ABSTRACT
BACKGROUND: Ovarian carcinosarcoma (OCS) is an uncommon and aggressive malignancy, with poor response to current treatment approaches and no clear guidelines. Our aim is to evaluate the outcomes of an OCS cohort after cytoreduction with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). METHODS: A descriptive cohort study was performed. Patients who underwent CRS/HIPEC for peritoneal dissemination from tubo-ovarian malignancies (1999-2021) were retrospectively reviewed. Patients with confirmed histopathologic diagnosis of FIGO stage III/IV OCS were included. Overall (OS) and progression-free survival (PFS) were determined with the Kaplan-Meier method. RESULTS: Of 267 patients with tubo-ovarian malignancies reviewed, 7.5% (20/267) had OCS. Of these, 16 underwent CRS/HIPEC, including 9 for a new diagnosis and 7 for disease recurrence. Median age at surgery was 66.5 (IQR: 54.5-74.5) years. Nine (56.2%) patients were FIGO stage IV. Median peritoneal cancer index was 22 (IQR: 14-28). Complete cytoreduction was achieved in 15/16 (93.7%) cases. HIPEC agents included carboplatin (n = 7), cisplatin+doxorubicin (n = 4), and melphalan (n = 5). Major complications occurred in 4/16 (25%), with no 90-day mortality. Median follow-up was 41.8 months. Median PFS was 11.7 (95%CI: 10.5-17.1) months. Malignant bowel obstruction occurred in 3/16 (18.7%). Median OS from CRS/HIPEC was 21.3 (95%CI: 16.3-31.6) months, not reached for newly diagnosed vs 19.7 months for recurrent patients (p = 0.23). CONCLUSIONS: CRS/HIPEC showed promising survival and abdominal disease control with low rates of malignant obstruction in patients with advanced stage OCS. Collaborative studies with larger cohorts and longer follow-up may further elucidate the role of CRS/HIPEC in OCS.
Subject(s)
Carcinosarcoma , Hyperthermia, Induced , Ovarian Neoplasms , Peritoneal Neoplasms , Female , Humans , Middle Aged , Aged , Hyperthermic Intraperitoneal Chemotherapy , Cytoreduction Surgical Procedures/methods , Cohort Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Retrospective Studies , Peritoneal Neoplasms/drug therapy , Hyperthermia, Induced/methods , Neoplasm Recurrence, Local/pathology , Ovarian Neoplasms/pathology , Carcinosarcoma/therapy , Survival Rate , Combined Modality TherapyABSTRACT
INTRODUCTION: There are no available data on the efficacy of adjuvant chemotherapy (ACT) in stage IVA/B high-grade mucinous appendiceal cancer treated with CRS/HIPEC. We evaluated the association between ACT and survival in this cohort. MATERIALS AND METHODS: A single-institution retrospective cohort study using a prospective database was conducted. Stage IVA/B high-grade mucinous appendiceal cancer patients who underwent CRS/HIPEC with CC-0/1 were included. Survival was compared between ACT and no chemotherapy (NoCT) patients. Subgroup analysis was performed with adjustment for confounding variables. RESULTS: We identified 180 patients: 77 ACT and 103 NoCT. ACT regimens included 5-FU/capecitabine (13%), oxaliplatin-based (63%), and irinotecan-based (21%), combined with bevacizumab in 27% of cases. Median number of cycles was 9 (IQR: 6-12). Median overall survival (OS) did not significantly differ between ACT and NoCT (53 vs 75 months, p = 0.566). Multivariable Cox regression showed no OS benefit for ACT vs NoCT in patients with neoadjuvant chemotherapy (HR 1.14; 95%CI: 0.38-3.39) or without it (HR 1.33; 95%CI: 0.69-2.57), with signet ring cell (HR 0.89; 95%CI: 0.38-2.06) or other histologies (HR 1.11; 95%CI: 0.50-2.46), positive lymph nodes (HR 1.60; 95%CI: 0.74-3.49), or peritoneal cancer index ≥20 (HR 1.08; 95%CI: 0.55-2.11) after adjusting for other factors. CONCLUSIONS: In our cohort, colon-type ACT was not associated with better OS in stage IVA/B mucinous appendiceal cancer after CRS/HIPEC, even after adjusting for confounders. This may be due to different tumor biology than colon cancer or small sample size. Prospective collaborative studies are needed.
