Endoscopic Stenting for Malignant Dysphagia in Patients with Esophageal Cancer
Tiuri Kroese
Round 1
Reviewer 1 Report
The management of malignant dysphagia in patients with esophageal cancer is a complex challenge, and endoscopic stenting has emerged as a potential solution for the relief of dysphagia caused by malignant strictures. However, several controversies persist regarding the use of esophageal stenting as a treatment option. This comprehensive review aims to provide a detailed analysis of the existing evidence and shed light on the various aspects associated with the use of stenting in the management of malignant dysphagia.
One of the key controversies surrounding esophageal stenting is its superiority compared to radiotherapy. While both modalities have shown efficacy in relieving dysphagia, the review highlights that stenting may have some disadvantages in terms of pain relief and the risk of adverse events compared to radiotherapy. This finding underscores the importance of carefully considering individual patient factors and preferences when selecting the appropriate treatment approach.
The timing of stenting in relation to radiotherapy and chemotherapy is another area of debate. The review points out that the risk of stent-related adverse events is significantly associated with prior radiotherapy, particularly when a radiation dose of >40 Gy is delivered to the esophagus after stenting. However, perforation is not associated with prior chemotherapy or additional chemotherapy after stenting. These findings emphasize the need for careful evaluation and individualized decision-making regarding the sequencing of treatments to optimize patient outcomes.
Furthermore, the review explores the safety considerations of different types of stents. Low-radial-force stents are suggested as a potential option to reduce the risk of adverse events, especially in patients with prior radiotherapy. This finding highlights the importance of selecting stent types based on individual patient characteristics and treatment history.
Despite the aforementioned controversies and limitations, the review emphasizes that stenting remains an important palliative option for patients with a short life expectancy and a strong desire for oral intake. It offers the advantage of faster improvement of dysphagia compared to radiotherapy or gastrostomy. However, the review also acknowledges that stenting may not provide the same level of long-term survival benefits as other treatment modalities, such as gastrostomy.
In conclusion, this comprehensive review provides valuable insights into the controversies surrounding the use of esophageal stenting for malignant dysphagia. It highlights the potential disadvantages of stenting in terms of pain relief, risk of adverse events, and survival outcomes compared to alternative treatments
Author Response
I would like to thank the reviewer for the valuable comments.
Reviewer 2 Report
This is a well written review article as to endoscopic stenting for malignant dysphagia in patients with advanced esophageal cancer. The findings and problems related to endoscopic stenting to date are clearly stated, and future issues are also well described.
The points to be worried about are the following minor points.
The author mentioned a comparison between stenting and gastrostomy. I may be straying from the topic, but is there a comparison between stenting and gastrostomy parenteral nutrition?
The author presents a summary of complications in the table 1 and 2, but could you elaborate on the breakdown such as table 3? Please provide at least the most frequent items and perforation frequencies. What was the grade of the complication.
Author Response
I would like to thank the reviewer for the valuable comments.
Comment 1: The author mentioned a comparison between stenting and gastrostomy. I may be straying from the topic, but is there a comparison between stenting and gastrostomy parenteral nutrition?
Reply 1: Unfortunately, no systematic reviews of the guidelines to date have identified articles comparing stenting and parenteral nutrition.
Comment 2: The author presents a summary of complications in the table 1 and 2, but could you elaborate on the breakdown such as table 3? Please provide at least the most frequent items and perforation frequencies. What was the grade of the complication.
Reply 2: In accordance with the reviewer’s suggestion, I have added the frequency of adverse events to the tables. The grades of the adverse events were not described in most articles.
Reviewer 3 Report
This is a review article that presents the data for stenting vs. RT for palliation of dysphagia. It also focuses on the complications of stent placement after RT and chemo as well as any risk/benefit for RT or chemo following stent placement.
