Acute hospitalizations after proton therapy versus intensity-modulated radiotherapy for locally advanced non-small cell lung cancer in the durvalumab era.

INTRODUCTION: It was hypothesized that use of proton beam therapy (PBT) in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiation and consolidative immune checkpoint inhibition is associated with fewer unplanned hospitalizations compared with intensity-modulated radiotherapy (IMRT). METHODS: Patients with locally advanced non-small cell lung cancer treated between October 2017 and December 2021 with concurrent chemoradiation with either IMRT or PBT ± consolidative immune checkpoint inhibition were retrospectively identified. Logistic regression was used to assess the association of radiation therapy technique with 90-day hospitalization and grade 3 (G3+) lymphopenia. Competing risk regression was used to compare G3+ pneumonitis, G3+ esophagitis, and G3+ cardiac events. Kaplan-Meier method was used for progression-free survival and overall survival. Inverse probability treatment weighting was applied to adjust for differences in PBT and IMRT groups. RESULTS: Of 316 patients, 117 (37%) received PBT and 199 (63%) received IMRT. The PBT group was older (p < .001) and had higher Charlson Comorbidity Index scores (p = .02). The PBT group received a lower mean heart dose (p < .0001), left anterior descending artery V15 Gy (p = .001), mean lung dose (p = .008), and effective dose to immune circulating cells (p < .001). On inverse probability treatment weighting analysis, PBT was associated with fewer unplanned hospitalizations (adjusted odds ratio, 0.55; 95% CI, 0.38-0.81; p = .002) and less G3+ lymphopenia (adjusted odds ratio, 0.55; 95% CI, 0.37-0.81; p = .003). There was no difference in other G3+ toxicities, progression-free survival, or overall survival. CONCLUSIONS: PBT is associated with fewer unplanned hospitalizations, lower effective dose to immune circulating cells and less G3+ lymphopenia compared with IMRT. Minimizing dose to lymphocytes may be warranted, but prospective data are needed.

Cardiac radiation dose is associated with inferior survival but not cardiac events in patients with locally advanced non-small cell lung cancer in the era of immune checkpoint inhibitor consolidation.

PURPOSE: We assessed the association of cardiac radiation dose with cardiac events and survival post-chemoradiation therapy (CRT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) after adoption of modern radiation therapy (RT) techniques, stricter cardiac dose constraints, and immune checkpoint inhibitor (ICI) consolidation. METHODS AND MATERIALS: This single-institution, multi-site retrospective study included 335 patients with LA-NSCLC treated with definitive, concurrent CRT between October 2017 and December 2021. All patients were evaluated for ICI consolidation. Planning dose constraints included heart mean dose < 20 Gy (<10 Gy if feasible) and heart volume receiving ≥ 50 Gy (V50Gy) < 25 %. Twenty-one dosimetric parameters for three different cardiac structures (heart, left anterior descending coronary artery [LAD], and left ventricle) were extracted. Primary endpoint was any major adverse cardiac event (MACE) post-CRT, defined as acute coronary syndrome, heart failure, coronary revascularization, or cardiac-related death. Secondary endpoints were: grade ≥ 3 cardiac events (per CTCAE v5.0), overall survival (OS), lung cancer-specific mortality (LCSM), and other-cause mortality (OCM). RESULTS: Median age was 68 years, 139 (41 %) had baseline coronary heart disease, and 225 (67 %) received ICI consolidation. Proton therapy was used in 117 (35 %) and intensity-modulated RT in 199 (59 %). Median LAD V15Gy was 1.4 % (IQR 0-22) and median heart mean dose was 8.7 Gy (IQR 4.6-14.4). Median follow-up was 3.3 years. Two-year cumulative incidence of MACE was 9.5 % for all patients and 14.3 % for those with baseline coronary heart disease. Two-year cumulative incidence of grade ≥ 3 cardiac events was 20.4 %. No cardiac dosimetric parameter was associated with an increased risk of MACE or grade ≥ 3 cardiac events. On multivariable analysis, cardiac dose (LAD V15Gy and heart mean dose) was associated with worse OS, driven by an association with LCSM but not OCM. CONCLUSIONS: With modern RT techniques, stricter cardiac dose constraints, and ICI consolidation, cardiac dose was associated with LCSM but not OCM or cardiac events in patients with LA-NSCLC.