Subject(s)
Adenocarcinoma, Mucinous , Appendiceal Neoplasms , Hyperthermia, Induced , Peritoneal Neoplasms , Humans , Appendiceal Neoplasms/pathology , Hyperthermic Intraperitoneal Chemotherapy , Cytoreduction Surgical Procedures , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Retrospective Studies , Peritoneal Neoplasms/drug therapy , Adenocarcinoma, Mucinous/pathology , Chemotherapy, Adjuvant , Survival Rate , Combined Modality TherapyABSTRACT
BACKGROUND: Surgeons may hesitate to perform nephrectomy (NE) during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) due to a potential increase in morbidity. However, no data are available regarding the impact of NE on outcomes, so the authors decided to assess its safety during CRS/HIPEC. METHODS: A single-center propensity score-matched study was conducted using a prospective database (1994-2021). The study included patients who underwent NE during CRS/HIPEC with completeness of cytoreduction (CC) of 0, 1, or 2. Control subjects (no-NE) were selected in a 1:3 ratio using propensity score-matching weighted by age, histology, peritoneal cancer index (PCI), CC-0 or CC-1 rate, and length of surgery. RESULTS: Among 828 patients, 13 NE and 39 no-NE control subjects were identified. The indications for NE included tumor involvement of the ureter, hilum, and/or kidney with preserved (n = 8), decreased (n = 2), or absent (n = 3) function. NE patients received more intraoperative intravenous (IV) fluids (16,000 vs 11,500 mL; p = 0.045) and had a greater urine output (3200 vs 1913 mL; p = 0.008). NE patients received mitomycin C (40 mg for 90 min) or melphalan (50 mg/m2 for 90 min) without reduction of dose or time. Major morbidity (p = 0.435) and mortality (p = 1.000) were comparable between the two groups. No postoperative acute kidney injury was seen in either group. Adjuvant chemotherapy was administered to 46.2% of the NE and 35.9% of the no-NE patients (p = 0.553), with similar starting times (p = 0.903) between the groups. CONCLUSIONS: Nephrectomy performed during CRS/HIPEC does not seem to increase postoperative morbidity or to delay adjuvant chemotherapy, and NE can be performed if required for complete cytoreduction. The NE patients in our cohort did not have a reduction of mitomycin C or melphalan dose or perfusion time.
Subject(s)
Hyperthermia, Induced , Peritoneal Neoplasms , Humans , Hyperthermic Intraperitoneal Chemotherapy , Mitomycin , Combined Modality Therapy , Melphalan , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Peritoneal Neoplasms/therapy , Propensity Score , Retrospective Studies , Nephrectomy/adverse effects , Cytoreduction Surgical Procedures/adverse effects , Survival RateABSTRACT
BACKGROUND: The best management of patients who have unresectable mucinous appendiceal cancer (MAC) with peritoneal spread after a failed attempt at cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is unclear. This study aimed to assess outcomes after systemic chemotherapy (SCT) for patients with unresectable peritoneal metastases from high-grade MAC. METHODS: A single-center retrospective cohort study was conducted using a prospective CRS/HIPEC database. The study included high-grade MAC patients with peritoneal carcinomatosis who were deemed surgical candidates, but had an aborted CRS/HIPEC or only palliative HIPEC due to unresectable disease. Overall survival (OS) was compared. RESULTS: Of 72 identified patients, 20 received SCT and 52 did not (NoCT). The groups were balanced by age (p = 0.299), sex (p = 0.930), histopathologic subtype (p = 0.096), preoperative chemotherapy (p = 0.981), and postoperative major complication rates (p = 0.338). Both groups had extensive disease (median peritoneal cancer index at exploration, 39 vs 39). The median number of cycles was 12 (interquartile range [IQR], 6-15), and the median time between the procedure and SCT was 7 weeks (IQR, 5-10 weeks). The median follow-up period was 65 months. The median OS was significantly higher for the SCT group (26 months; 95 % confidence interval [CI], 10.8-41.5 months) than for the NoCT group (12 months; 95 % CI, 9.6-14.4 months) (p < 0.001), with hazard ratio (HR) of 0.22 (95 % CI, 0.08-0.66; p = 0.007) after adjustment for other factors. CONCLUSION: Systemic chemotherapy is associated with improved OS for high-grade MAC patients with unresectable peritoneal metastases who are deemed surgical candidates but underwent an unsuccessful CRS/HIPEC attempt. Further prospective studies with a larger sample are required to identify patient subgroups who benefit the most from SCT.