My comments:
1. The randomized study by Penniment et al. should be criticized for the fact that the investigators did not administer palliative chemotherapy in their study outside of the RT or CRT. This is reflected in the dismal median OS in both groups (<7 months). I don’t think we can conclude from this flawed study that CRT is not superior to RT in a contemporary patient population treated with standard-of-care palliative chemotherapy
2. Are there data on the need for stent removal because of intolerance/pain or migration in any of the studies? If so, this should be included as it provides an important perspective about the disadvantages of stent placement. My anecdotal experience is that up to 20% of patients do not tolerate stent placement. They either require narcotics for pain relief and/or stent removal
3. I think this review article would greatly benefit from a discussion regarding the dysphagia improvement associated with 1st-line palliative chemotherapy, which is estimated to be up to 70-80%. As such, initiating palliative chemotherapy for patients with stage IV disease who remain able to tolerate a soft diet may be more beneficial than stenting or RT.
4. Similarly, issues to consider in choosing between RT vs. stenting is whether Pts are a candidate for palliative chemotherapy, what line of chemotherapy they are receiving and the extent of metastatic disease. For example, a patient with widespread metastatic disease who is chemotherapy-naïve may benefit more from either chemotherapy or stent placement. RT would delay the initiation of chemotherapy, which can effectively palliate the dysphagia and treat the extensive metastatic disease. On the other hand, a patient who has experienced disease progression on 2 prior lines of chemotherapy (and is therefore unlikely to derive much improvement in dysphagia with more systemic treatment) but has small-volume metastatic disease could be considered for either stenting or RT.
5. One important consider is that ramucirumab (alone or with paclitaxel) is considered standard 2nd-line therapy in Japan and the US. As this is an anti-angiogenic drug that is associated with a low risk of intestinal perforation, consideration needs to be given to the timing of stenting relative to ramucirumab-based therapy
6. Ultimately, I think this review would also be significantly strengthened if the Author provides his own recommendation regarding when to consider a stent vs. RT. The actual data that are available are not strong so an expert perspective would be highly valuable. Otherwise, this is just a recitation of studies.
7. In the Conclusions, “ED-induced (sic)” seems to be an incorrect term
English is fine
Author Response
I would like to thank the reviewer for the valuable comments.
Comment 1: The randomized study by Penniment et al. should be criticized for the fact that the investigators did not administer palliative chemotherapy in their study outside of the RT or CRT. This is reflected in the dismal median OS in both groups (<7 months). I don’t think we can conclude from this flawed study that CRT is not superior to RT in a contemporary patient population treated with standard-of-care palliative chemotherapy.
Reply 1: I understand the criticism regarding the results of study by Penniment et al. I have therefore added the following sentence to the section titled “3. Stenting and radiation as palliation of malignant dysphagia.”
“Because CRT is considered to be superior to RT in many situations, further studies are required to confirm the efficacy of CRT for palliation of malignant dysphagia.”
Comment 2: Are there data on the need for stent removal because of intolerance/pain or migration in any of the studies? If so, this should be included as it provides an important perspective about the disadvantages of stent placement. My anecdotal experience is that up to 20% of patients do not tolerate stent placement. They either require narcotics for pain relief and/or stent removal.
Reply 2: In accordance with the reviewer’s suggestion, I have added the following stent removal data from a prospective study to the section titled “7. Stent type and efficacy.”
“Stent removal was required in 4 of 97 patients. The reasons for self-expandable metallic stent removal were intolerable pain (n = 2), symptomatic tracheal compression (n = 1), and insufficient symptom relief (n = 1).”
Comment 3. I think this review article would greatly benefit from a discussion regarding the dysphagia improvement associated with 1st-line palliative chemotherapy, which is estimated to be up to 70-80%. As such, initiating palliative chemotherapy for patients with stage IV disease who remain able to tolerate a soft diet may be more beneficial than stenting or RT.
Reply 3: I thank the reviewer for this very important comment. In accordance with the reviewer’s suggestion, I have added a discussion regarding the dysphagia improvement associated with palliative chemotherapy in the section titled “8. Other topics.”
