At CancerCare Manitoba (CCMB) the Clinical Practice Guidelines Initiative (CPGI) seeks to improve patient outcomes through the development, dissemination, implementation and evaluation of guidelines for the management of common clinical scenarios encountered by cancer patients throughout the province. This clinical practice guideline was created through the efforts of a large interdisciplinary group from CCMB in collaboration with community partners. Members of the CCMB Gastro-Intestinal Disease Site Group (DSG) and Departments of Gastroenterology, Medical Oncology, Radiation Therapy, Thoracic Surgery, and General Surgery have participated in its development.# I. Introduction
Gastric cancer is a low incidence cancer with high mortality rates in Canada. 5 Surgery for gastric cancer is complex and of variable quality, at least in low incident non-Asian countries, with potential for morbidity and mortality. 6 Similarly, the fairly recent advent of adjuvant and neoadjuvant therapies for gastric cancer has made the landscape of treatment of this serious illness complex and at times confusing. Provision of substandard care decreases the survival rates of gastric cancer, and mechanisms to provide clarity, standardization and competence of treatment will be of significant benefit to the Manitoban population.
Thus, the purpose of this guideline is to outline the appropriate work-up and treatment of potential curable gastric carcinoma in Manitoba.
The guideline does not cover the following treatment scenarios:
- Carcinoma of the gastro-esophageal junction (GEJ), gastric GIST, gastric neuroendocrine tumours, and gastric lymphoma - Unresectable and/or metastatic gastric carcinoma - Gastric metastases from other primary tumours
The guideline is intended to outline the appropriate investigations of a known or suspected gastric carcinoma, as well as an overview of the appropriate use of chemotherapy, radiotherapy and surgery in treating this disease. The reliance on multidisciplinary care is also emphasized.

# III. Guideline Methodology
Using standard search strategies, the clinical practice guideline office performed a review of published literature to identify all existing published guidelines. Committee members reviewed each document and assessed for quality and appropriateness. The committee met in person on March 2, 2018 to review this evidence and for in-depth discussion.
The plan of review was as follows:
- Adopt a guideline(s) if deemed appropriate - Adopt portions of guidelines if no single document was of sufficient quality - Create a new guideline de novo if guidelines were of poor quality or not appropriate to our patient population or health system
The review meeting consisted of evaluating each guideline on the following criteria:
- Does it cover our stated purpose and scope?
- Is it evidence-based?
- Is it missing any significant areas or evidence with respect to work up and treatment?
- Are there general concerns regarding content or format?
Published Guideline Review
Ten guideline documents were identified in the literature search. On further review, two were found to be frankly out of scope of our goal and discarded. An in-depth discussion of the remaining eight occurred. Two guidelines were essentially a part A and B from the same organization (Cancer Care Ontario) and were considered a single comprehensive document for the purposes of our review. One further guideline (a 2018 guideline from the BC Cancer Agency) was reviewed after the in-person meeting, but was deemed to reflect similar information to the other documents. The ten articles reviewed are listed in Table 1.

# Internal and External Review
Internal and external peer reviews were pursued, the results of which are appended to this guideline. The internal review consists of revision by the working group. An external review was undertaken by one radiation oncologist who completed a full review of the guideline document and submitted practitioner feedback comments. Feedback was reviewed and discussed.
Table 1. List of published guidelines reviewed.

# Conclusions
The group unanimously agreed to the adoption of the Cancer Care Ontario guidelines for the curable treatment of gastric cancer. 1,2 These guidelines were felt to be comprehensive and evidence-based.
Their guideline documents were also found to be easily readable for physicians and surgeons, with an appropriate amount of detail and explanation.
Of mention, the ESMO guideline was deemed to be of equivalent quality and scope. We favoured the Ontario guideline for its depth of explanation, including methodology, and readability, as well as its Canadian origin (and thus applicable to our health system). The BC guideline was similarly of good quality but only covered the surgical aspects of care, so not as comprehensive as required for our purposes. It should be noted that all three guidelines deliver essentially the same message.
The CCO guideline relating to staging and surgery dates from 2017 and is contemporaneous in all aspects. No alterations, or qualifying statements, were recommended by the committee. In regards to the non-surgical aspects of treatment, however, this aspect of the guideline is dated, with no other published guidelines in our search to replace it. Thus the committee felt it appropriate to adopt the 2011 guideline as a base for our recommendation and then add further data to it, as an informal mechanism of updating. The qualifying statements agreed to are listed below: 1. Clinical Trials. We wish to encourage enrollment of gastric cancer patients into clinical trials when feasible, and locally available. The landscape of gastric cancer treatment has seen significant improvements over the last two decades, since the publication of the first major randomized control trial showing benefit of adjuvant therapy in gastric cancer 3 ; yet there is significant work still needed to improve our survival statistics and quality of life. Clinical trial enrolment is felt to be beneficial in that it ensures current high quality care and allows for the development of new treatment paradigms. It does require uncoerced and informed consent of the patient, with their acceptance of the inherent unknowns in experimental regimens, and often has strict enrolment criteria as well as limitations to where care can be delivered; as such, trial enrolment is not for everyone.