Subject(s)
Appendiceal Neoplasms , Hyperthermia, Induced , Peritoneal Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Appendiceal Neoplasms/pathology , Cytoreduction Surgical Procedures , Humans , Hyperthermic Intraperitoneal Chemotherapy , Peritoneal Neoplasms/secondary , Prospective Studies , Retrospective StudiesABSTRACT
BACKGROUND: Recurrence after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for appendiceal tumors (AT) with mucinous carcinomatosis peritonei (MCP) is common. The evidence favoring iterative procedures (iCRS/HIPEC) is limited, and its benefit is not clear for all patients. METHODS: Retrospective (1998-2020) cohorts of AT patients with MCP recurrence after the first CRS/HIPEC were analyzed. Outcomes were compared within tumor grades between iCRS/HIPEC patients and matched control patients without iCRS/HIPEC using propensity score matching (1:1). Post-recurrence survival (PRS) was measured from the date of recurrence after the first CRS/HIPEC to death or last contact. RESULTS: Overall, 55 iCRS/HIPEC patients were identified: 36 low-grade (LGMCP) patients, 13 high-grade (HGMCP) patients, and 6 HGMCP patients with signet-ring features (HGMCP-S). Nine patients had a third CRS/HIPEC. The median peritoneal cancer index (PCI) scores were 33, 19 and 10, with CC-0/1 achieved for 94.4%, 78.2% and 88.9% of the patients after the first, second, and third CRS/HIPEC, respectively. No 90-day postoperative mortality occurred. The median progression-free survival from the first CRS/HIPEC was 19.7 months for the iCRS/HIPEC patients versus 14.2 months for the matched control patients (p = 0.43). The median PRS was 80.2 months for iCRS/HIPEC versus 36.2 for the control patients (p < 0.001). For the iCRS/HIPEC versus the matched control patients, the median PRS by tumor grade was 174.1 versus 51.9 (p < 0.001) for the LGMCP, 42.0 versus 12.4 (p = 0.02) for the HGMCP, and 15.4 versus 8.1 months (p = 0.61) for the HGMCP-S patients, respectively. CONCLUSIONS: Selected low- and high-grade appendiceal cancer patients with MCP recurrence able to undergo iterative CRS/HIPEC procedures showed favorable outcomes and such patients should be considered for surgery when feasible. This survival benefit with iCRS/HIPEC is not evidenced in recurrent MCP with signet ring cell morphology.
