Oncological risks associated with the planned watch-and-wait strategy using total neoadjuvant treatment for rectal cancer: A narrative review.

Overall survival benefit of total neoadjuvant treatment (TNT) remains unconfirmed. Thus, in our opinion, the main rationale for using TNT is a planned watch-and-wait (w&w) strategy to improve patients' long-term quality of life through organ preservation. The OPRA randomized trial, which examined a planned w&w strategy using TNT, showed a higher organ preservation rate but also a higher regrowth rate compared to studies on the opportunistic w&w strategy. Higher rates of complete clinical response with TNT did not improve disease-free survival compared to historical controls. Therefore, the gain in organ-sparing capability might not be balanced by the increased oncological risk. The ultimate local failure rate in the intention-to-treat analysis of the OPRA trial was 13% for induction chemotherapy and 16% for consolidation chemotherapy, which seems higher than expected compared to 8% in a meta-analysis of w&w studies or 12% after TNT and surgery in the PRODIGE-23 and RAPIDO trials, which enrolled patients with more advanced cancers than the OPRA trial. Other studies also suggest worse local control when surgery is delayed for radio-chemoresistant cancers. Our review questions the safety of the planned w&w strategy using TNT in unselected patients. To reduce the oncological risk while maintaining high organ preservation rates, we suggest that the planned w&w strategy using TNT requires a two-tier patient selection process: before treatment and after tumor response assessment at the midpoint of consolidation chemotherapy. These robust selections should identify patients who are unlikely to achieve organ preservation with TNT and would be better managed by preoperative chemoradiotherapy (without consolidation chemotherapy) and surgery, or by discontinuing consolidation chemotherapy and proceeding directly to surgery.

The potential of virtual triage AI to improve early detection, care acuity alignment, and emergent care referral of life-threatening conditions.

Objective: To evaluate the extent to which patient-users reporting symptoms of five severe/acute conditions requiring emergency care to an AI-based virtual triage (VT) engine had no intention to get such care, and whose acuity perception was misaligned or decoupled from actual risk of life-threatening symptoms. Methods: A dataset of 3,022,882 VT interviews conducted over 16 months was evaluated to quantify and describe patient-users reporting symptoms of five potentially life-threatening conditions whose pre-triage healthcare intention was other than seeking urgent care, including myocardial infarction, stroke, asthma exacerbation, pneumonia, and pulmonary embolism. Results: Healthcare intent data was obtained for 12,101 VT patient-user interviews. Across all five conditions a weighted mean of 38.5% of individuals whose VT indicated a condition requiring emergency care had no pre-triage intent to consult a physician. Furthermore, 61.5% intending to possibly consult a physician had no intent to seek emergency medical care. After adjustment for 13% VT safety over-triage/referral to ED, a weighted mean of 33.5% of patient-users had no intent to seek professional care, and 53.5% had no intent to seek emergency care. Conclusion: AI-based VT may offer a vehicle for early detection and care acuity alignment of severe evolving pathology by engaging patients who believe their symptoms are not serious, and for accelerating care referral and delivery for life-threatening conditions where patient misunderstanding of risk, or indecision, causes care delay. A next step will be clinical confirmation that when decoupling of patient care intent from emergent care need occurs, VT can influence patient behavior to accelerate care engagement and/or emergency care dispatch and treatment to improve clinical outcomes.

Which tumour factors preclude organ preservation in patients with rectal cancer?