# Guideline Title Guideline Group Year
- FLOT perioperative chemotherapy. The choice of perioperative chemo in stage 1B to 3 cancers should include the option of the FLOT (docetaxel, oxaliplatin, and fluorouracil/leucovorin) regimen. 7 The German AIO group published their results on this regimen in abstract form at ASCO 2017. These results show a dramatic improvement over the previous standard of ECF (epirubicin, cisplatin, and fluorouracil). 4 As the abstract results are extraordinarily compelling, the Canadian gastric cancer medical oncology community has widely adopted this protocol and we concur with that approach. FLOT should be considered for all advanced stage gastric cancer patients who are healthy enough for aggressive chemotherapy. As this data is still preliminary, review of patients through P and T or case conference mechanisms is prudent. Upon publication of final results, strong consideration to placing this regimen on formulary is recommended, assuming the final publication is congruent with the published abstract.
- Additional trials. Several non-practice changing trials were discussed at our committee meeting.
The CRITICS trial was one such trial. 8 This trial randomized patients to post-operative chemoradiotherapy versus chemotherapy alone in patients receiving preoperative chemotherapy and surgery for gastric cancer. The study found that a postoperative chemoradiotherapy regimen did not improve overall survival compared to chemotherapy therapy alone. It did note poor compliance to both postoperative regimens and sits as a reminder that all studies show patients to be less apt to tolerate therapy in the postoperative period. The ARTIST trial was also briefly discussed. 9 This trial compared postoperative chemotherapy to postoperative chemoradiotherapy in patients who had recovered from a D2 lymphadenectomy. This trial did not find an advantage to chemoradiotherapy in the intention-to-treat analysis, but post hoc analysis did reveal a potential advantage to that strategy in node positive patients, as well as those with intestinal-type histology. The relevance of this trial to our local population is also uncertain, as a majority of patients do not receive extended lymphadenectomy currently; as such, it does not supplant the information gained for the SWOG trial 3 , but does provide for some reflection in the utility of radiation in the minority of patients with extended lymphadenectomies. Finally, there must be some note that many of our gastric cancer studies come from Asian populations, and in general, they report survival rates well in excess of what is seen in Western populations, regardless of what treatment protocol is used. The differences in patient population, screening, centralization of care, and treatment strategies make applicability of many Asian trials to be challenging to our provincial context. Thus, we must exercise caution in interpreting such data. 

# GUIDELINE OBJECTIVES
To develop recommendations on the optimal surgical management of gastric cancer in Ontario.

# TARGET POPULATION
These recommendations apply to adult men and women with Stage I to IV gastric cancer (specifically gastric adenocarcinoma) who are being considered for surgery. Gastroesophageal junction (GEJ) tumours and early gastric cancers are excluded because they require additional considerations. 

# INTENDED USERS
Intended users of this guidance document are surgeons, gastroenterologists, medical oncologists, radiation oncologists, and the multidisciplinary team who treat gastric cancer.

# RECOMMENDATIONS, KEY EVIDENCE, AND INTERPRETATION OF EVIDENCE Recommendation 1
Endorsed from Lerut et al. 2012 :
- All patients diagnosed with gastric cancer should be discussed at a multidisciplinary team meeting.  In patients with newly diagnosed gastric cancer, CT scan of the chest and abdomen should always be performed.  Endoscopic ultrasound (EUS) can be considered in patients planned for curative treatment on the basis of clinical presentation and/or CT. Fine -needle aspiration cytology of suspicious lymph nodes or metastases can be considered if tech nically feasible.  The following examinations can be considered for specific indications: PET scan, magnetic resonance imaging, laparoscopy.