Subject(s)
Adenocarcinoma, Mucinous , Adenocarcinoma , Appendiceal Neoplasms , Appendix , Hyperthermia, Induced , Peritoneal Neoplasms , Adenocarcinoma/pathology , Adenocarcinoma, Mucinous/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Appendiceal Neoplasms/pathology , Appendix/pathology , Combined Modality Therapy , Cytoreduction Surgical Procedures , Humans , Hyperthermic Intraperitoneal Chemotherapy , Neoplasm Recurrence, Local/pathology , Peritoneal Neoplasms/pathology , Retrospective Studies , Survival RateABSTRACT
BACKGROUND: Diaphragmatic resection (DR) is often required during cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) to achieve complete cytoreduction (CC). While CC provides the best survival, requiring a DR may indicate unfavorable tumor biology. We assessed how DR during CRS/HIPEC affects outcomes. METHODS: A retrospective cohort study was conducted using a prospective single-center database from October 1994-May 2020. Peritoneal surface malignancy patients who underwent CRS/HIPEC with CC-0/1/2 were assigned to DR and NoDR groups. Survival was measured using the Kaplan-Meier method. Subgroup analysis was performed for patients with peritoneal cancer index (PCI) ≥ 20 to eliminate confounding of more extensive disease in DR. RESULTS: Of 824 CRS/HIPECs, 774 were included: 134 DR and 640 NoDR. PCI was significantly higher in DR: 29 versus 21, p < 0.001. CC-0/1 rate was 89% in DR and 95% in NoDR (p = 0.003). Neither 100-day morbidity nor mortality differed between the groups (p = 0.355 and p = 1.000). Median follow-up was 64 months. Median overall survival (OS) was significantly lower in DR (32 vs. 96 months, p < 0.001). Subgroup analysis by tumor type in patients with PCI ≥ 20 showed significantly shorter OS in DR than NoDR in appendiceal (40 vs. 196 months, p < 0.001) and colorectal (14 vs. 23 months, p = 0.003), but not in ovarian tumors (32 vs. 42 months, p = 0.893), whereas median PCI did not differ among subgroups. CONCLUSIONS: DR during CRS/HIPEC does not increase morbidity and mortality. It is associated with worse survival in appendiceal and colorectal tumors, even after adjusting for tumor burden but does not appear to impact ovarian cancer survival.
Subject(s)
Appendiceal Neoplasms , Hyperthermia, Induced , Peritoneal Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Appendiceal Neoplasms/therapy , Combined Modality Therapy , Cytoreduction Surgical Procedures , Follow-Up Studies , Humans , Hyperthermic Intraperitoneal Chemotherapy , Peritoneal Neoplasms/drug therapy , Prospective Studies , Retrospective Studies , Survival RateABSTRACT
BACKGROUND: Peritoneal surface malignancies (PSM) can disseminate into the pleural cavity, increasing morbidity and mortality. While cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) improves outcomes for PSM with intra-abdominal spread, the optimal approach for patients with pleural dissemination from PSM remains unclear. It seems reasonable to apply peritoneal carcinomatosis management principles to patients with pleural lesions using CRS and hyperthermic intrathoracic chemotherapy (HITHOC). METHODS: We conducted a descriptive study to evaluate outcomes of PSM patients who underwent CRS/HITHOC for pleural dissemination using a high-volume PSM center's prospective database from October 1994-June 2020. CRS/HITHOC was performed via either diaphragmatic window during CRS/HIPEC (CRS/HIPEC+HITHOC) or thoracotomy as a separate procedure (CRS/HITHOC). RESULTS: Of 852 completed CRS/HIPECs, 18 HITHOCs in 15 patients were identified: 10 CRS/HIPEC+HITHOCs, and 8 CRS/HITHOCs. CRS/HIPEC+HITHOC primary tumors included: 4 appendix, 4 ovary, 1 colon, and 1 unknown. All (n = 8) CRS/HITHOC patients had recurrent appendiceal neoplasms. Complete cytoreduction was achieved in 90% of CRS/HIPEC+HITHOCs and 75% of CRS/HITHOCs. Major complications occurred in 20% of CRS/HIPEC+HITHOCs and 13% of CRS/HITHOCs with no 30-day mortality in either group. After median follow-up of 22 months, overall survival at 1, 3, and 5 years was 93.3%, 67.9%, and 67.9%, while 1-, 3-, and 5-year progression-free survival was 70.9%, 20.3%, and 20.3%. Intrapleural recurrence occurred in 1 CRS/HIPEC+HITHOC and 2 CRS/HITHOC patients. CONCLUSIONS: CRS/HITHOC performed via diaphragm or thoracotomy at high-volume centers is a safe option for PSM with pleural dissemination. Further comparative studies with longer follow-up are needed to evaluate survival by tumor type.