BACKGROUND: cT3cdT4, cN2, mesorectal nodes > 8 mm, clinically positive lateral nodes, extramural vascular invasion (EMVI) and mesorectal fascia threatening (MRF+) have been utilized as exclusion criteria in several studies on the watch-and-wait (w&w) strategy. Here, our aim was to validate these criteria through a post hoc analysis of two pooled prospective studies on w&w following routine radio(chemo)therapy. METHODS: A review of baseline magnetic resonance imaging was performed in a subgroup of 223 patients treated at a single institution. Of these, 17.9 % started w&w, 12.6 % achieved clinical complete response (cCR) and 9.0 % sustained cCR during median follow-up of 54 months. RESULTS: The multivariable logistic analysis showed that the proportion of circumferential bowel involvement and EMVI significantly influenced the chance of sustained cCR; odds ratios were 0.063 (95 % confidence interval [CI] 0.008-0.489, p = 0.008), and 0.109 (95 % CI 0.014-0.850, p = 0.034), respectively. Sustained cCR was observed in none of the 57 patients with 90 %-100 % circumferential bowel involvement and in only one of the 89 patients with EMVI. In contrast, cT3cdT4, cN2, mesorectal nodes > 8 mm, clinically positive lateral nodes or MRF+ were not independently associated with sustained cCR. Among the subgroups of patients with these features but without (near-)circular tumour or EMVI+, sustained cCR was observed in 12 %-25 % of patients. CONCLUSION: Sustained cCR after routine preoperative radio(chemo)therapy is unlikely in patients with (near-)circular tumour or EMVI, whereas patients with cT3cdT4, cN2, mesorectal nodes > 8 mm, clinically positive lateral nodes and MRF+ should not be denied w&w.

How Virtual Triage Can Improve Patient Experience and Satisfaction: A Narrative Review and Look Forward.

Objective: To complete a review of the literature on patient experience and satisfaction as relates to the potential for virtual triage (VT) or symptom checkers to enhance and enable improvements in these important health care delivery objectives. Methods: Review and synthesis of the literature on patient experience and satisfaction as informed by emerging evidence, indicating potential for VT to favorably impact these clinical care objectives and outcomes. Results/Conclusions: VT enhances potential clinical effectiveness through early detection and referral, can reduce avoidable care delivery due to late clinical presentation, and can divert primary care needs to more clinically appropriate outpatient settings rather than high-acuity emergency departments. Delivery of earlier and faster, more acuity level-appropriate care, as well as patient avoidance of excess care acuity (and associated cost), offer promise as contributors to improved patient experience and satisfaction. The application of digital triage as a front door to health care delivery organizations offers care engagement that can help reduce patient need to visit a medical facility for low-acuity conditions more suitable for self-care, thus avoiding unpleasant queues and reducing microbiological and other patient risks associated with visits to medical facilities. VT also offers an opportunity for providers to make patient health care experiences more personalized.

The ultimate local failure rate after the watch-and-wait strategy for rectal cancer: a systematic review of literature and meta-analysis.

BACKGROUND: We hypothesise that a high rate of tumour regrowth after the watch-and-wait (w&w) strategy may lead, despite salvage surgery, to a significant impairment of ultimate local control compared with immediate surgery. MATERIALS AND METHODS: To test this hypothesis, we conducted meta-analyses of studies on the w&w strategy (both opportunistic and planned) with an ultimate local failure rate as an endpoint in three patient groups: (1) in all starting radio(chemo)therapy as potential w&w candidates, (2) in a subgroup starting w&w, and (3) in a subgroup with regrowth. RESULTS: We identified eight studies for evaluation of local failure in group 1 (N = 837) and 36 studies in group 2 (N = 1914) and in group 3 (N = 439). The meta-analysis revealed an ultimate local failure rate of 8.0% (95% CI 4.8%-12.1%) in group 1 and 5.4% (95% CI 3.9%-7.1) in group 2. These rates are similar to those reported in the literature following preoperative chemoradiation and surgery. However, in the most unfavourable group 3 (with regrowth), the rate of ultimate local failure was 24.1% (95% CI 17.9%-30.9%), with the most common causes being patients' refusal of salvage total mesorectal excision (TME) (9.1%), recurrence after salvage TME (7.8%), distant metastases (4.1%), frailty (2.4%), and pelvic tumour unresectability (1.7%). CONCLUSION: Nearly 25% of patients with regrowth (unfavourable subgroup) experienced ultimate local failure, primarily due to refusing salvage TME. The risk of ultimate local failure in patients initiating radio(chemo)therapy as potential w&w candidates, or in patients starting w&w, appears comparable to that reported after preoperative chemoradiation and surgery. However, this comparison may be biased, because w&w studies included more early tumours compared with surgical studies.

Dosimetric comparison of three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and volumetric-modulated arc therapy for free-breathing whole-breast irradiation: A planning study.