Pneumonitis Rates Before and After Adoption of Immunotherapy Consolidation in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Concurrent Chemoradiation.

PURPOSE: We hypothesized that after adoption of immune checkpoint inhibitor (ICI) consolidation for patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving concurrent chemoradiation therapy (cCRT), rates of symptomatic pneumonitis would increase, thereby supporting efforts to reduce lung radiation dose. METHODS AND MATERIALS: This single institution, multisite retrospective study included 783 patients with LA-NSCLC treated with definitive cCRT either before introduction of ICI consolidation (pre-ICI era cohort [January 2011-September 2017]; N = 448) or afterward (ICI era cohort [October 2017-December 2021]; N = 335). Primary endpoint was grade ≥2 pneumonitis (G2P) and secondary endpoint was grade ≥3 pneumonitis (G3P), per Common Terminology Criteria for Adverse Events v5.0. Pneumonitis was compared between pre-ICI era and ICI era cohorts using the cumulative incidence function and Gray's test. Inverse probability of treatment weighting (IPTW)-adjusted Fine-Gray models were generated. Logistic models were developed to predict the 1-year probability of G2P as a function of lung dosimetry. RESULTS: G2P was higher in the ICI era than in the pre-ICI era (1-year cumulative incidence 31.4% vs 20.1%; P < .001; IPTW-adjusted multivariable subdistribution hazard ratio, 2.03; 95% confidence interval, 1.53-2.70; P < .001). There was no significant interaction between ICI era treatment and either lung volume receiving ≥20 Gy (V20) or mean lung dose in Fine-Gray regression for G2P; however, the predicted probability of G2P was higher in the ICI era at clinically relevant values of lung V20 (≥24%) and mean lung dose (≥14 Gy). Cut-point analysis revealed a lung V20 threshold of 28% in the ICI era (1-year G2P rate 46.0% above vs 19.8% below; P < .001). Among patients receiving ICI consolidation, lung V5 was not associated with G2P. G3P was not higher in the ICI era (1-year cumulative incidence 7.5% vs 6.0%; P = .39; IPTW-adjusted multivariable subdistribution hazard ratio, 1.12; 95% confidence interval, 0.63-2.01; P = .70). CONCLUSIONS: In patients with LA-NSCLC treated with cCRT, the adoption of ICI consolidation was associated with an increase in G2P but not G3P. With ICI consolidation, stricter lung dose constraints may be warranted.

Phase 2 Trial of Consolidation Pembrolizumab After Proton Reirradiation for Thoracic Recurrences of Non-Small Cell Lung Cancer.

PURPOSE: Reirradiation (reRT) with proton beam therapy (PBT) may offer a chance of cure while minimizing toxicity for patients with isolated intrathoracic recurrences of non-small cell lung cancer (NSCLC). However, distant failure remains common, necessitating strategies to integrate more effective systemic therapy. METHODS AND MATERIALS: This was a phase 2, single-arm trial (NCT03087760) of consolidation pembrolizumab after PBT reRT for locoregional recurrences of NSCLC. Four to 12 weeks after completion of 60 to 70 Gy PBT reRT, patients without progressive disease received pembrolizumab for up to 12 months. Primary endpoint was progression-free survival (PFS), measured from the start of reRT. Secondary endpoints were overall survival (OS) and National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 toxicity. RESULTS: Between 2017 and 2021, 22 patients received PBT reRT. Median interval from prior radiation end to reRT start was 20 months. Most recurrences (91%) were centrally located. Most patients received concurrent chemotherapy (95%) and pencil beam scanning PBT (77%), and 36% had received prior durvalumab. Fifteen patients (68%) initiated consolidation pembrolizumab on trial and received a median of 3 cycles (range, 2-17). Pembrolizumab was discontinued most commonly due to toxicity (n = 5; 2 were pembrolizumab-related), disease progression (n = 4), and completion of 1 year (n = 3). Median follow-up was 38.7 months. Median PFS and OS were 8.8 months (95% CI, 4.2-23.7) and 22.8 months (95% CI, 6.9-not reached), respectively. There was only one isolated in-field failure after reRT. Grade ≥3 toxicities occurred in 10 patients (45%); 2 were pembrolizumab-related. There were 2 grade 5 toxicities, an aorto-esophageal fistula at 6.9 months and hemoptysis at 46.8 months, both probably from reRT. The trial closed early due to widespread adoption of immunotherapy off-protocol. CONCLUSIONS: In the first-ever prospective trial combining PBT reRT with consolidation immunotherapy, PFS was acceptable and OS favorable. Late grade 5 toxicity occurred in 2 of 22 patients. This approach may be considered in selected patients with isolated thoracic recurrences of NSCLC.