Subject(s)
Hyperthermia, Induced , Peritoneal Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Cancer, Regional Perfusion , Combined Modality Therapy , Cytoreduction Surgical Procedures , Female , Follow-Up Studies , Humans , Neoplasm Recurrence, Local/therapy , Peritoneal Neoplasms/drug therapy , Retrospective Studies , Survival RateABSTRACT
BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is predominantly performed and studied in academic centers. While developing CRS/HIPEC programs in nonacademic hospitals can increase accessibility, its safety and oncological efficacy remains unclear. We evaluated CRS/HIPEC outcomes in a nonacademic setting. METHODS: A single-center descriptive study was conducted using a prospective database. Data of all CRS/HIPEC attempts in peritoneal surface malignancies (PSM) patients from October 1994 to November 2019 were extracted. Surgical and survival outcomes were measured. Center experience was assessed by quartiles of cases. RESULTS: Overall, 856 patients underwent 948 CRS/HIPEC attempts: 788 (83%) completed CRS/HIPECs, 144 (15%) aborted HIPECs, and 16 (2%) complete cytoreductions (CC-0/1) without chemoperfusion. For completed CRS/HIPECs, median peritoneal cancer index was 24 (interquartile range: 10-33) and CC-0/1 rate was 88%. Major complications occurred in 23.5% with 30- and 100-day mortality of 1.0% and 2.3%, respectively. Median overall survival was 68 months (95% confidence interval [CI]: 50-86). Median progression-free survival was 37 months (95%CI: 28-46). Incomplete cytoreduction and major complication rates decreased over time, while mortality remained low and constant. CONCLUSIONS: CRS/HIPEC at a nonacademic center with advanced surgical and auxiliary services is a safe option to treat PSM with favorable surgical and oncological outcomes.
Subject(s)
Chemotherapy, Adjuvant/mortality , Chemotherapy, Cancer, Regional Perfusion/mortality , Cytoreduction Surgical Procedures/mortality , Hyperthermia, Induced/mortality , Hyperthermic Intraperitoneal Chemotherapy/mortality , Peritoneal Neoplasms/mortality , Aged , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/therapy , Prognosis , Prospective Studies , Randomized Controlled Trials as Topic , Survival RateABSTRACT
BACKGROUND: Women 65 years of age or older with epithelial ovarian cancer (EOC) are thought to have a worse prognosis than younger patients. However, no consensus exists concerning the best treatment for ovarian cancer in this age group. This report presents outcomes for patients treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A prospective database of EOC patients treated with CRS/HIPEC (1998-2019) was analyzed. Perioperative variables were compared by treatment including upfront CRS/HIPEC, neoadjuvant chemotherapy plus CRS/HIPEC (NACT + CRS/HIPEC), and salvage CRS/HIPEC, and by age at surgery (< 65 and ≥ 65 years). Survival analysis was performed, and outcomes were compared. RESULTS: Of the 148 patients identified, 42 received upfront CRS/HIPEC, 48 received NACT + CRS/HIPEC, and 58 received salvage CRS/HIPEC. Each group was subdivided by age groups (< 65 and ≥ 65 years). The median overall survival (OS) after the upfront CRS/HIPEC was 69.2 months for the patients < 65 years of age versus 69.3 months for those ≥ 65 years of age. The OS after NACT + CRS/HIPEC was 26.9 months for the patients < 65 years of age versus 32.9 months for those ≥ 65 years of age, and the OS after salvage CRS/HIPEC was 45.6 months for the patients < 65 years of age versus 23.9 months for those ≥ 65 years of age. The median progression-free survival (PFS) after upfront CRS/HIPEC was 41.3 months for the patients < 65 years of age versus 45.4 months for those ≥ 65 years of age. The PFS after NACT + CRS/HIPEC was 16.2 months for the patients < 65 years of age versus 11.2 months for those ≥ 65 years of age, and the PFS after salvage CRS/HIPEC was 18.7 months for the patients < 65 years of age versus 10 months for those ≥ 65 years of age. The median follow-up period for the entire cohort was 44.6 months [95% confidence interval (CI) 34.7-60.6 months]. CONCLUSION: Age and feasibility of complete cytoreduction should be considered when treatment methods are selected for elderly patients. A carefully selected elderly population can benefit significantly from aggressive treatment methods.