“8. Other topics
Systemic chemotherapy is usually recommended for patients with cStage IVB esophageal cancer. Previous studies have shown that systemic therapy results in dysphagia improvement in 72% to 90% of patients 2 to 6 weeks after initiation of therapy. The dysphagia relief can last from a few weeks to a few months or longer if the patient continues to respond to the therapy [43,44]. A Cochrane review on systemic therapy for esophageal cancer concluded that systemic therapy improves dysphagia; conversely, the authors recommended against using chemotherapy alone for dysphagia palliation in patients with esophageal cancer because of the high incidence of recurrent symptoms [45]. However, chemotherapy is evolving with the addition of immunotherapy, and the treatment outcomes of dysphagia palliation are expected to improve [46-48].
There are many options for the treatment of malignant dysphagia in patients with esophageal cancer. Development of a proper treatment strategy is important. For example, a chemotherapy-naïve patient with widespread metastatic disease may benefit more from chemotherapy. By contrast, a patient who has experienced disease progression on two or more lines of chemotherapy but has small-volume metastatic disease could benefit more from stenting or RT.”
Comment 4. Similarly, issues to consider in choosing between RT vs. stenting is whether Pts are a candidate for palliative chemotherapy, what line of chemotherapy they are receiving and the extent of metastatic disease. For example, a patient with widespread metastatic disease who is chemotherapy-naïve may benefit more from either chemotherapy or stent placement. RT would delay the initiation of chemotherapy, which can effectively palliate the dysphagia and treat the extensive metastatic disease. On the other hand, a patient who has experienced disease progression on 2 prior lines of chemotherapy (and is therefore unlikely to derive much improvement in dysphagia with more systemic treatment) but has small-volume metastatic disease could be considered for either stenting or RT.
Reply 4: In accordance with the reviewer’s suggestion, I have added comments regarding the effective use of chemotherapy, radiation, and stenting in the section titled 8. Other topics.”
“There are many options for the treatment of malignant dysphagia in patients with esophageal cancer. Development of a proper treatment strategy is important. For example, a chemotherapy-naïve patient with widespread metastatic disease may benefit more from chemotherapy. By contrast, a patient who has experienced disease progression on two or more lines of chemotherapy but has small-volume metastatic disease could benefit more from stenting or RT.”
Comment 5: One important consider is that ramucirumab (alone or with paclitaxel) is considered standard 2nd-line therapy in Japan and the US. As this is an anti-angiogenic drug that is associated with a low risk of intestinal perforation, consideration needs to be given to the timing of stenting relative to ramucirumab-based therapy.
Reply 5: Ramucirumab is not approved in Japan for the treatment of esophageal cancer (it is only approved for gastric cancer). I searched PubMed using the terms “stent,” “ramucirumab,” and “esophagus” but found only one short article. Therefore, I am very hesitant to comment on this issue because I have no experience in stenting patients treated with ramucirumab in Japan and the available data on this topic are limited.
Comment 6. Ultimately, I think this review would also be significantly strengthened if the Author provides his own recommendation regarding when to consider a stent vs. RT. The actual data that are available are not strong so an expert perspective would be highly valuable. Otherwise, this is just a recitation of studies.
Reply 6: I thank the reviewer for this very important comment. In accordance with the reviewer’s suggestion, I have added my own recommendations to the section titled “9. Conclusions.”
“Based on the evidence gathered to date and the author’s personal experience, the following three strategies are recommended. First, for patients with a good general condition and mild dysphagia (able to eat a liquid diet or soft diet), systemic chemotherapy is recommended. Second, for patients with a good general condition and severe dysphagia (unable to eat a liquid diet), CRT or RT is recommended. Although a previous study [8] failed to show the superiority of CRT for dysphagia relief, the author usually prefers CRT for patients who can tolerate CRT or patients who have extensive metastasis because the efficacy of CRT is usually higher than that of RT. Third, for patients with a poor general condition, the author recommends stenting because it can achieve rapid improvement of dysphagia.”
