The principle of salvage in the context of COVID-19.

The prioritisation of scarce resources has a particular urgency within the context of the COVID-19 pandemic crisis. This paper sets out a hypothetical case of Patient X (who is a nurse) and Patient Y (who is a non-health care worker). They are both in need of a ventilator due to COVID-19 with the same clinical situation and expected outcomes. However, there is only one ventilator available. In addressing the question of who should get priority, the proposal is made that the answer may lie in how the pandemic is metaphorically described using military terms. If nursing is understood to take place at the 'frontline' in the 'battle' against COVID-19, a principle of military medical ethics-namely the principle of salvage-can offer guidance on how to prioritise access to a life-saving resource in such a situation. This principle of salvage purports a moral direction to return wounded soldiers back to duty on the battlefield. Applying this principle to the hypothetical case, this paper proposes that Patient X (who is a nurse) should get priority of access to the ventilator so that he/she can return to the 'frontline' in the fight against COVID-19.

Outcomes in patients with aggressive B-cell non-Hodgkin lymphoma after intensive frontline treatment failure.

BACKGROUND: Salvage immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation is the standard-of-care second-line treatment for patients with relapsed/refractory diffuse large B-cell lymphoma after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Outcomes after receipt of second-line immunochemotherapy in patients with aggressive B-cell lymphomas who relapse or are refractory to intensive first-line immunochemotherapy regimens (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab [R-EPOCH], rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine [R-HyperCVAD], rituximab, cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate alternating with ifosfamide, etoposide, and cytarabine [R-CODOX-M/IVAC]) remain unknown. METHODS: Outcomes of patients with non-Burkitt, aggressive B-cell lymphomas and relapsed/refractory disease after first-line treatment with intensive immunochemotherapy regimens who received platinum-based second-line immunochemotherapy were reviewed retrospectively. Analyses were performed to determine progression-free survival (PFS) and overall survival (OS) from the time of receipt of second-line immunochemotherapy. RESULTS: In total, 195 patients from 19 academic centers were included in the study. The overall response rate to second-line immunochemotherapy was 44%, with a median PFS of 3 months and a median OS of 8 months. Patients with early treatment failure (primary refractory or relapse <12 months from completion of first-line therapy) experienced inferior median PFS (2.8 vs 23 months; P < .001) and OS (6 months vs not reached; P < .001) compared with patients with late treatment failure. Although the 17% of patients with early failure who achieved a complete response to second-line immunochemotherapy experienced prolonged survival, this outcome could not be predicted by clinicopathologic features at the start of second-line immunochemotherapy. CONCLUSIONS: Patients with early treatment failure after intensive first-line immunochemotherapy experience poor outcomes after receiving standard second-line immunochemotherapy. The use of standard-of-care or experimental therapies currently available in the third-line setting and beyond should be investigated in the second-line setting for these patients.

Adjuvant and Salvage Radiotherapy after Prostatectomy: ASTRO/AUA Guideline Amendment 2018-2019.

PURPOSE: The purpose of this amendment is to incorporate newly-published literature into the original ASTRO/AUA Adjuvant and Salvage Radiotherapy after Prostatectomy Guideline and to provide an updated clinical framework for clinicians. MATERIALS AND METHODS: The original systematic review yielded 294 studies published between January 1990 and December 2012. In April 2018, the guideline underwent an amendment and incorporated 155 references that were published from January 1990 through December 2017. Two new key questions were added. One on the use of genomic classifiers and the other on the treatment of oligo-metastases with radiation post-radical prostatectomy. RESULTS: A new statement on the use of hormone therapy with salvage radiotherapy after radical prostatectomy was added and long-term data was used to update an existing statement on adjuvant radiotherapy. The balance of the guideline statements were re-affirmed and references were added to the existing literature base. A discussion on the use of genomic classifiers as a risk stratification tool was added to the future research discussion. No relevant data on oligo-metastases was found. CONCLUSIONS: Hormone therapy should be offered to patients who have had radical prostatectomy and who are candidates for salvage radiotherapy. The clinician should discuss possible short- and long-term side effects with the patient as well as the potential benefits of preventing recurrence. The decision to use hormone therapy should be made by the patient and a multi-disciplinary team of providers with full consideration of the patient's history, values, preferences, quality of life, and functional status.