Subject(s)
Hyperthermia, Induced , Ovarian Neoplasms , Peritoneal Neoplasms , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Ovarian Epithelial , Child, Preschool , Combined Modality Therapy , Cytoreduction Surgical Procedures , Female , Humans , Hyperthermic Intraperitoneal Chemotherapy , Ovarian Neoplasms/therapy , Peritoneal Neoplasms/therapy , Survival RateABSTRACT
BACKGROUND: Appendiceal goblet cell adenocarcinoma (GCA) is often misclassified and mistreated due to mixed histologic features. In general, cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is standard of care for peritoneal carcinomatosis (PC) from mucinous appendiceal tumors; however, in PC from GCA, data are limited and the role of CRS/HIPEC is controversial. We report outcomes in PC from appendiceal GCA treated with CRS/HIPEC. PATIENTS AND METHODS: A prospective institutional database of 391 CRS/HIPEC patients with appendiceal carcinomatosis from 1998 to 2018 was reviewed. Twenty-seven patients with GCA were identified. Perioperative variables were described. Survival was estimated using the Kaplan-Meier method. RESULTS: GCA occurred in 7% (27/391) of appendiceal CRS/HIPEC patients. Seven (26%) cases were aborted. Two patients underwent a second CRS/HIPEC for peritoneal recurrence. Median age at diagnosis was 53 years (range 39-72 years), and 12 (60%) were female. All underwent previous surgery. Seven (35%) had prior chemotherapy and received a median of 5 cycles (range 3-8). Median PCI was 6 (range 1-39). Complete cytoreduction was achieved in 95% (19/20). Grade III complications occurred in three (15%) patients, and no perioperative deaths occurred. Median follow-up was 97 months. Overall survival at 1, 3 and 5 years was 100%, 74% and 67%, respectively. Progression-free survival at 1, 3, and 5 years was 94%, 67% and 59%, respectively. CONCLUSION: CRS/HIPEC should be considered as the main treatment option for patients with PC from appendiceal GCA. When performed at a CRS/HIPEC specialty center, 5-year OS of 67% can be achieved.
Subject(s)
Adenocarcinoma/therapy , Appendiceal Neoplasms/therapy , Carcinoid Tumor/therapy , Cytoreduction Surgical Procedures , Hyperthermia, Induced , Peritoneal Neoplasms/therapy , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Appendiceal Neoplasms/mortality , Appendiceal Neoplasms/pathology , Carcinoid Tumor/mortality , Carcinoid Tumor/secondary , Chemotherapy, Adjuvant , Combined Modality Therapy , Female , Follow-Up Studies , Goblet Cells/pathology , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/secondary , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: Survival in peritoneal dissemination from appendiceal cancer after complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) varies within each histopathologic subtype. Analyzing patients with unique responses may uncover the mechanisms behind their extreme outcomes. We proposed a method to identify retrospectively and to characterize patients who responded exceptionally well or very poorly within each histopathologic subtype. METHODS: Retrospective review of patients with low-grade mucinous carcinoma peritonei (LGMCP), high-grade MCP (HGMCP), and HGMCP with signet ring cells (HGMCP-S) with complete CRS/HIPEC (CC-0/1) was performed. Patients were divided by recurrence status. Median follow-up was calculated for each. Exceptional responders (ExR) were defined as alive without recurrence after median follow-up of the nonrecurrent group. Poor responders (PoR) were defined as disease recurrence before median follow-up of the recurrent group. Perioperative characteristics were analyzed. RESULTS: LGMCP, HGMCP, and HGMCP-S had 48 (41%), 19 (23%), and 7 (14%) ExR and 11 (10%), 20 (24%), and 20 (39%) PoR, respectively. All ExR had lower median PCI (26 vs. 36 [p = 0.004]; 13 vs. 33.5 [p < 0.001]; 3 vs. 29.5 [p = 0.001]). Fewer LGMCP and HGMCP ExR had abnormal tumor markers (36% vs. 90% [p = 0.003]; 22% vs. 74% [p = 0.003]). More HGMCP and HGMCP-S ExR had CC-0 (vs. CC-1) cytoreductions (84% vs. 50%, p = 0.041; 100% vs. 40%, p = 0.008). CONCLUSIONS: Stratifying patients by recurrence status and follow-up time successfully selects ExR and PoR within each histopathologic subtype. Perioperative characteristics of ExR versus PoR differ across histopathologic subtypes, except for disease burden. Genetic analysis may further elucidate differences and aid in the development of novel targeted therapies.