Patterns of Failure, Low-Volume Relapse, and Subsequent Ablative Management in Locally Advanced Non-Small Cell Lung Cancer Treated With Definitive Chemoradiation and Consolidation Immune Checkpoint Inhibitors.

PURPOSE: The objective of this study was to describe the patterns of failure, frequency of low-volume relapse (LVR), and candidacy for ablative therapy at time of disease progression (PD) after chemoradiation and consolidative immunotherapy (CRT + ICI) in patients with stage III non-small cell lung cancer. METHODS AND MATERIALS: We identified 229 consecutive patients with stage III non-small cell lung cancer treated with CRT + ICI between October 2017 and December 2021 at a single institution. PD was classified as isolated locoregional failure (LRF), isolated distant failure (DF), or synchronous LRF + DF. Any LRF was subclassified as in-field failure, marginal failure, or out-of-field failure. LVR was defined as 3 or fewer sites of PD in any number of organs. Ablative candidates were defined as having 5 or fewer sites of PD radiographically amenable to high-dose radiation or surgery. Time-to-event data were calculated using cumulative incidence analysis and Kaplan-Meier methods. Multivariable Cox modeling was used to examine the correlations between characteristics of relapse and postprogression survival. RESULTS: Of the 229 patients, 119 (52%) had PD. Of these 119 patients, 20 (21%) had isolated LRF, 28 (24%) had synchronous LRF + DF, and 71 (60%) had isolated DF. Of the 48 patients with any LRF, 28 (58%) had in-field failure, 10 (21%) marginal failure, and 10 (21%) out-of-field failure. The cumulative incidence of LRF and DF was 13% (95% CI, 9.2%-18%) and 32% (95% CI, 26%-38%) at 1 year and 19% (95% CI, 14%-24%) and 39% (95% CI, 33%-46%) at 2 years, respectively. Overall, 64 patients (54%) were considered to have LVR. At time of PD, 60 patients (50%) were eligible for ablative therapy. Patients with LVR had longer median survival versus with high-volume relapse (37.4 vs 15.2 months, P < .001). On multivariable analysis, LVR (hazard ratio, 0.32; 95% CI, 0.18-0.56; P < .001) was associated with improved postprogression survival. CONCLUSIONS: After CRT + ICI, approximately half of patients experience LVR at time of PD and are candidates for ablative therapies. Prospective trials are needed to validate the optimal treatment strategy for LVR.

The effective radiation dose to immune cells predicts lymphopenia and inferior cancer control in locally advanced NSCLC.