# Qualifying Statements for Recommendation 1
- As the accuracy for CT scans in detecting M1 disease is 81% , diagnostic laparoscopy may allow patients to avoid a laparotomy in up to 44% of cases of advanced stage cancer . Both Scottish Intercollegiate Guidelines Network (SIGN)  and Society of American Gastrointestinal and Endoscopic Surgeons (SAGES)  guidelines suggest diagnostic laparoscopy in patients with clinically suspected T3 and T4 cancers, or those at higher risk for M1 disease, such as poorly differentiated cancers and those with a higher nodal burden. Diagnostic laparoscopy should be performed p rior to starting chemotherapy for patients in whom a neoadjuvant approach is considered. Washing may increase the accuracy of diagnostic laparoscopy.  PET and MRI may be useful for further characterization of liver lesions, in clinical scenarios in which treatment plans would be changed by the finding of metastatic disease, but should not be routinely performed.  EUS should only be performed if results may change management plans (i.e., to assess for local invasion, nodal status or metastatic spread).

# Key Evidence for Recommendation 1
- Key evidence derived from one clinical practice guideline conducted by Lerut at al.  of the Belgian Health Care Knowledge Centre.

# Interpretation of Evidence for Recommendation 1
- There was agreement among the Working Group members that the overall certainty of the evidence was moderate.  The Working Group considered accurate staging of each patient to be of paramount importance in order for patients to be provided appropriate treatment. Therefore, the Working Group was unanimous in their opinion that patients would also value the importance of accurate staging, although patient input was not sought.  The desirable effect (i.e., accurate staging) is large as patients who are improperly staged will not be provided with appropriate treatment. At the same time, the undesirable effects (morbidity of the staging investigations) are manageable in this population. The Working Group believed the desirable effect (accurate staging) is large relative to the undesirable effects (potential increased morbidity) in this population of patients because inaccurate staging will result in patient being treated inappropriately, either by under-treating or over-treating them.
- The evidence is generalizable to the entire population of gastric cancer patients.  The Working Group believed that all interpretations of the evidence for staging of gastric cancer patients would be similar. showed fewer gastric cancer-related deaths in patients undergoing a D2 LND for all Tstages (gastric cancer related deaths were 48% in D1 vs. 37% in D2, p=0.01, per protocol analysis) .

# Interpretation of Evidence for Recommendation 2
- See Section after Recommendation 4.

# Recommendation 3
- At least 16 lymph nodes should be assessed for adequate staging of curative -resected gastric cancer.

# Qualifying Statements for Recommendation 3
- American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) guidelines  state that 16 lymph nodes are necessary for adequate staging.  Studies  suggest that removal and examination of more than 16 nodes may improve survival and increases accuracy of staging by decreasing under staging which leads to stage migration.

# Key Evidence for Recommendation 3
- One systematic review  reported significantly improved disease -free survival (DFS) as the number of lymph nodes harvested increased, especially when more than 15 nodes were retrieved, and concluded that 16 lymph nodes should be harvested as a minimum. More current studies of moderate quality  also report that harvesting more than 15 nodes significantly improved survival.

# Interpretation of Evidence for Recommendation 3
- See Section after Recommendation 4.

# Recommendation 4
- Surgery for gastric cancer should aim at achieving an R0 margin.   guidelines suggest 4 cm margins in order to assure negative margins, while the Japanese Gastric Cancer Treatment Guidelines  suggest that margins of 3 cm for T1/T2 cancer and 5 cm for T3/T4 cancers be obtained.  Intra-operative frozen section analysis should be considered in cases where there is concern about a high risk of positive margin.  Cancers with higher T and N stage, and higher grade tumours, such as diffuse -type histology including signet ring carcinoma, are more likely to have microscopic margins involved, and intra-operative planning or neoadjuvant therapy should take these factors into consideration.  For patients with poor biology (>5 lymph nodes positive, diffuse -type histology including signet ring carcinoma), an extended resection of the adjacent organs or intra-thoracic esophagus may not result in improved long-term survival, as multivariable analyses in many studies have shown that tumour biology may be a stronger determinant of outcomes than a positive margin.  Extended resection should be undertaken selectively and with multidis ciplinary discussion.