Subject(s)
Appendiceal Neoplasms/mortality , Chemotherapy, Cancer, Regional Perfusion/mortality , Cytoreduction Surgical Procedures/mortality , Hyperthermia, Induced/mortality , Patient Selection , Peritoneal Neoplasms/mortality , Adenocarcinoma, Mucinous/mortality , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/therapy , Appendiceal Neoplasms/pathology , Appendiceal Neoplasms/therapy , Carcinoma, Signet Ring Cell/mortality , Carcinoma, Signet Ring Cell/pathology , Carcinoma, Signet Ring Cell/therapy , Chemotherapy, Adjuvant , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/therapy , Prognosis , Prospective Studies , Retrospective Studies , Survival RateABSTRACT
BACKGROUND: The role of systemic chemotherapy (SC) before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in appendiceal high-grade mucinous carcinoma peritonei (HGMCP) is controversial. We analyzed the effect of SC prior to CRS/HIPEC in HGMCP. METHODS: A prospective database of CRS/HIPEC procedures for HGMCP without signet ring cells and with signet ring cells (HGMCP-S) from 1998 to 2017 was reviewed. Exclusion criteria was prior surgery >5 regions or >2 regimens of prior SC. Perioperative variables were analyzed. RESULTS: There were 140 HGMCP/HGMCP-S identified: 64 with prior SC (preSC) and 76 without (noSC). Groups were balanced for lymph node status, complete cytoreduction rate, disease burden, complications, and postoperative SC. PreSC had more HGMCP-S, moderately/poorly differentiated histology, and longer time-to-surgery (median: 6 vs 2 months, pâ¯<â¯0.001). Median overall survival (mOS) was 40 vs 86 and median progression-free survival (mPFS) was 19 vs 43 months for preSC vs noSC, respectively (pâ¯=â¯0.006 and pâ¯=â¯0.007). In HGMCP-S subanalysis, mOS was 25 vs 39 and mPFS 16 vs 29 months for preSC vs noSC, respectively (pâ¯=â¯0.188 and pâ¯=â¯0.063). In moderately/poorly differentiated histology subanalysis, mOS was 38 vs 56 and mPFS 18 vs 29 months in preSC vs noSC, respectively (pâ¯=â¯0.199 and 0.082). Prior SC was not linked to improved OS or PFS in non-signet ring HGMCP or well-differentiated histology subanalysis. CONCLUSION: Prior SC was not associated with less disease burden, better cytoreduction rates, or improved clinical outcomes in HGMCP, regardless of histopathologic subtype. Traditional SC agents may not be effective in HGMCP in the neoadjuvant setting.