PURPOSE: To explore the association of the effective dose to immune cells (EDIC) with disease control, lymphopenia, and toxicity in patients with non-small cell lung cancer (NSCLC) and identify methods to reduce EDIC. METHODS: We abstracted data from all patients with locally advanced NSCLC treated with chemoradiation with or without consolidative immunotherapy over a ten-year period. Associations between EDIC and progression-free survival (PFS) and overall survival (OS) were modeled with Cox proportional hazards and Kaplan-Meier method. Logistic regression was used to model predictors of lymphopenia and higher EDIC. Analyses were performed with EDIC as a continuous and categorical variable. Lymphopenia was graded per CTCAE v5.0. RESULTS: Overall, 786 patients were included (228 of which received consolidative immunotherapy); median EDIC was 4.7 Gy. Patients with EDIC < 4.7 Gy had a longer median PFS (15.3 vs. 9.0 months; p < 0.001) and OS (34.2 vs. 22.4 months; p < 0.001). On multivariable modeling, EDIC correlated with inferior PFS (HR 1.08, 95 % CI 1.01-1.14, p = 0.014) and OS (HR 1.10, 95 % CI 1.04-1.18, p = 0.002). EDIC was predictive of grade 4 lymphopenia (OR 1.16, 95 % CI 1.02-1.33, p = 0.026). EDIC ≥ 4.7 Gy was associated with increased grade 2 + pneumonitis (6-month incidence: 26 % vs 20 %, p = 0.04) and unplanned hospitalizations (90-day incidence: 40 % vs 30 %, p = 0.002). Compared to protons, photon therapy was associated with EDIC ≥ 4.7 Gy (OR 5.26, 95 % CI 3.71-7.69, p < 0.001) in multivariable modeling. CONCLUSIONS: EDIC is associated with inferior disease outcomes, treatment-related toxicity, and the development of severe lymphopenia. Proton therapy is associated with lower EDIC. Further investigations to limit radiation dose to the immune system appear warranted.

Patterns of Failure in Metastatic NSCLC Treated With First Line Pembrolizumab and Use of Local Therapy in Patients With Oligoprogression.

INTRODUCTION: The patterns of failure (POF) for metastatic non-small-cell lung cancer (mNSCLC) treated with immunotherapy are not well established. METHODS: We conducted a retrospective cohort study of mNSCLC that received first-line pembrolizumab with or without chemotherapy at a single academic center from 2015 to 2021. We defined POF with 2 classifications: 1) local, regional, or distant failure, or 2) failure in existing lesions, new lesions, or a combination. Oligoprogression was defined as disease progression (PD) in ≤3 sites of failure. Overall survival (OS) was measured via Kaplan-Meier and modelled with Cox regression. RESULTS: Of 298 patients identified, 198 had PD. Using POF classification 1, most failures were distant (43.9%) or a combination of locoregional and distant (34.4%). For POF classification 2, failures occurred in a combination of new and existing lesions (45.0%), existing lesions alone (33.3%), or in new lesions only (21.7%). Oligoprogression occurred in 39.9% (n = 79) cases. Median OS was higher in the following: PD in existing lesions vs. new or new + existing lesions (28.7 vs. 20.2 vs. 13.9 months, P < .001) and oligoprogression vs. polyprogression (35.1 vs. 12.2 months, P < .001). In oligoprogression, median OS was better for those who received radiation to all sites of PD (62.2 months) than for those who changed systemic therapy (22.9 months, P = .007). On multivariable analysis, radiation for oligoprogression (HR 0.35, 95% CI: 0.20-0.62, P < .001) was associated with improved OS. CONCLUSIONS: In mNSCLC treated with pembrolizumab, oligoprogression is relatively common. Randomized data are needed to define the benefits of radiation in oligoprogressive mNSCLC.

Utilization and Factors Precluding Receipt of Checkpoint Inhibitor Consolidation for Stage III NSCLC in a Large US Academic Health System.