Background: Currently, recommended heart dose constraints are difficult to meet in whole-breast irradiation (WBI) for left-sided breast cancer patients, who cannot be treated with the deep inspiration breath hold. We performed a radiotherapy planning study to establish if the use of intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) allows for better sparing of the heart and its subvolumes than the three-dimensional conformal radiation therapy (3D-CRT), and how these attempts affect the dose delivered to the other organs. Methods: A total of 17 left-sided and 10 right-sided consecutive patients treated with free-breathing WBI were retrospectively included. The 3D-CRT, IMRT, and VMAT plans were generated. Several dose-volume parameters and plan quality indices were compared, separately for the left- and right-sided plans. Results: All the techniques fulfilled the planning objectives. In the left-sided plans, there was no heart or left ventricle dose reduction with IMRT, nor with VMAT; the maximum dose in the left anterior descending coronary artery was reduced with VMAT (P = 0.005); V5 for the contralateral breast, contralateral lung, and total-body increased markedly in VMAT, and for the ipsilateral lung (V5IL) also in IMRT, compared with 3D-CRT (P < 0.001). In the right-sided plans, the V5 values, except for V5IL, did not differ between the three techniques. Conclusions: IMRT and VMAT had a limited heart-sparing benefit in the left-sided free-breathing WBI, at the cost of increased low-dose volumes, measured by V5. The low-dose volumes are not increased by IMRT or VMAT in the right-sided WBI, where heart sparing is not a problem, but the attempts to reduce cardiac doses in the left-sided WBI increase them.

The Role of Virtual Triage in Improving Clinician Experience and Satisfaction: A Narrative Review.

Objective: This review examines the literature on improving clinician satisfaction with a focus on what has been most effective in improving experience from the perspective of clinicians, and the potential role that virtual triage (VT) technology can play in delivering positive clinician experiences that improve clinical care, and bring value to health care delivery organizations (HDOs). Methods: Review and synthesis of evidence on clinician satisfaction indicating a potential for VT to favorably impact clinician experience, sense of effectiveness, efficiency, and reduction of administrative task burden. Analysis considers how to conceptualize and the value of improving clinician experience, leading clinician dissatisfiers, and the potential role of VT in improving clinician experience/satisfaction. Results: Contributors to poor clinician experience/satisfaction where VT could have a beneficial impact include better managing resource limitations, administrative workload, lack of care coordination, information overload, and payer interactions. VT can improve clinician experience through the technology's ability to leverage real-time actionable data clinicians can use, streamlining patient-clinician communications, personalizing care delivery, optimizing care coordination, and better aligning digital/virtual services with clinical practice. From an organizational perspective, improvements in clinician experience and satisfaction derive from establishing an effective digital back door, increasing the clinical impact of and satisfaction derived from telemedicine and virtual care, and enhancing clinician centricity. Conclusions: By embracing digital transformation and implementing solutions such as VT that focus on improving patient and clinician experience, HDOs can address barriers to delivery of high-quality, efficient, and cost-effective care. VT is a digital health tool that can create a more streamlined and satisfying experience for clinicians and the patients they care for. VT is a technology solution that can help clinicians make faster more informed decisions, reduces avoidable care, improves communication with patients and within care teams, and lowers their administrative burden so they have more quality time to care for patients.

Does the Gain of Total Neoadjuvant Therapy Outweigh the Harm in Rectal Cancer? Importance of the ATRESS (neoAdjuvant Therapy-RElated Shortening of Survival) Phenomenon: A Systematic Review.

BACKGROUND: We aimed to evaluate whether total neoadjuvant therapy (TNT) results in long-term overall survival (OS) or quality of life (QoL) benefit compared with chemoradiation if all patients are being considered for radical resection, and whether the ATRESS phenomenon (i.e., reduction in post-metastatic survival) impacts OS after TNT. METHODS: Systematic review of randomised trials comparing TNT with neoadjuvant (chemo)radiation. RESULTS: Six trials were identified. Follow-ups were too short to resolve whether TNT improves long-term OS. QoL analysis in one trial showed worse long-term neurotoxicity-related QoL (any neurotoxicity: 14% vs. 3%), higher rate of grade III+ acute toxicity (48% vs. 25%), longer duration of neoadjuvant treatment (19 vs. 6 weeks) and higher rate of locoregional failure (10% vs. 7%) in TNT vs. chemoradiation. This should be weighed against an absolute 8% reduction in the incidence of distant metastases (DM) after TNT. ATRESS could explain a discrepancy between reduction of DM and the absence of OS improvement after TNT in one trial. CONCLUSION: In the light of unproven OS benefit, the gain of TNT (reduction of DM) does not seem to outweigh the harm (excess of toxicity). ATRESS can be a reason for the absence of the OS benefit despite the reduction in DM.