ESMO Consensus Conference on testicular germ cell cancer: diagnosis, treatment and follow-up.

The European Society for Medical Oncology (ESMO) consensus conference on testicular cancer was held on 3-5 November 2016 in Paris, France. The conference included a multidisciplinary panel of 36 leading experts in the diagnosis and treatment of testicular cancer (34 panel members attended the conference; an additional two panel members [CB and K-PD] participated in all preparatory work and subsequent manuscript development). The aim of the conference was to develop detailed recommendations on topics relating to testicular cancer that are not covered in detail in the current ESMO Clinical Practice Guidelines (CPGs) and where the available level of evidence is insufficient. The main topics identified for discussion related to: (1) diagnostic work-up and patient assessment; (2) stage I disease; (3) stage II-III disease; (4) post-chemotherapy surgery, salvage chemotherapy, salvage and desperation surgery and special topics; and (5) survivorship and follow-up schemes. The experts addressed questions relating to one of the five topics within five working groups. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel. A consensus vote was obtained following whole-panel discussions, and the consensus recommendations were then further developed in post-meeting discussions in written form. This manuscript presents the results of the expert panel discussions, including the consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.

ACR Appropriateness Criteria® Adjuvant Management of Early-Stage Endometrial Cancer.

These consensus guidelines on adjuvant radiotherapy for early-stage endometrial cancer were developed from an expert panel convened by the American College of Radiology. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method; and Grading of Recommendations Assessment, Development, and Evaluation, or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. After a review of the published literature, the panel voted on three variants to establish best practices for the utilization of imaging, radiotherapy, and chemotherapy after primary surgery for early-stage endometrial cancer.

Comparison of methods for estimating the effect of salvage therapy in prostate cancer when treatment is given by indication.

For patients who were previously treated for prostate cancer, salvage hormone therapy is frequently given when the longitudinal marker prostate-specific antigen begins to rise during follow-up. Because the treatment is given by indication, estimating the effect of the hormone therapy is challenging. In a previous paper we described two methods for estimating the treatment effect, called two-stage and sequential stratification. The two-stage method involved modeling the longitudinal and survival data. The sequential stratification method involves contrasts within matched sets of people, where each matched set includes people who did and did not receive hormone therapy. In this paper, we evaluate the properties of these two methods and compare and contrast them with the marginal structural model methodology. The marginal structural model methodology involves a weighted survival analysis, where the weights are derived from models for the time of hormone therapy. We highlight the different conditional and marginal interpretations of the quantities being estimated by the three methods. Using simulations that mimic the prostate cancer setting, we evaluate bias, efficiency, and accuracy of estimated standard errors and robustness to modeling assumptions. The results show differences between the methods in terms of the quantities being estimated and in efficiency. We also demonstrate how the results of a randomized trial of salvage hormone therapy are strongly influenced by the design of the study and discuss how the findings from using the three methodologies can be used to infer the results of a trial.

Quantification of myocardial salvage by myocardial perfusion SPECT and cardiac magnetic resonance--reference standards for ECG development.

In order to determine the cardioprotective efficacy of acute reperfusion therapy, assessed as myocardial salvage, in patients with acute coronary occlusion, the final myocardial infarct (MI) size needs to be related to the amount of ischemic myocardium during coronary occlusion, referred to as the myocardium at risk (MaR). There are currently several imaging approaches available for quantification of both MI size and MaR in vivo of which some have been validated both in pre-clinical and clinical settings. These methods often involve the use of either myocardial perfusion SPECT or cardiac magnetic resonance (CMR). These imaging methods could potentially be used to further develop and validate ECG methods for determination of MI size and MaR. Therefore, the aim of the present review is to give an overview of myocardial perfusion SPECT and CMR methods available for assessment of myocardial salvage by determination of MI size and MaR.