OBJECTIVES: We sought to determine the proportion of patients with stage III non-small cell lung cancer (NSCLC) who initiate consolidation durvalumab or other immune checkpoint inhibitors (ICIs) after concurrent chemoradiotherapy (cCRT), as well as reasons for nonreceipt and prognostic implications. MATERIALS AND METHODS: We retrospectively identified consecutive patients with unresectable stage III NSCLC treated with definitive cCRT between October 2017 and December 2021 within a large US academic health system. Patients either received consolidation ICIs (ICI group) or did not (no-ICI group). Baseline characteristics and overall survival (OS) of the groups were assessed. Factors predictive of ICI nonreceipt were evaluated using logistic regression. RESULTS: Of 333 patients who completed cCRT, 229 (69%) initiated consolidation ICIs; 104 (31%) did not. Reasons for ICI nonreceipt included progressive disease post-cCRT (N = 31, 9%), comorbidity or intercurrent illness (N = 25, 8%), cCRT toxicity (N = 23, 7%; 19/23 pneumonitis), and EGFR/ALK alteration (N = 14, 4%). The no-ICI group had worse performance status and a higher rate of baseline pulmonary comorbidity. Larger planning target volume was associated with post-cCRT progressive disease, and higher lung radiation dose with cCRT toxicity. Median OS was 16 months in the no-ICI group and 34.4 months in the ICI group. In the no-ICI group, OS was superior among those with EGFR/ALK alterations (median 44.5 months) and worst among those with progressive disease (median 5.9 months, P < 0.001). CONCLUSION: 31% of patients who completed cCRT for stage III NSCLC did not receive consolidation ICIs. Survival amongst these patients is poor, especially for those with progressive disease post-cCRT.

Palliative Care Delivery Systems and Integration With Palliative Care Teams.

Radiotherapy (RT) plays a critical role in the palliation of symptoms in patients with advanced or metastatic cancer. To address the growing need for these services, multiple dedicated palliative RT programs have been established. This article serves to highlight the novel ways in which palliative RT delivery systems support patients with advanced cancer. Through early integration of multidisciplinary palliative supportive services, rapid access programs facilitate best practices for oncologic patients at the end of life.

Association of cardiac calcium burden with overall survival after radiotherapy for non-small cell lung cancer.

Background and purpose: Coronary calcifications are associated with coronary artery disease in patients undergoing radiotherapy (RT) for non-small cell lung cancer (NSCLC). We quantified calcifications in the coronary arteries and aorta and investigated their relationship with overall survival (OS) in patients treated with definitive RT (Def-RT) or post-operative RT (PORT). Materials and methods: We analyzed 263 NSCLC patients treated from 2004 to 2017. Calcium burden was ascertained with a Hounsfield unit (HU) cutoff of > 130 in addition to a deep learning (DL) plaque estimator. The HU cutoff volumes were defined for coronary arteries (PlaqueCoro) and coronary arteries and aorta combined (PlaqueCoro+Ao), while the DL estimator ranged from 0 (no plaque) to 3 (high plaque). Patient and treatment characteristics were explored for association with OS. Results: The median PlaqueCoro and PlaqueCoro+Ao was 0.75 cm3 and 0.87 cm3 in the Def-RT group and 0.03 cm3 and 0.52 cm3 in the PORT group. The median DL estimator was 2 in both cohorts. In Def-RT, large PlaqueCoro (HR:1.11 (95%CI:1.04-1.19); p = 0.008), and PlaqueCoro+Ao (HR:1.06 (95%CI:1.02-1.11); p = 0.03), and poor Karnofsky Performance Status (HR: 0.97 (95%CI: 0.94-0.99); p = 0.03) were associated with worse OS. No relationship was identified between the plaque volumes and OS in PORT, or between the DL plaque estimator and OS in either Def-RT or PORT. Conclusions: Coronary artery calcification assessed from RT planning CT scans was significantly associated with OS in patients who underwent Def-RT for NSCLC. This HU thresholding method can be straightforwardly implemented such that the role of calcifications can be further explored.

Plunging Into the PACIFIC: Outcomes of Patients With Unresectable KRAS-Mutated Non-Small Cell Lung Cancer Following Definitive Chemoradiation and Durvalumab Consolidation.

