Experiences and Hopes Among Patients with Colorectal Carcinoma and Peritoneal Metastases Who Are Participating in an Early-Phase Clinical Trial

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This study focuses on the experiences of patients with colorectal cancer (CRC) and peritoneal metastases who participated in an early-phase clinical trial in which the intraperitoneal α-emitting radiopharmaceutical Radspherin® was administered after CRS-HIPEC. Using semi-structured interviews and reflexive thematic analysis, the authors provide a patient-centered perspective on perioperative and follow-up needs, communication burden, and ongoing psychosocial challenges. The topic is clinically relevant and may help optimize informed communication, follow-up support, and patient-centered outcomes in early-phase trials.

Overall limitations: The sample size is small (n = 10) and drawn from a single center with a relatively homogeneous population. In addition, key methodological elements of qualitative research (researcher positionality/reflexivity, justification of adequacy via saturation or “information power,” coding procedures and strategies to ensure trustworthiness, ethics and data availability) should be reported more transparently and rigorously. Major revision is recommended.

Specific comments:

1. The authors justify the adequacy of n = 10 using the concept of “information power,” but this rationale requires more verifiable support. Please clarify whether not reaching the planned sample size of 15 could have resulted in missing perspectives from key subgroups (e.g., synchronous vs. metachronous PM, varying severity of complications, patients with recurrence/progression).

2. Participant recruitment and potential selection bias should be discussed more thoroughly. Patients willing to enroll in an early-phase trial may be inherently more optimistic and have higher trust in the clinical team, which could amplify positive perceptions and experiences.

3. In the second round of interviews, only three were conducted face-to-face while six were conducted by telephone. Please discuss whether the mode of interview (telephone vs. in-person) may have influenced the depth, nuance, or content of responses, and how this potential bias was addressed.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

1. The introduction focused on clinical outcomes. The authors are advised to add a stronger scientific rationale for using α-emitters.
2. Provide more background on colorectal carcinoma and peritoneal metastases. Authors can follow this article 2174/1871530320666200515115723 and include some part to enrich the introduction.
3. Add a paragraph explaining why α-particle radiation is effective for intraperitoneal disease.
4. Highlight the novelty and need for this qualitative study.
5. Provide a comprehensive description of the inclusion/exclusion criteria used for participant selection.
6. Authors can include the coding process in detail, including the software used and steps for theme generation.
7. Justify the use of two interview rounds.
8. Briefly explain the purpose of longitudinal interviews
9. Use either “patients” or “participants” consistently.
10. Reflexivity theory and qualitative rigor could be strengthened by citing established qualitative methodology references.
11. Include a thematic map or coding framework.
12. Provide examples of interview questions in a table format.
13. The authors are recommended to revise the entire manuscript as it requires intense grammatical corrections.

Author Response

Please see the attachment.

 

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

1. The sample size is very small with only 10 participants from a single center and a single cohort (2a), which makes it very difficult to make a generalized decision.
2. There is no clinical perspectives, observation note, the whole study relies on the patient self reported data. Lack of clinical notes weaken the arguments.
3. As per the manuscript, Author mentioned that patients have underwent both CRS-HIPEC and Radspherin. This is unclear which drug has made the intervention during self reported interview.
4. There is a reported case of side effects with a possible radiation-related bowel complication and contrast alpha and beta-emitting agents. It is not clear how this case reflects together with historical toxicity data relates/influence other patient risk.
5. The paper lacks discussion on how codes were grouped into themes or how, if any, disagreements between analysts were resolved. More details methodology is needed.

 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

1. Sample Size and Generalizability
While the qualitative design provides valuable insights into patient experiences, the small sample size (n=10) from a single institution limits the transferability of findings. Although the authors cite "information power" to justify the sample, the lack of demographic diversity (all participants were of white Western ethnicity) and potential survivorship bias (one participant died before the second interview) should be explicitly addressed. Consider expanding the discussion on how these limitations affect the interpretation of themes and their applicability to broader populations, particularly in multicultural or resource-limited settings.

2. Reflexivity and Potential Bias
The recruitment process involved the principal investigator (PI) of the clinical trial, raising concerns about social desirability bias. Participants may have felt obliged to provide favorable feedback due to loyalty or gratitude toward their treating clinicians. While the first author’s independence from clinical care is noted, the manuscript would benefit from a deeper reflexive analysis of how the researchers’ roles (e.g., PI involvement) might have influenced participant responses. A subsection on mitigating strategies for such biases would strengthen methodological rigor.

3. Ethical and Safety Considerations
The manuscript mentions that none of the participants attributed adverse events to Radspherin®. However, one patient (P10) experienced a bowel perforation 72 days post-treatment, a known rare complication of CRS-HIPEC. The authors dismiss Radspherin®’s role due to the short range of α-particles but should provide radiation-specific toxicity data from preclinical or prior clinical studies to support this claim. Additionally, clarify whether adverse event attribution was systematically assessed (e.g., via causality algorithms) or solely based on patient perception.

4. Integration of Clinical Context
The discussion would benefit from a more robust integration of clinical trial phases (phase 1/2a) and their implications for patient expectations. Early-phase trials prioritize safety and dosing, yet participants perceived Radspherin® as a therapeutic opportunity. Address this discrepancy by discussing how hope and therapeutic misconception are common in early-phase oncology trials and suggest strategies to balance optimism with realistic communication in future studies.

5. Follow-Up and Long-Term Outcomes
The study highlights unmet needs in long-term follow-up, particularly regarding Radspherin®-specific communication. However, the second interviews occurred 10–12 months post-treatment, which may not fully capture late effects or evolving perspectives. Provide rationale for this timeframe and discuss whether a longer follow-up period (e.g., 24 months) would enhance understanding of survivorship challenges. Additionally, include recommendations for structured psychosocial support pathways in the "Clinical Implications" section to address persistent functional and emotional burdens.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

All questions were addressed.