Classical Hodgkin's lymphoma: the Lymphoma Study Association guidelines for relapsed and refractory adult patients eligible for transplant.

The Hodgkin's Lymphoma Committee of the Lymphoma Study Association (LYSA) gathered in 2012 to prepare guidelines on the management of transplant-eligible patients with relapsing or refractory Hodgkin's lymphoma. The working group is made up of a multidisciplinary panel of experts with a significant background in Hodgkin's lymphoma. Each member of the panel of experts provided an interpretation of the evidence and a systematic approach to obtain consensus was used. Grades of recommendation were not required since levels of evidence are mainly based on phase II trials or standard practice. Data arising from randomized trials are emphasized. The final version was endorsed by the scientific council of the LYSA. The expert panel recommends a risk-adapted strategy (conventional treatment, or single/double transplantation and/or radiotherapy) based on three risk factors at progression (primary refractory disease, remission duration < 1 year, stage III/IV), and an early evaluation of salvage chemosensitivity, including (18)fluorodeoxy glucose-positron emission tomography interpreted according to the Deauville scoring system. Most relapsed or refractory Hodgkin's lymphoma patients chemosensitive to salvage should receive high-dose therapy and autologous stem-cell transplantation as standard. Efforts should be made to increase the proportion of chemosensitive patients by alternating non-cross-resistant chemotherapy lines or exploring the role of novel drugs.

Outcome of salvage surgery for anal squamous cell carcinoma.

AIM: The purpose of this study was to examine factors related to treatment failure following chemoradiotherapy for squamous cancer and to compare the outcome of salvage surgery in one unit with national audit standards published by the Association of Coloproctology of Great Britain and Ireland (ACPGBI) (ACPGBI position statement for management of anal cancer. Colorectal Disease 2011; 13(Suppl. 1): 1-52). METHOD: Patients with squamous cell carcinoma of the anus treated with radical intent between 1997 and 2010 in a single tertiary referral oncology institute were prospectively identified. Multivariate analysis was used to establish factors associated with treatment failure. Cancer-specific end-points after salvage surgery were determined by Kaplan-Meier survival analysis. RESULTS: Ninety-five patients received chemoradiotherapy with radical intent with a 5-year overall survival of 83% (all stages) at a median follow up of 35 months. Of these, 11 (12%) required salvage surgery, five of whom were Stage T4 at presentation. Six patients had failed to respond to chemoradiotherapy and five presented with recurrence at a median of 10 (10-36) months. Only Stage T4 disease at presentation was predictive of the need for salvage surgery (OR 5.6, CI 4.9-6.3, P = 0.015). There was no surgical mortality and no delayed perineal healing where a myocutaneous flap was used. The resection margin was involved in one (9%) patient. The 5-year survival rate was 64%. Audit standards for case selection, local control, survival and perineal complications were achieved. CONCLUSION: Long-term survival was achieved in two- thirds of patients following salvage surgery after failed primary chemoradiotherapy for anal cancer in a multidisciplinary oncological unit. Stage T4 disease at presentation strongly predicted the need for subsequent salvage intervention.

Treatment of relapsed acute lymphoblastic leukemia: approaches used by pediatric oncologists and bone marrow transplant physicians.