BACKGROUND: Immune checkpoint inhibitor (ICI) consolidation following concurrent chemoradiotherapy (CRT) substantially improved progression free survival (PFS) and overall survival (OS) in the PACIFIC trial becoming the standard of care in locally-advanced, unresectable NSCLC. KRAS mutation may influence response to ICI. METHODS: In this single-institution, retrospective analysis, we compared treatment outcomes for patients with unresectable KRAS mutated (KRAS-mt) and wild-type (KRAS-wt) NSCLC treated with CRT between October 2017 and December 2021. Kaplan-Meier analysis was conducted comparing median progression free survival and median overall survival from completion of radiotherapy in all KRAS-mt patients and KRAS-G12C-mutated patients. Outcomes were also compared with and without ICI consolidation. RESULTS: Of 156 patients, 42 (26.9%) were KRAS-mt and 114 (73.1%) were KRAS-wt. Baseline characteristics differed only in histology; KRAS-mt NSCLC more likely to be adenocarcinoma. KRAS-mt patients had worse PFS (median 6.3 vs. 10.7 months, P = .041) but similar OS (median 23.1 vs. 27.3 months, P = .237). KRAS-mt patients were more likely to not receive ICI due to rapid disease progression post-CRT (23.8% vs. 4.4%, P = .007). Among patients who received ICI (n = 114), KRAS-mt was not associated with inferior PFS (8.1 vs. 11.9 months, P = .355) or OS (30.5 vs. 31.7 months, P = .692). KRAS-G12C patients (n = 22) had similar PFS and OS to other KRAS-mt. CONCLUSION: In one of the largest post-CRT KRAS-mt cohort published, KRAS-mt was associated with inferior PFS, largely due to rapid progression prior to ICI consolidation, but did not affect OS. Among those who received ICI consolidation, outcomes were comparable regardless of KRAS-mt status.

Increasing Heart Dose Reduces Overall Survival in Patients Undergoing Postoperative Radiation Therapy for NSCLC.

INTRODUCTION: Given the concern for cardiopulmonary toxicity in patients with NSCLC undergoing postoperative radiation therapy (PORT), the purpose of this study was to evaluate the association between heart dose and overall survival (OS) in patients undergoing PORT with modern techniques. METHODS: This is a retrospective study of consecutive patients with NSCLC treated with PORT between May 2004 and January 2017. Clinical records were reviewed and radiation dose distributions were analyzed for association with OS. RESULTS: A total of 284 patients were analyzed. At the time of surgery, most patients had pathologic American Joint Committee on Cancer seventh edition stage III disease (91.2 %) and received either preoperative or adjuvant chemotherapy (92.3 %). Most patients underwent a lobectomy (81.3 %) and had R0 (80.6 %) or R1 (19.4 %) resection. PORT was delivered with a median radiation dose of 54 Gy, and 70.4 % of patients were treated with intensity-modulated radiation therapy. Dosimetric variables across a large range of doses to the heart were highly significant (p < 0.05) for OS. The volume of the heart receiving 8 Gy (HV8) was the most significant dosimetric variable (p < 0.001), and the median HV8 was 35.5 %. The median OS was 33.2 versus 53.6 months (p < 0.005) for patients with HV8 above or below 35.5 %, respectively. On multivariable analysis accounting for other potential prognostic confounders, HV8 remained highly significant (p < 0.001). CONCLUSIONS: The data reveal a strong correlation between increasing heart dose and OS in patients with NSCLC undergoing PORT. Taken together with the recently presented LungART trial, lowering heart dose in PORT patients may help to decrease the risk of morbidity and mortality and improve the therapeutic ratio of PORT.

Clinical and Dosimetric Predictors of Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Undergoing Postoperative Radiation Therapy.

