Feasibility of a Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Program for Gastrointestinal and Gynecological Cancer Care in Newfoundland and Labrador

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

I read the article by respected Kala Hickey and co-authors with great interest. The article is purely applied in nature and relates to the field of healthcare organization. The results obtained by the authors can be the basis for making a decision on providing the HIPEC therapy in Newfoundland and Labrador. A similar approach can be used for other places, which is a strength of the study. Another strength of the study is the interest in HIPEC. This is a relatively new method of treating peritoneal carcinomatosis, which deserves widespread implementation in medical practice, since it improves the quality of life and prolongs the life of patients with gastrointestinal and gynecological cancers.

The manuscript is very well structured and presented clearly and accessibly. The introduction is written interestingly and well justifies the stated aim. The article uses 55 references, of which 23 references relate to the last five years. All references are relevant and contain only one citation of the authors' work (reference #48). To solve the problem, the authors used an adequate design, correctly selected the inclusion and exclusion criteria. The materials and methods are described in detail and allow the study to be fully reproduced.

The article provides two diagrams illustrating the design of the study. The results are summarized in four tables. The data presented are easy to interpret. The results are presented in full. The authors' conclusions are consistent with the arguments presented. The discussion is detailed and relevant, clearly structured and easy to read.

I see no major comments of the article, except for a few minor points:

1. I am confused by the numbering of the tables. I think it would be better to number the tables sequentially from 1 to 4.

2. Please provide the abbreviations for all tables: Table 1A, LAMN, Table 2A, GI and CRS/HIPEC, Table 1B, IP, and IV.

3. Please do the same with the figures. Provide the abbreviations in the figures in the legends and, if possible, provide the unabbreviated words in the legends.

4. Please form the list of abbreviations in alphabetical order and add the ‘IV’ there.

5. The limitations of the study are described very well in the article, but I would like to highlight the strengths of the study as well. Please add a few sentences at the end of the discussion about how universal your methodology is and whether it can be used for other countries or states.

Author Response

Comment 1: "I am confused by the numbering of the tables. I think it would be better to number the tables sequentially from 1 to 4."

Response 1: Thank you for pointing this out, we have revised the tables to number them sequentially from 1 to 4 to make this more clear and easier to follow. These changes are identified in the revised manuscript in red using the track-changes feature. Please refer to the updated table headings on page 7 (line 244 and 246), and page 8 (lines 276 and 277), as well as the updated text referencing these tables on page 6 (line 233) and page 8 (lines 274, 275)

Comment 2: "Please provide the abbreviations for all tables: Table 1A, LAMN, Table 2A, GI and CRS/HIPEC, Table 1B, IP, and IV."

Response 2: Thank you for recognizing this oversight, these abbreviations have now been defined in a legend below each table and figure. Please refer to page 6 (lines 225-227), page 7 (lines 243 and 245), page 8 (line 253), page 9 (line 286).

Comment 3: "Please do the same with the figures. Provide the abbreviations in the figures in the legends and, if possible, provide the unabbreviated words in the legends."

Response 3: Please refer to response 2 as this addresses both comment 2 and 3.

Comment 4: "Please form the list of abbreviations in alphabetical order and add the ‘IV’ there."

Response 4: The list of abbreviations has been updated to include IV as well as two other abbreviations noted by another reviewer. They have been arranged in alphabetical order. Please refer to page 12 between lines 426 and 427

Comment 5: "The limitations of the study are described very well in the article, but I would like to highlight the strengths of the study as well. Please add a few sentences at the end of the discussion about how universal your methodology is and whether it can be used for other countries or states."

Response 5: We appreciate your acknowledgement of the strengths of our study. We have included a statement regarding the universal application of our methods. Please refer to page 11 (lines 398-400).

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors,

I read with interest your paper: “Feasibility of a Hyperthermic Intraperitoneal Chemotherapy 2 (HIPEC) Program for Gastrointestinal and Gynecological Can- 3 cer Care in Newfoundland and Labrador”, It appears a retrospective analysis of the activity of high volume center.

Peritoneal carcinomatosis (PC) arises from primary peritoneal malignancies (e.g., mesothelioma, serous carcinoma) or secondary metastases from gastrointestinal (GI) and gynecological cancers. It is associated with poor prognosis, significantly reducing survival. Traditionally, PC was managed palliatively, but cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results, improving outcomes in select patients.

CRS/HIPEC is a promising approach for select patients with PC from CRC, gastric cancer, PMP/AMN, and EOC. Patient selection, tumor burden (PCI score), and completeness of cytoreduction are key determinants of success. While HIPEC remains controversial in some cancers, evidence supports its use in well-defined patient populations.

The article is very well written and deals with a number of conditions common to the HIPEC procedure.

It is not very clear, however, what the objective of the study is: to already propose a regional reference program for the execution of the procedures or to draw some hints from it? In the first case it would not be obvious from the text and should be focused on this by subclassifying the proposal by tumour type and possible related snags in management planning. In the second case, perhaps I would streamline the form, but making the need for an article on this stand out and already make a concrete proposal of the study objective.

I suggest to add other center experience such as: DOI: 10.31083/j.ceog4906143

I would summarise the contents by going straight to the proposed feasibility treatment.

Author Response

Comment 1: “It is not very clear, however, what the objective of the study is: to already propose a regional reference program for the execution of the procedures or to draw some hints from it? In the first case it would not be obvious from the text and should be focused on this by subclassifying the proposal by tumour type and possible related snags in management planning. In the second case, perhaps I would streamline the form, but making the need for an article on this stand out and already make a concrete proposal of the study objective.”

