Cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for children, adolescents, and young adults: the first 50 cases

Our plain-English summary of Cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for children, adolescents, and young adults: the first 50 cases, by A. Hayes-Jordan, H. Green, H. Lin, et al (Annals of Surgical Oncology, 2015).

The study

• Authors: A. Hayes-Jordan, H. Green, H. Lin, P. Owusu-Agyemang, R. Mejia, R. Okhuysen-Cawley, J. Cortes, N.E. Fitzgerald, M.F. McAleer, C. Herzog, W.W. Huh, P. Anderson
• Journal: Annals of Surgical Oncology
• Published: 2015;22(5):1726-32
• Cited by: 67 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Extensive peritoneal metastatic disease is rare in children. Although usually manifested as carcinomatosis in adults, sarcomatosis is more common in children. The authors began a pediatric hyperthermic intraperitoneal chemotherapy (HIPEC) program, and this report describes their initial results from the first 50 pediatric, adolescent, and young adult patients.

Methods: A single-institution, retrospective study investigated the first 50 cytoreductive surgeries and HIPEC by one surgeon for patients 3-21 years of age. The HIPEC was added to chemotherapy and radiotherapy treatment. Demographics, outcome, and complications were recorded.

Results: The median follow-up period for the surviving patients was 21.9 months. The most common diagnoses were desmoplastic small round cell tumor (n = 21), rhabdomyosarcoma (n = 7), mesothelioma (n = 4), and other carcinoma (n = 17). Multivariate analysis showed that patients treated with HIPEC and an incomplete cytoreduction had a greater risk for recurrence than those who had a complete cytoreduction (p = 0.0002). The patients with a higher peritoneal cancer index (PCI) (i.e., a large tumor burden) had a median overall survival (OS) time of 19.9 months relative to the patients with a lower PCI score, who had a median OS of 34 months (p = 0.049). The patients without complete cytoreduction had a median OS of 7.1 months compared with 31.4 months for the patients with complete cytoreduction (p = 0.012). No perioperative mortalities occurred. The incidence of major complications was 28 %.

Conclusion: Cytoreductive surgery and HIPEC with a programmatic approach for patients 3-21 years of age is unique. The best outcome was experienced by patients with desmoplastic small round cell tumor and those with complete cytoreduction. Complete cytoreduction for patients without disease outside the abdominal cavity at the time of surgery affords the best outcome.