The Evaluation of the Periodontal Status of Hemodialysis Patients with End-Stage Renal Disease.

Chronic kidney disease (CKD) is an increasingly common condition observed in developing countries. Similarly, a high prevalence of gingivitis and periodontitis is observed. There are reports in the literature about the interrelationship between chronic kidney disease and periodontitis pathophysiology. This dissertation attempts to: assess the extent of gingivitis and periodontitis in a group of patients with the end-stage renal disease treated with hemodialysis compared to healthy subjects. The study included 200 subjects: 100 hemodialysis patients (HD) and 100 healthy control subjects (K). Periodontal status was assessed by measuring pocket depth (PD) clinical level of connective tissue attachment (CAL). Gingival inflammation indices Gingival Index (GI) and Bleeding on Probing (BOP) were also performed. PD with a depth of more than 6mm was found in 25% of the HD group and 5% of the K group. CAL ≥ 5 mm was found in 55% of HD and 24% of the K group. As defined by Page and Eke, severe periodontitis was found in 21% of HD, and 4% of K. Moderate gingivitis was noted in 55% of HD and 5% of the K group. The mean values of the BOP index in the HD group were 32.08% and in the K group 3.09%. The HD group had a higher incidence and severity of gingivitis and periodontitis than the control group.

Contouring cardiac substructures on average intensity projection 4D-CT for lung cancer radiotherapy: A proposal of a heart valve contouring atlas.

BACKGROUND AND PURPOSE: A detailed contouring atlas of the heart valves is lacking. Existing heart contouring atlases have not been evaluated on average intensity projection four-dimensional non-contrast computed tomography (AVE-4D-CT) scans, routinely used for organ-at-risk delineation in lung cancer radiotherapy. We aimed to develop the heart valve contouring atlas and to assess inter-observer variation in delineation of the heart, its substructures, and coronary arteries on AVE-4D-CT scans, along with its impact on radiotherapy doses. MATERIALS AND METHODS: A heart valve contouring atlas was developed. Five radiation oncologists and four cardiologists delineated the valves according to this atlas, and the remaining heart substructures according to the existing atlases, on AVE-4D-CT scans of ten patients who underwent radio(chemo)therapy for NSCLC. The observer contours were then compared to the collectively defined "reference" contours. Spatial variation was assessed using the Sørensen-Dice similarity coefficient (DSC), directed average Hausdorff distance (DAH), directed Hausdorff distance (HD), and the mean distance to agreement (MDA). The effect of spatial variation on radiotherapy doses was assessed using the patients' treatment plans. RESULTS: Inter-observer contour overlap (mean DSC) was 0.68, 0.49, 0.45 and 0.45, and inter-observer contour separation (mean DAH) was 2.1, 3.4, 2.6 and 2.9 mm for the pulmonic (PV), aortic (AV), mitral (MV) and tricuspid valve (TV), respectively. Mean HD was higher for TV and MV (13.3 and 11.7 mm) than for AV and PV (7.8 and 7 mm). The highest mean MDA of 3.1 mm was found for AV, and the lowest (1.9 mm) for PV. Inter-observer agreement was the lowest for the coronary arteries, but statistically significant dose variation was found mainly in the left ventricular septal and anterior segments. CONCLUSION: Our atlas enables reproducible delineation of the heart valves. Delineation of the heart and its substructures on AVE-4D-CT scans is feasible, with inter-observer variability similar to that reported on conventional non-contrast CT scans.

Duration of acute esophageal toxicity in concomitant radio-chemotherapy for non-small cell lung cancer with different fractionation schedules.

