency unit. Multivariate analysis showed combined HIPEC with EPIC is an independent prognostic factor for better survival outcomes (hazard ratio 0.30, 95 % confidence interval 0.12-0.74; p = 0.009), adjusted for age, PCI, and histopathological subtypes. CONCLUSIONS: The combination of HIPEC + EPIC can provide additional survival benefits for patients with LAMNs with PMP compared with HIPEC alone, without increasing postoperative morbidity and mortality. EPIC should be considered following CRS and HIPEC for patients with LAMNs with PMP.