Commentary: Opening a window when surgeons face awesome responses to immunotherapy
Bibliographic record
Abstract
Central MessageVarying tumor response patterns to immune checkpoint inhibitors have been observed. Some patients will benefit from aggressive, well-planned surgical excision and reconstruction.See Article page 329. Varying tumor response patterns to immune checkpoint inhibitors have been observed. Some patients will benefit from aggressive, well-planned surgical excision and reconstruction. See Article page 329. Immunotherapy has profoundly changed the paradigm in the treatment of several solid tumors over the past decade. In metastatic and locally advanced cutaneous squamous cell carcinomas not amenable to curative resection, immune checkpoint inhibition with cemiplimab have shown a 47% objective response rate.1Migden M.R. Rischin D. Schmults C.D. Guminski A. Hauschild A. Lewis K.D. et al.PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma.N Engl J Med. 2018; 379: 341-351Crossref PubMed Scopus (745) Google Scholar Another phase 2 open-label study including patients with locally advanced cutaneous squamous cell carcinoma, showed a 44% objective response rate with cemiplimab using the Response Evaluation Criteria in Solid Tumors version 1.1.2Migden M.R. Khushalani N.I. Chang A.L.S. Lewis K.D. Schmults C.D. Hernandez-Aya L. et al.Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial.Lancet Oncol. 2020; 21: 294-305Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar In many patients, the significant local response to immunotherapy and associated tumor shrinkage/contraction may change surgical planning. Some tumors considered nonamenable to curative resection, by the predicted impossibility of achieving a complete resection, patient-related clinical conditions, or the aggressiveness of the resection, have shown an impressive reduction after immunotherapy leading to a reconsideration of aggressive surgical excision. We enthusiastically enjoyed the report by Choi and colleagues,3Choi J.J. Allen R.J. Bains M.S. Cohen M.A. Yu Y. Elmadhun N. et al.Complex chest wall surgery to prevent vascular complications after immunotherapy and radiation treatment.J Thorac Cardiovasc Surg Tech. 2020; 4: 329-331Google Scholar which describes the successful resection of a large cutaneous squamous cell carcinoma with chest wall and thoracic inlet invasion. Notably, after 2 cycles of cemiplimab and 1 cycle of radiotherapy, the tumor underwent a significant superficial contraction with associated new bone erosion and close contact with the subclavian vessels. The decision for aggressive resection was justified to prevent potential catastrophic bleeding. Image-based tumor burden evaluation in patients receiving immunotherapy is sometimes challenging because the tumors can exhibit many patterns of response after delivery of treatment. Pseudoprogression and dissociated responses have been observed in many solid tumors after immunotherapy and are associated with better survival than true progression. However, tumor growth or the development of new lesions can be observed in these scenarios. Especially in cases of dissociated responses, a window for surgical treatment may open and must not be neglected. The decision to continue delivery of a drug versus proceed with aggressive surgical excision must be taken individually with consideration of the clinical features and the possibility of achieving complete resection. Biomarkers such as circulating tumor DNA4Cabel L. Proudhon C. Romano E. Girard N. Lantz O. Stern M.H. et al.Clinical potential of circulating tumour DNA in patients receiving anticancer immunotherapy.Nat Rev Clin Oncol. 2018; 15: 639-650Crossref PubMed Scopus (125) Google Scholar and chromosomal instability quantification of cell-free DNA5Weiss G.J. Beck J. Braun D.P. Bornemann-Kolatzki K. Barilla H. Cubello R. et al.Tumor cell-free DNA copy number instability predicts therapeutic response to immunotherapy.Clin Cancer Res. 2017; 23: 5074-5081Crossref PubMed Scopus (98) Google Scholar are showing encouraging accuracy in evaluating response to immunotherapy and might be another useful tool in surgical decision making in the near future. In the case presented by Choi and colleagues3Choi J.J. Allen R.J. Bains M.S. Cohen M.A. Yu Y. Elmadhun N. et al.Complex chest wall surgery to prevent vascular complications after immunotherapy and radiation treatment.J Thorac Cardiovasc Surg Tech. 2020; 4: 329-331Google Scholar the decision to proceed with resection of such a large tumor was accompanied by the need to reconstruct the chest wall. Acellular collagen matrix patches combine rigidity and durability needed for chest stabilization, along with easy handling and strength for suture fixation. It also allows a remodeling process with tissue integration and neovascularization, which may reduce infection risk and help with healing.6Schmidt J. Redwan B. Koesek V. Heitplatz B. Bedetti B. Aebert H. et al.Thoracic wall reconstruction with acellular porcine dermal collagen matrix.J Thorac Cardiovasc Surg. 2016; 64: 245-251Google Scholar Because the chest wall offers significant stretch, the collagen matrix's tissue origin must be considered when selecting the prosthesis, due to the fact that the porcine origin matrix apparently offers more stretch resistance than those from humans. Prosthetic patches must always be covered with well-vascularized tissue flaps, preferentially muscle or omentum. We congratulate the authors for the surgical and oncological success in this complex case. Complex chest wall surgery to prevent vascular complications after immunotherapy and radiation treatmentJTCVS TechniquesVol. 4PreviewA 64-year-old woman with diabetes presented with extensive destruction of the right anterior chest wall and thoracic inlet. A computed tomographic scan of the chest showed a large necrotic mass (20 × 20 cm), with marked destruction of the right clavicle and focal destruction of the manubrium (Figure 1). Biopsy yielded poorly differentiated squamous cell carcinoma with unknown programmed death-ligand 1 status. The patient gave written informed consent for the publication of this case. Full-Text PDF Open Access
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".