Comment 7: In the Conclusions, “ED-induced (sic)” seems to be an incorrect term.
Reply 7: Thank you for pointing out this typographical error. I have corrected this term to “esophageal cancer-induced dysphagia.”
Reviewer 4 Report
Thank you for this paper
I have some questions and comments:
1) please explain further about the reasons behind stenting vs. gastrostomy pros/cons. I think that would further strengthen the review.
2) Please explain further the low radial force stent vs. high radial force stent, and how we would know as clinicians which one those are.
3) The conclusion and main finding has to be better worded. What are you recommending in the end? BE more specific on if stenting is good for PALLIATIVE treatment and what your thoughts are on using stenting for curataive intent prior to esophagectomy, that would strengthen the review.
Thank you
editing needed for english
Author Response
I would like to thank the reviewer for the valuable comments.
Comment 1: Please explain further about the reasons behind stenting vs. gastrostomy pros/cons. I think that would further strengthen the review.
Reply 1: In accordance with the reviewer’s comment, I have added the following sentences to the section titled “4. Stenting and gastrostomy as palliation of malignant dysphagia.”
“The advantages of stenting are rapid relief of dysphagia and satisfaction derived from the ability to eat, whereas the disadvantages are adverse events such as chest pain, migration, mediastinitis, perforation, and bleeding. The advantages of gastrostomy are a stable nutritional status and safety of the procedure, whereas the disadvantages are dissatisfaction with the inability to eat and esophageal obstruction-related symptoms such as reflux of saliva. These treatment characteristics should be taken into consideration when a strategy is selected. “
Comment 2: Please explain further the low radial force stent vs. high radial force stent, and how we would know as clinicians which one those are.
Reply 2: In accordance with the reviewer’s comment, I have added several sentences to explain the radial force and axial force of stents and have cited an article in which the radial force of various stents was evaluated. This information has been added to the section titled “3. Stenting and radiation as palliation of malignant dysphagia.”
“In addition to the stent covering and the anti-reflux valve, the axial and radial forces of the stent are major determinants of the stent’s properties [33]. The radial force is the force that stents exert as they resist compression by the pressure of the esophageal wall; it is also the force that stents exert on the lumen as they expand to their original nominal diameter. The axial force is the force exerted on the luminal wall when the stent is in a curved position. The radial and axial forces of various stents were evaluated using an in vitro testing model [33].”
Comment 3: The conclusion and main finding has to be better worded. What are you recommending in the end? BE more specific on if stenting is good for PALLIATIVE treatment and what your thoughts are on using stenting for curative intent prior to esophagectomy, that would strengthen the review.
Reply 3: I thank the reviewer for this very important advice. In accordance with the reviewer’s suggestion, I have added my own recommendations to the section titled “9. Conclusions.”
“Based on the evidence gathered to date and the author’s personal experience, the following three strategies are recommended. First, for patients with a good general condition and mild dysphagia (able to eat a liquid diet or soft diet), systemic chemotherapy is recommended. Second, for patients with a good general condition and severe dysphagia (unable to eat a liquid diet), CRT or RT is recommended. Although a previous study [8] failed to show the superiority of CRT for dysphagia relief, the author usually prefers CRT for patients who can tolerate CRT or patients who have extensive metastasis because the efficacy of CRT is usually higher than that of RT. Third, for patients with a poor general condition, the author recommends stenting because it can achieve rapid improvement of dysphagia.”
Round 2
Reviewer 3 Report
I thank the Author for addressing my comments and queries. In particular, I find the manuscript much more authoritative and impactful now that the Author has provided his own professional opinion of how to consider the various treatment options for palliating dysphagia.
Minor editing is required
Reviewer 4 Report
thank you for your thoughtful revisions
Thank you