# Key Evidence for Recommendation 4
- Data from one study suggest that margins of 5 cm for T3/T4 cancer and 3 cm for T1/T2 cancers are sufficient to obtain resection margins negative for microscopic cancer .  Median overall survival (OS) and median recurrence-free survival (RFS) for patients was significantly better in those with proximal margins of 3.1 to 5.0 cm compared with margins 3.0 cm (48.1 vs. 29.3 months, p=0.01; and 38.9 vs. 21.1 months, p=0.02, respectively). Median OS and median RFS for patients with margins >5.0 cm were not significantly different than those with proximal margins of 3.1 to 5.0 cm. However, the OS and RFS advantage of a proximal margin 3.1 cm was only associated with Stage I disease only and was not associated with Stage II or III disease .

# Interpretation of Evidence for Recommendation 4
- See Section after Recommendation 4.

# Interpretation of Evidence for Recommendations 2, 3 and 4.
- There was agreement among the Working Group members that the overall certainty of the evidence was moderate based on the entire body of the evidence.  Although the Working Group looked at survival, mortality, reoperation rates, and RFS, OS was considered to be the most important outcome, followed by RFS. The Working Group was unanimous in their opinion that patients would also value the increased survival benefit associated with each of the surgical parameters evaluated (extent of lymphadenectomy, number of lymph nodes retrieved, and minimal gross margins) although patient input was not sought. The Working Group valued survival when drafting the recommendations as they believed that the morbidities associated with each of these surgical parameters were manageable.  The desirable effect is increased survival. The undesirable effects (morbidity) are manageable in this population. The Working Group believed the desirable effect (longer survival) is large relative to the undesirable effects (extra morbidity) in the selected group of Stage III patients especially since inadequate LND, positive margins, and retrieval of an inadequate number of lymph nodes are all asso ciated with disease recurrence.  The evidence is generalizable to the entire gastric cancer population as defined in this guidance document.1  The Working Group believed that there might be an alternate interpretation of the evidence for D2 versus D1 LND if the focus remains on several negative trials available and not on the compelling subgroup analysis of these trials and the emerging long-term survival benefits in ongoing trials.

# Recommendation 5
- In the metastatic setting, nonsurgical management options are preferred in patients without symptoms.  In the metastatic setting, surgery should only be considered for palliation of symptoms that cannot be addressed through less-invasive means (i.e., radiation, chemotherapy, stenting).

# Qualifying Statements for Recommendation 5
- As the rate of complications appears to be highest in more extensive resections, a palliative total gastrectomy should be performed only in exceptional circumstances, and with multidisciplinary discussion. Key Evidence for Recommendation 5  In one systematic review of 59 studies, procedure-related morbidity occurred in all types of surgical interventions and irrespective of the intent of the surgery. Morbidity ranged from 3.8% to 49% for gastrectomy and 14% to 21% for non-resectional surgeries . In the literature update, procedure-related morbidity in moderate-quality noncurative studies ranged from 15.1%  to 88.8% for gastrectomy and 11.5%  to 21% for non-resectional surgeries.  In the systematic review by Mahar et al. , procedure-related mortality was lower in palliative resections (0% to 7%) compared with either non -curative (0% to 21%) or not otherwise specified surgeries (0% to 20.4%). The mortality rate for gastrectomy performed for any intent was 0% to 21% whereas the mortality rate for non -resectional surgeries was 0% to 39% . In the literature update, which included all moderate quality studies, procedure-related mortality for gastrectomy performed in noncurative studies was 1.1%  to 9.1% , whereas the mortality rate for nonresectional surgeries in non-curative studies was 4.8%  to 10% .  The REGATTA trial  showed no survival benefit of gastrectomy + chemotherapy over chemotherapy alone (25.1% vs. 31.7%) in patients with non -curable gastric cancer (hazard ratio , 1.09; 95% CI, 0.78 to 1.52; p=0.70), and more complications for patients in the gastrectomy + chemotherapy arm.