BACKGROUND: Management of relapsed B-precursor acute lymphoblastic leukemia (ALL) is challenging and varied. We hypothesized that treatment approaches differ between pediatric oncologists and bone marrow transplant (BMT) physicians. PROCEDURE: A survey addressing management of relapsed ALL was sent to pediatric oncologists (n = 883) and BMT (n = 86) physicians across North America. RESULTS: A number of similarities in treatment approaches were identified including: choice of chemotherapy for re-induction/consolidation, preference for unrelated donors (URDs) in very early marrow relapse and the choice to not use URD donors in late marrow relapse. However, differences between the two disciplines were noted. For patients who relapsed 18-36 months from diagnosis, the majority of oncologists (53.7%) would retreat with chemotherapy while a majority BMT physicians (70.3%) recommended URD transplant (P < 0.001). Oncologists were also less likely to use minimal residual disease (MRD) in relapse assessment compared to BMT physicians (52% vs. 67.2%; P = 0.028) and more oncologists believed MRD testing was experimental and/or not proven in relapsed ALL (27.1% vs. 12.3%; P = 0.011). CONCLUSIONS: This study highlights management differences in children with ALL between pediatric oncologists and BMT physicians, identifying opportunities for collaborative clinical trials.

Assessing the Best Surgical Template at Salvage Pelvic Lymph Node Dissection for Nodal Recurrence of Prostate Cancer After Radical Prostatectomy: When Can Bilateral Dissection be Omitted? Results from a Multi-institutional Series.

The best surgical template for salvage pelvic lymph node dissection (sLND) in patients with nodal recurrence from prostate cancer (PCa) after radical prostatectomy (RP) is currently unknown. We analyzed data of 189 patients with a unilateral positive positron emission tomography (PET) scan of the pelvic lymph node areas, who were treated with bilateral pelvic sLND after RP at 11 high-volume centers. The primary endpoint was missed contralateral disease at final pathology, defined as lymph node positive for PCa in the side opposite to the positive spot(s) at the PET scan. Overall, 93 (49%) and 96 (51%) patients received a 11C-choline and a 68Ga prostate-specific membrane antigen (PSMA) PET scan, respectively, and 171 (90%) and 18 (10%) men had one and two positive spots, respectively. The rate of missed contralateral PCa was 18% (34/189), with the rates being 17% (29/171) and 28% (5/18) in men with one and two positive spots, respectively. While the rate of contralateral disease did not differ between 68Ga-PSMA and 11C-choline (29% and 27%, respectively) among men with two positive spots, the rate of contralateral PCa was only 6% with 68Ga-PSMA versus 28% with 11C-choline in patients with a single positive spot. This finding was confirmed at multivariable logistic regression analysis predicting missed disease at final pathology after accounting for confounders (odds ratio: 0.24; p = 0.001). However, in men with a single positive spot at 68Ga-PSMA PET/computed tomography, the rate of single confirmed lymph node metastasis at final pathology was only 33%, suggesting the need for extended template even if unilateral dissection is performed. Awaiting confirmatory studies, patients diagnosed with a single positive spot at the 68Ga-PSMA PET scan might be considered for unilateral extended pelvic sLND. PATIENT SUMMARY: We assessed the risk of missing contralateral disease in patients with a positron emission tomography (PET) scan suggestive of unilateral nodal recurrence from prostate cancer (PCa) after radical prostatectomy and who were treated with bilateral salvage lymph node dissection (sLND). Variability exists according to the number of positive spots and PET tracer, with the lowest rate of missed PCa in men diagnosed with a single positive spot at a 68Ga prostate-specific membrane antigen PET scan (6%). If replicated, our data suggest that these patients might be considered for unilateral extended pelvic sLND.

Pathologically Node-Positive Prostate Cancer: Casting for Cure When the Die Is Cast?

The postoperative management of men with lymph node involved prostate cancer (pN+) remains a challenge as there is a general lack of randomized trial data and a range of management strategies. Retrospective studies suggest a variable clinic course for patients with pN+ prostate cancer. Some men progress rapidly to metastatic disease despite further therapies, whereas other men can have a period of prolonged quiescence without adjuvant androgen deprivation therapy (ADT) or radiation therapy (RT). For men who have undergone radical prostatectomy, randomized trial data indicate that the addition of ADT in pN+ disease extends metastasis-free, prostate cancer-specific, and overall survival. Additional retrospective studies suggest that adding RT is potentially beneficial in this setting, improving overall and cancer-specific survival especially in men with certain pathologic parameters. Conversely, men with lower disease burden in their lymph nodes have longer times to progression and may be candidates for observation and salvage therapy as opposed to adjuvant ADT/RT.