OBJECTIVES: In our previous prospective trial on accelerated hypofractionated concomitant radiochemotherapy (AHRT-CHT) for non-small-cell lung cancer (NSCLC), the incidence of grade ≥3 acute esophageal toxicity (AET) was similar to that reported for conventionally fractionated concomitant radiochemotherapy (CFRT-CHT), but its duration was prolonged. Thus, we aimed to compare the duration of grade ≥3 AET between AHRT-CHT and CFRT-CHT. METHODS: Clinical data of 76 NSCLC patients treated with CFRT-CHT (60-66 Gy/2 Gy) during 2015-2020 were retrospectively compared with the data of 92 patients treated with AHRT-CHT (58.8 Gy/2.8 Gy) in the prospective trial. The maximum grade of AET, incidence, and duration of grade ≥3 AET were the end points. Univariate and multivariate analyses were applied to correlate clinical and treatment variables with these end points. RESULTS: Neither the maximum grade of AET (p = 0.71), nor the incidence of grade ≥3 AET (p = 0.87) differed between the two groups. The number of CHT cycles delivered (2 vs 1, p = 0.005) and higher esophagus mean BED (p = 0.009) were significant predictors for a higher maximum grade of AET; older age was a significant predictor for higher incidence of grade ≥3 AET (p = 0.03). The median duration of grade ≥3 AET in AHRT-CHT and CFRT-CHT group was 30 days (range 5-150) vs 7 days (range 3-20), respectively, p = 0.0005. In multivariate analysis, only the AHRT-CHT schedule (p=0.003) was a significant predictor for a longer duration of grade ≥3 AET. CONCLUSION: Despite similar incidence of grade ≥3 AET, its duration is significantly prolonged in NSCLC patients treated with AHRT-CHT compared to CFRT-CHT. ADVANCES IN KNOWLEDGE: Reporting only the rate of grade ≥3 AET in clinical trials may underestimate the real extent of the esophageal toxicity; its duration should also be routinely reported.

Radiotherapy for brain metastases from small-cell lung cancer in distinct clinical indications and scenarios.

Management of brain metastases (BM) from small-cell lung cancer (SCLC) is complex and not supported by a strong evidence from prospective clinical trials. Owing to the different clinical and pathological characteristics of SCLC, patients with this histology were not included in the prospective studies on the value of whole-brain radiotherapy (WBRT) and local surgical or ablative radiation treatment like stereotactic radiosurgery (SRS). Chemotherapy also represents a major part of the armamentarium against BM from SCLC due to the well-recognized chemoresponsiveness of this cancer and the frequent presentation of BM with extracranial progression. WBRT in combination with chemotherapy has long been a standard approach in this setting. However, data on the neurocognitive toxicity and the lack of documented impact on overall survival of WBRT in the management of BM from other solid tumors, as well as the increasing availability of the stereotactic radiotherapy technologies, has led to the increasing use of SRS with omission of WBRT also in SCLC. In the current review the use of different modalities of radiotherapy and ways of combining radiotherapy with chemotherapy for BM from SCLC will be presented for distinct clinical situations: presentation of BM synchronous with primary, metachronous presentation of BM-without previous prophylactic cranial irradiation (PCI) vs. after PCI, and asymptomatic BM found at the staging before PCI.

Management of brain metastases in elderly patients with lung cancer.

The incidence of brain metastases (BM) is continuing to grow in the elderly population with lung cancer, but these patients are seriously under-represented in clinical trials. Thus, their treatment is not based on the evidence from randomized prospective studies. Age is a well recognized poor prognostic factor for survival in patients with BM from lung cancer, which is reflected in prognostic scales, but its impact on the patients' prognosis reflected by its value in gradually updated grading indices seems to decrease. The reason for poorer outcomes in the elderly is unknown-it may result from the influence of the age per se, simplified staging work-up and suboptimal treatment in this patient subgroup or the excess toxicity of the aggressive anticancer treatment secondary to the impaired physiological regulation mechanisms and comorbidities. The main goal of treatment of BM is to ameliorate neurological symptoms and delay neurological progression, with the focus on the improvement and maintenance of the patients' quality of life. The possible treatment options for BM from lung cancer are whole-brain radiotherapy, stereotactic radiosurgery, surgery, chemotherapy, targeted therapies and best supportive care. The aim of this review is to summarize the problems related to the management of BM in elderly patients with lung cancer, to analyze the value of the above mentioned treatment options, and to provide an insight into the influence of age-related clinical factors on the patients' outcomes.