Response 1:

We appreciate the opportunity to clarify the objective of our study.
The primary objective was to determine the combined population size of gastrointestinal and gynecological oncology patients meeting criteria to undergo CRS/HIPEC in Newfoundland. In doing so, we aimed to determine whether an appropriate patient volume exists to fulfill the recommendations for new program implementation outlined by the Canadian HIPEC Collaborative Group and Peritoneal Surface Oncology Group International (one case monthly, 20 cases annually). The objective statement has been revised in the manuscript to more clearly reflect this. Please refer to page 4 (lines 189-193).

Notably, we do not intend to discuss the details/considerations of program/protocol development as this has already been published by a member of our research team in a separate manuscript. (Please refer to reference #48)

Comment 2: “I suggest to add other center experience such as: DOI: 10.31083/j.ceog4906143”

Response 2: We appreciate you bringing this reference to our attention. The reference has been reviewed and its findings included in the revised manuscript paragraph reviewing the evidence for CRS/HIPEC in Epithelial ovarian cancer. Please refer to page 3 (lines 139,141-143) and page 4 (lines 151-154) as well as the bibliography reference #56.

Reviewer 3 Report

Comments and Suggestions for Authors

The major goal of this manuscript is to offer convincing patient data (primarily the number of eligible patients) for establishment of a combined surgical and gynecological oncology CRS-HIPEC (cytoreductive surgery plus heated intraperitoneal chemotherapy) program within the province of Newfoundland and Labrador (NL), Canada.  Through retrospective analysis of patient registry and clinical data from Jan 1, 2020 – Dec 31, 2020, 31 patients were identified to be potentially eligible for the proposed CRS-HIPEC program, which meets the threshold of a minimum of one case per month recommended by Canadian HIPEC Collaborative Group to maintain competency and achieve good outcomes. Therefore, the authors conclude that the patient volume in NL supports collaborative efforts to establish a CRS-HIPEC program that would benefit gastrointestinal and gynecological cancer patients within the province. The manuscript is well written and organized.  It is easy to follow. Some comments are listed below.

1.  I would appreciate if the authors could state reasons why more data before 1/1/2020 and after 12/31/2020 were not included.  If more data were available, why would the authors choose this particular time window?

2.  Please include PCI and GO in the table of “Abbreviations”.

3.  In line 179, “… not available them.” should be changed to “… not available to them.”

Author Response

Comment 1: "I would appreciate if the authors could state reasons why more data before 1/1/2020 and after 12/31/2020 were not included.  If more data were available, why would the authors choose this particular time window?"

Response 1: We recognize and appreciate the question regarding the limitations associated with the use of a one year data collection period. The reason for this is based on the fact that this project initially started with a focus solely on the gynecological oncology population for which data was collected over a one year period by a medical student. Following this, the idea and possible impact of a collaborative approach between gynecological and surgical oncology was identified. Therefore, we completed a retrospective review for the gastrointestinal population during the same time frame in order to match the existing gynecology dataset. Future research endeavours could certainly benefit from inclusion of a larger data collection period in order to better capture annual variability and reduce the possible confounding impact of the COVID 19 pandemic as noted in the limitations paragraph of our manuscript.

Comment 2: "Please include PCI and GO in the table of “Abbreviations”."

Response 2: We thank you for noting this oversight. We have updated the table of abbreviations to include these as well as one other identified by another reviewer and have arranged them in alphabetical order. All changes are represented in the revised manuscript document in red via the track-changes method. Please refer to page 12, between lines 426 and 427.

Comment 3: "In line 179, “… not available them.” should be changed to “… not available to them.”"

Response 3: We appreciate your recognition of this missing word. The sentence has been revised to include this. Please refer to page 4 line 179.

Reviewer 4 Report

Comments and Suggestions for Authors

There is no point in publishing this study. Everything is already known.

Author Response

Comment 1: "There is no point in publishing this study. Everything is already known."

Response 1: Thank you for your expertise in reviewing our manuscript. While we appreciate that our paper does not bring forth new scientific evidence, we feel that it does in fact provide data to support effective change in practice. These results provide a basis for decision making regarding the provision of HIPEC therapy in the Canadian province of Newfoundland. Our study is the first of its kind to assess the population size meeting criteria for this therapy in our province. It provides us with important epidemiological data and supports the hypothesis that an adequate patient population exists to fulfill the recommendations outlined by the Canadian HIPEC collaborative group for a specialized and centralized therapy. The results of this feasibility study provide support for program implementation to provincial agencies as well as the national oncology community and once established will improve access to care for this population.

Round 2

Reviewer 4 Report

Comments and Suggestions for Authors

Again there is no novelty or real science here. This is a matter of organization not science. 

Author Response

We appreciate your review. As per the editors response to your comment, we have addressed their recommendations in an updated version of our manuscript as a means to elaborate on the novel impact our population provides. 

Notably, the population of Newfoundland and Labrador represents a group of patients with the highest incidence and mortality from colorectal and gastric cancers in Canada, as well as the highest rate of familial colorectal cancer in the world.

The implementation of a CRS/HIPEC program in NL will allow for collection of data from a population with unique genetic alterations with the potential to provide novel insight into the management of peritoneal surface malignancy in these specific groups.