# Interpretation of Evidence for Recommendation 5
- There was agreement among the Working Group members that the overall certainty of the evidence was moderate.  Although the Working Group looked at survival, morbidity, mortality, and quality of life (QOL), morbidity and QOL (where available) were considered to be the most important outcomes. The Working Group was unanimous in their opinion that patients would also likely value these outcomes, although patient input was not sought.  The Working Group valued OS over toxicity when drafting the recommendations as they felt that the toxicities were manageable.  The desirable effect (i.e., better QOL, less morbidity) is probably not large, especially for Stage IV patients in whom the goal of surgery is not palliation of symptoms. At the same time, the undesirable effects are moderate. The mortality rates for surgery in Stage IV gastric cancer can be high especially when the surgery is not performed for CCMB, Disease Management: Guideline for the Curative Treatment of Gastric Cancer p.17
Date Updated: December 2018 palliation of symptoms. The Working Group believed the desirable e ffect (better QOL) was not large relative to the undesirable effects (mortality) and should, therefore, only be performed for palliation of symptoms. If the surgery is not likely to improve QOL, it should not be done.  The evidence is not generalizable to the entire Stage IV gastric cancer population as defined in this guidance document.  The Working Group believed that the REGATTA trial  may be interpreted differently by others. REGATTA was stopped early for futility and possible harm in the surgery arm. It is conceivable that these data may be interpreted as meaning that survival was equivalent in the surgery and the surgery + chemotherapy arms, but most are not making this interpretation.

# Recommendation 6
- Given evidence that higher-volume centres are associated with lower rates of procedure-related mortality, patients should be referred to higher-volume centres for surgical resection.  Gastric cancer surgery should be performed in centres with sufficient support to prevent or manage complications (e.g., interventional radiology, anesthesia, level 1 intensive care unit).

# Qualifying Statements for Recommendation 6
- In most studies, higher-volume centres are associated with improved outcomes. There is no common definition of a high-volume centre within the studies; however, it should be noted that five or fewer annual cases are considered low or very low volume in all studies.  An expected 30-day or in-hospital peri-operative mortality should be less than 5%. This is based on published mortality rates from high-volume centres, as well as the "Hepatic, Pancreatic and Biliary (HPB) Tract Surgical Oncology Standards" (EBS#17-2) , which recommends a 30-day or in-hospital mortality rate of less than 5% for major pancreatic resection and 3% for anatomical liver resection. As these procedures are more complicated than gastric cancer surgery, it is reasonable to expect a similar or lower mortality rate.  Hospitals performing gastric cancer surgery should know their mortality rates, and recognize that lower volumes create larger confidence intervals for mortality estimates.

# Key Evidence for Recommendation 6
- In one systematic review containing 22 studies looking at institutional volumes, procedure-related morbidity was not significantly different in high-volume compared with low-volume hospitals (19% to 46.5% in high-volume hospitals vs. 19% to 43% in low-volume hospitals). However, meta-analysis of procedure-related mortality favoured high-volume hospitals (OR, 0.73; 95% CI, 0.65 to 0.81; p<0.00001). Improved five-year survival was significantly associated with higher institutional volumes in three of seven studies that evaluated this outcome .  In the updated literature search, procedure-related mortality was not significantly different in high-versus low-volume hospitals in four of the five studies evaluating this outcome . However, in 2013, Dikken et al.  reported that procedurerelated mortality significantly favours high-volume hospitals (OR, 0.64; 95% CI, 0.41 to 0.99; p=0.025). The updated literature search only yielded moderate quality non-RCTs.

# Interpretation of Evidence for Recommendation 6
CCMB, Disease Management: Guideline for the Curative Treatment of Gastric Cancer p.18
Date Updated: December 2018  There was agreement among the Working Group members that the overall certainty of the evidence was low to moderate.  Although the Working Group looked at mortality (especially 30-day and in-hospital mortality) and morbidity, the Working Group was unanimous in their opinion that patients would value mortality as an assessment of surgeon and/or institutional volumes, although patient input was not sought.  The desirable effect (i.e., lower short-term mortality) is large. At the same time, the undesirable effects (i.e., death) are not small. The Working Group believed the desirable effect (living) was larger relative to the undesirable effects (death).  The evidence is generalizable to gastric cancer surgery in all institutions.  The Working Group believed that others may have slightly different interpretations of the volume data by setting definite numerical volume standards, whereas in the present guidance document the focus was on mortality rate instead.

# Recommendation 7
- Quality metrics for lymph nodes, margins, peri-operative mortality, and oncologic outcomes should be met regardless of surgical technique (e.g., open or minimally invasive).

# Qualifying Statements for Recommendation 7
- While laparoscopic resection has been shown to be equal or superior to open surgery for short-term outcomes, there is no evidence regarding long-term cancer outcomes. Several ongoing randomized trials will report on oncologic survival.