Subject(s)
Adenocarcinoma, Mucinous/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Appendiceal Neoplasms/therapy , Carcinoma, Signet Ring Cell/therapy , Cytoreduction Surgical Procedures , Hyperthermia, Induced , Peritoneal Neoplasms/therapy , Adenocarcinoma, Mucinous/mortality , Adenocarcinoma, Mucinous/pathology , Adult , Aged , Appendiceal Neoplasms/mortality , Appendiceal Neoplasms/pathology , Carcinoma, Signet Ring Cell/mortality , Carcinoma, Signet Ring Cell/pathology , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Neoplasm Grading , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/pathology , Postoperative Complications , Prospective Studies , Survival RateABSTRACT
BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is standard treatment for peritoneal dissemination from appendiceal cancer (AC); however, its role in high-grade histopathologic subtypes (high-grade mucinous carcinoma peritonei [HGMCP] and HGMCP with signet ring cells [HGMCP-S]) is controversial due to their aggressive behavior. This study analyzed clinical outcomes of high-grade AC after CRS/HIPEC. METHODS: A prospective database of CRS/HIPEC procedures for HGMCP performed from 1998-2017 was reviewed. Perioperative variables and survival were analyzed. RESULTS: Eighty-six HGMCP and 65 HGMCP-S were identified. HGMCP had more positive tumor markers (TM) (CEA/CA-125/CA-19-9) than HGMCP-S (63% vs 40%, p = 0.005). HGMCP had higher Peritoneal Cancer Index (32 vs 26, p = 0.097) and was less likely to have positive lymph nodes (LN) than HGMCP-S (28% vs 69%, p = < 0.001). Complete cytoreduction was achieved in 84% and 83%, respectively. PFS at 3- and 5-years was 59% and 48% for HGMCP vs 31% and 14% for HGMCP-S. Median PFS was 4.3 and 1.6 years, respectively (p < 0.001). OS at 3- and 5-years was 84% and 64% in HGMCP vs 38% and 25% in HGMCP-S. Median OS was 7.5 and 2.2 years, respectively (p < 0.001). LN negative HGMCP-S had longer median PFS and OS than LN positive HGMCP-S (PFS: 3.4 vs 1.5 years, p = 0.03; OS: 5.6 vs 2.1 months, p = 0.021). CONCLUSIONS: The aggressive histology of HGMCP-S is associated with poor OS, has fewer abnormal TM, and is more likely to have positive LN. However, CRS/HIPEC can achieve a 5-year survival of 25%, which may improve to 51% with negative LN.
Subject(s)
Appendiceal Neoplasms/mortality , Carcinoma, Signet Ring Cell/mortality , Chemotherapy, Cancer, Regional Perfusion/mortality , Cytoreduction Surgical Procedures/mortality , Hyperthermia, Induced/mortality , Neoplasm Recurrence, Local/mortality , Peritoneal Neoplasms/mortality , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Appendiceal Neoplasms/pathology , Appendiceal Neoplasms/therapy , Carcinoma, Signet Ring Cell/pathology , Carcinoma, Signet Ring Cell/therapy , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/therapy , Prognosis , Prospective Studies , Retrospective Studies , Survival Rate , Young AdultABSTRACT
OBJECTIVE: Uterine sarcomas (USs) are characterized by poor response to systemic chemotherapy and high recurrence rates. This study evaluates whether the use of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) confers survival benefit in comparison with conventional treatment modalities in patients with recurrent US. METHODS/MATERIALS: A retrospective analysis of patients with recurrent US at a single institution for an 11-year study period was performed. All women with a pathologic diagnosis of leiomyosarcoma, adenosarcoma, endometrial stromal sarcoma, or undifferentiated US were identified. Overall and disease-free survival was estimated using Kaplan-Meier method. Comparisons between the study groups were performed with the log-rank test and Cox regression. RESULTS: A total of 26 patients were identified. Five patients received chemotherapy and/or radiotherapy without surgical intervention, 14 patients underwent surgery alone or a combination of surgery and adjuvant systemic chemotherapy, and 7 patients received cytoreductive surgery with HIPEC. There was no treatment-related mortality in any group, and only 1 patient had grade III-IV surgical complications. Median disease-free survival was 2.4 months for patients with nonsurgical treatments, 5.3 months for patients treated with conventional surgery, and 11.3 months for patients treated with HIPEC. Median overall survival was 35.9 months for patients treated with conventional surgery and 43.8 months for patients treated with HIPEC. CONCLUSIONS: Our study is the first to compare survival outcomes of HIPEC versus conventional therapies for recurrent US and is suggestive of treatment benefit. Further studies with more patients and longer follow-up to evaluate the role of HIPEC in management of this disease are warranted.