[The efficacy and safety of salvage surgery for local recurrent nasopharyngeal carcinoma: a systematic review and Meta-analysis].

Objective: To assess the current evidence regarding the efficacy, safety, and potential advantages of endoscopic compared with open salvage surgery for patients with local recurrent nasopharyngeal carcinoma. Methods: A systematic search of Pubmed/Medline, Embase, and Cochrane databases ranged between 2000 and 2017 was conducted. Included studies reported specific residual or local recurrent nasopharyngeal cancer survival data. Proportional Meta-analysis was performed on both outcomes with a random-effects model and the 95% confidential intervals were calculated by Stata 12.0 software. Results: A total of 24 case series studies were included in the Meta-analysis.The pooled 2-year overall survival rates of endoscopic and open group were 84% (95%CI:72%-93%), 68%(95%CI:59%-77%),respectively.The pooled 2-year disease-free survival rates of endoscopic and open group were 68%(95%CI:53%-81%), 65%(95%CI:54%-75%),respectively. The pooled 5-year overall survival rates of endoscopic and open group were 72%(95%CI:37%-97%), 48% (95%CI:40%-56%),respectively.The pooled 5-year disease-free survival rates of endoscopic and open group were 65%(95%CI:29%-93%), 50%(95%CI:43%-57%),respectively.The combined outcome of endoscopic was higher than open procedure. In addition, less severe complications, lower local recurrence rates(27%vs32%).The 2-year overall survival rates of endoscopic was higher than open procedure in the staging of rT1, rT2, and rT3 (93%vs87%; 77%vs63%; 67%vs53%) , but was equal to open in the staging for rT4 (35%vs35%) .Meta-regression showed that the heterogeneity was correlated with advanced tumor ratio. Conclusions: The present Meta-analysis reveals that endoscopic approach offers a safe and efficient alternative to open approach with better short-term outcome and fewer postoperative complications in selecting patients strictly.

Systematic Review and Meta-analysis: Optimal Salvage Therapy in Acute Severe Ulcerative Colitis.

BACKGROUND: Infliximab is an effective salvage therapy in acute severe ulcerative colitis; however, the optimal dosing strategy is unknown. We performed a systematic review and meta-analysis to examine the impact of infliximab dosage and intensification on colectomy-free survival in acute severe ulcerative colitis. METHODS: Studies reporting outcomes of hospitalized steroid-refractory acute severe ulcerative colitis treated with infliximab salvage were identified. Infliximab use was categorized by dose, dose number, and schedule. The primary outcome was colectomy-free survival at 3 months. Pooled proportions and odds ratios with 95% confidence intervals were reported. RESULTS: Forty-one cohorts (n = 2158 cases) were included. Overall colectomy-free survival with infliximab salvage was 79.7% (95% confidence interval [CI], 75.48% to 83.6%) at 3 months and 69.8% (95% CI, 65.7% to 73.7%) at 12 months. Colectomy-free survival at 3 months was superior with 5-mg/kg multiple (≥2) doses compared with single-dose induction (odds ratio [OR], 4.24; 95% CI, 2.44 to 7.36; P < 0.001). However, dose intensification with either high-dose or accelerated strategies was not significantly different to 5-mg/kg standard induction at 3 months (OR, 0.70; 95% CI, 0.39 to 1.27; P = 0.24) despite being utilized in patients with a significantly higher mean C-reactive protein and lower albumin levels. CONCLUSIONS: In acute severe ulcerative colitis, multiple 5-mg/kg infliximab doses are superior to single-dose salvage. Dose-intensified induction outcomes were not significantly different compared to standard induction and were more often used in patients with increased disease severity, which may have confounded the results. This meta-analysis highlights the marked variability in the management of infliximab salvage therapy and the need for further studies to determine the optimal dose strategy.