# Key Evidence for Recommendation 7
- Short-term outcomes (e.g., blood loss, time to first flatus, length of hospital stay, and post-operative complications) favour laparoscopic compared with open gastrectomy . This is based on one systematic review and several more recent primary studies. Long-term cancer-related survival results are currently being examined in several RCTs.

# Interpretation of Evidence for Recommendation 7
- There was agreement among the Working Group members that the overall certainty of the evidence was moderate.  Although the Working Group looked at short-term outcomes (blood loss, time to first flatus, length of hospital stay, post-operative complications, hospital mortality rates, and surgical time) and long-term outcomes (survival), no long-term outcomes have been reported from RCTs to date. The Working Group was unanimous in their opinion that patients would also value both long-and short-term outcomes, although patient input was not sought. Once these longer-term outcome data become more available, the emphasis on short-term outcomes may change.  The desirable effects (i.e., better short-term outcomes such as blood loss, time to first flatus, length of hospital stay, post-operative complications, hospital mortality rates) are large. At the same time, the undesirable effects (longer surgical times) are manageable in this population with adequate surgeon training in laparoscopic procedures. The Working Group believed the desirable effect (better short -term surgical outcomes) is large relative to the undesirable effects (longer surgical times). Once these longer-term outcome data become more available, the emphasis on shortterm outcomes may change.  The evidence is generalizable to the entire gastric cancer population as defined in this guidance document. 

# IMPLEMENTATION CONSIDERATIONS
The Working Group considered the recommendations provided above to be the ideal standard of care and would be feasible to implement. Furthermore, they may improve current health inequities by ensuring the same standards of care for all patients no matter where they are treated in Ontario. Thus, there is the potential for better outcomes for gastric cancer patients across the province. To support in this endeavour it would be useful if hospital mortality rates for gastric cancer surgery were available to hospitals as they are for other types of surgeries such as pancreas, lung, and esophagus. These recommendations may change current practice as many patients are currently only receiving a D1 LND even when a D2 is more appropriate. Moreover, laparoscopic surgeries may occur more often as time goes on and more surgeons are adequately trained in these procedures. These recommendations may come with no additional costs. In fact, overall costs may decrease owing to fewer recurrences, possibly fewer unnecessary surgeries, and reduced length of hospital stays as the number of laparoscopic surgeries performed increases. The Working Group believed the outcomes valued in this guideline would align well with patient values and patients would view these recommendations as acceptable. Disclaimer Care has been taken in the preparation of the information contained in this report. Nevertheless, any person seeking to consult the report or apply its recommendations is expected to use independent medical judgment in the context of individual clinical circumstances or to seek out the supervision of a qualified clinician. Cancer Care Ontario makes no representations or guarantees of any kind whatsoever regarding the report content or its use or application and disclaims any responsibility for its application or use in any way. 

# RELATED GUIDELINES

# VI. Implementation and Dissemination
The value of guidelines truly lies in their implementation and use. For that purpose, consideration was given to implementation during the drafting of this guideline document.

# CancerCare Resources
It was recognized that resources would be needed to distribute these guidelines to the community. For that purpose, the guideline will be accessible online through the CancerCare Manitoba website. Online availability will be preceded by an e-blast notification with the website embedded. Announcement of the guideline and updates will be through established provincial communication channels: Community Oncology Program to CCPN rural sites, UPCON clinics and WRHA Community Oncology Program sites. Use of the guideline in clinic will be through the online version.

# Educational Events
The guideline's recommendations were presented at Disease Site Group Meetings and the Cancer Surgery Update (2019).

# Concordance Measurement and Performance Audit
A plan is being developed regarding the guideline concordance measurement and will be presented to the CCMB standards committee for approval. Briefly, a panel will review each gastric cancer case at CCMB and provide a confidential feedback form covering the key recommendations to the treating physicians/surgeons. Suggestions will be presented in an encouraging format. The audit and feedback process will be done under the auspices of the CCMB standards committee, and include the protections therein. This plan will be finalized and implemented after the settling of the Covid-19 pandemic. 

# VIII. Conflicts of Interest
In accordance with the CCMB policy no. 01.001, "Conflict of Interest", the authors of this guideline disclosed no conflicts of interest and declares that no commercial support was received during the development of this guideline.