In plain English

This study did not examine asbestos exposure. It retrospectively reviewed the first 50 patients, aged 3 to 21, treated by one surgeon at MD Anderson Cancer Center in Houston. They had tumor-removal surgery and heated cisplatin chemotherapy circulated through the abdomen (HIPEC). The most common diagnosis was desmoplastic small round cell tumor (21 patients). Table 1 lists 4 mesothelioma patients, the text 3. Table 2 gives each one's surgery and 30-day complications, but their survival was not reported separately. Patients with complete removal, or less than 2.5 cm of tumor left, had a median overall survival of 31.4 months (confidence interval 18.2 months to an upper limit given as NR). Those left with more than 2.5 cm had a median of 7.1 months (confidence interval 2.0 to 14.4 months). Patients with desmoplastic small round cell tumor had better overall survival than other patients. No patients died around the time of surgery, and 28 % had severe complications. The authors concluded that HIPEC is safe and perhaps effective for some pediatric soft tissue sarcomas. They said the small sample and mixed tumor types limit firm conclusions.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Single-institution retrospective analysis of consecutive patients treated by one surgeon; the early patients were part of a phase 1 trial
• Who was studied: 50 pediatric, adolescent and young adult patients aged 3 to 21 years at the University of Texas MD Anderson Cancer Center-Children's Cancer Hospital, Houston; dates not given. Diagnoses included desmoplastic small round cell tumor (21), rhabdomyosarcoma (7) and, according to Table 1, mesothelioma (4); the text gives 3 mesothelioma patients. Patients from the later phase 2 trial were not included.
• Exposure: No asbestos or fiber exposure was studied. The treatment studied was cytoreductive surgery plus closed-technique HIPEC with 100 mg/M2 of cisplatin at 41 degrees C, added to chemotherapy and, for desmoplastic small round cell tumor patients, postoperative total abdominal radiation.
• Main results:
  • Patients with complete (CR0) or near-complete (CR1) cytoreduction had a median overall survival of 31.4 months (confidence interval 18.2 to NR). Patients with CR2 (more than 2.5 cm of tumor remaining) had a median overall survival of 7.1 months (CI 2.0 to 14.4 months).
  • No patient with incomplete cytoreduction survived longer than 15 months.
  • Desmoplastic small round cell tumor patients had significantly better overall survival (p = 0.038) than patients with other histologies, but not better disease-free survival (p = 0.777).
  • Patients with a peritoneal cancer index lower than 16 had a median disease-free survival of 34 months, compared with 19.9 months for those with an index of 16 or higher (p = 0.047). Overall survival did not differ statistically by peritoneal cancer index (p = 0.264).
  • Patients with disease outside the abdominal cavity (4 of 50, per Fig. 4) had worse disease-free survival (p = 0.003) but did not differ in overall survival (p = 0.272).
  • The 8 patients with liver metastasis after neoadjuvant chemotherapy had poorer disease-free survival (p = 0.013) but did not differ in overall survival (p = 0.456).
  • Table 2 lists four mesothelioma patients (numbers 4, 9, 11 and 44) individually, with organs resected and 30-day complications. For example, patient 9 had a cholecystectomy and splenectomy with no complications, and patient 44 had spleen and pelvic resection with skin separation. Survival for mesothelioma patients was not reported separately.
  • No deaths occurred around the time of surgery (perioperative), and no patients had postoperative bleeding; deaths did occur during follow-up.
  • 28 % of patients had severe postoperative complications, including partial small bowel obstruction, wound infection, urinary tract infection and renal insufficiency.
  • Disease-free and overall survival did not differ by age, using cutoffs of 10 or 12 years.
  • 18 of 24 pelvic tumor resections were done without removing the rectum, and no tumors recurred in the pelvis.
  • The 1-year survival rate in this study was 89 %. The discussion sets this beside a rate of 80 % in an earlier report on desmoplastic small round cell tumor.
• The authors' conclusion: The authors concluded that HIPEC is safe and perhaps effective for some pediatric-type soft tissue sarcomas. They also concluded that complete cytoreduction is a critical component in extending survival, regardless of histology.
• Limitations the authors state:
  • Small sample size and diverse histologies; further study is needed for definitive conclusions.
  • For most tumor types other than desmoplastic small round cell tumor, the data were insufficient to conclude whether the treatment is effective.
  • Too few patients to decide whether HIPEC should be offered to patients with disease outside the peritoneum.

Topics

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, HIPEC, Chemotherapy, Desmoplastic Small Round Cell Tumor, Mesothelioma, Carcinoma, Multivariate Analysis, Peritoneal Cancer Index (PCI).

Related studies

• A Novel Tool for Predicting Major Complications After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy — J.M. Baumgartner, T.G. Kwong, et al. (2016)
• Early recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) — G.H.C. Tan, C.S. Chia, et al. (2018)
• The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — S. Kusamura, P.A. Torres Mesa, et al. (2016)
• Outcomes of Cytoreductive Surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients older than 70 years; survival benefit at considerable morbidity and mortality — K.I. Votanopoulos, N.A. Newman, et al. (2013)
• Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent or progressive diffuse malignant peritoneal mesothelioma: clinicopathologic characteristics and survival outcome — C. Ihemelandu, L. Bijelic, et al. (2015)
• Morbidity of the abdominal wall resection and reconstruction after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) — M.F. Nunez, A. Sardi, et al. (2015)

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