PURPOSE: Radiation pneumonitis (RP) is a common and potentially life-threatening toxicity from lung cancer radiation therapy. Data sets reporting RP rates after postoperative radiation therapy (PORT) have historically been small and with predominantly outdated field designs and radiation techniques. We examined a large cohort of patients in this context to assess the incidence and causes of RP in the modern era. METHODS AND MATERIALS: We reviewed 285 patients with non-small cell lung cancer treated with PORT at our institution from May 2004 to January 2017. Complete dosimetric data and clinical records were reviewed and analyzed with grade 2 or higher RP as the endpoint (RP2+) (Common Terminology Criteria for Adverse Events v4.0). Patients were a median of 67 years old (range, 28-87), and most had pathologic stage III non-small cell lung cancer (91%) and received trimodality therapy (90%). Systematic dosimetric analyses using Dx increments of 5% and Vx increments of 2 Gy were performed to robustly evaluate dosimetric variables. Lung V5 was also evaluated. RESULTS: The incidence of RP2+ after PORT was 12.6%. Dosimetric factors most associated with RP2+ were total lungV4 (hazard ratio [HR] 1.04, P < .001) and heart V16 (HR 1.03, P = .001). On univariate analysis, the clinical factors of age (HR 1.05, P = .006) and carboplatin chemotherapy (HR 2.32, P = .012) were correlated with RP2+. On step-up multivariate analysis, only bivariate models remained significant, including lungV5 (HR 1.037, P < .001) and age (HR 1.052, P = .011). CONCLUSIONS: The incidence of RP after PORT is consistent with the literature. Factors correlated with RP include lung and heart doses, age, and carboplatin chemotherapy. These data also suggest that elderly patients may be more susceptible to lower doses of radiation to the lung. Based on these data, dose constraints to limit the risk of RP2+ to <5% in the setting of PORT include lungV5 ≤65% in patients <65 years old and lungV5 ≤36% in patients 65 years or older.

Prostate Fiducial Marker Placement in Patients on Anticoagulation: Feasibility Prior to Prostate SBRT.

Background and Purpose: Fiducial marker placement is required in patients undergoing robotic-based Stereotactic Body Radiotherapy (SBRT) or image-guided radiation therapy (IGRT) for prostate cancer. Many patients take antiplatelet or anticoagulant medication due to other medical comorbidities. They are often required to temporarily discontinue these medications prior to invasive medical procedures as they are prone to bleed. Some patients are unable to discontinue therapy due to an elevated risk of thromboembolic events. The purpose of this study is to report this institution's experience placing fiducial markers in prostate cancer patients who are on chronic antiplatelet or anticoagulant medication. Materials and Methods: From August 2015-March 2019 57 patients on chronic antiplatelet or anticoagulation therapy who were not cleared to stop these medications underwent transrectal ultrasound guided (TRUS) fiducial marker placement for SBRT/IGRT. All patients were monitored by a registered nurse during the procedure for prolonged bleeding that required staff to hold pressure to the area with a 4 × 4 gauze until it resolved. All patients were also called the following day to assess for ongoing bleeding events. Treatment planning CT scan confirmed the ideal geometry of the marker placement. Results: All 57 patients on antiplatelet or anticoagulant medication who underwent fiducial marker placement were discharged home the same day of the procedure. Four patients experienced persistent bleeding that required a nurse to hold prolonged pressure to the area. No patient experienced significant bleeding the following day or any untoward cardiovascular event. Conclusions: This series suggests the use of antiplatelet or anticoagulant medication is not an absolute contraindication to fiducial marker placement in patients undergoing SBRT or IGRT for prostate cancer. These patients should be closely monitored after the procedure for bleeding complications. Practitioners may consider the patient's medical comorbidities, risk factors for thromboembolism, and overall functional status as there is no standardized protocol for discontinuing anticoagulant or antiplatelet therapy for fiducial marker placement.

Hypofractionated vs. conventional radiation therapy for stage III non-small cell lung cancer treated without chemotherapy.

Background: Patients with unresectable locally advanced NSCLC who refuse or are not candidates for chemotherapy often receive radiation therapy (RT) alone. Hypofractionated RT (HFRT) regimens are becoming increasingly common. An analysis of the National Cancer Database (NCDB) was performed to evaluate the practice patterns and outcomes of HFRT vs. conventionally fractionated RT (CFRT) in patients with stage III NSCLC undergoing definitive RT alone.Material and methods: The NCDB was queried for all patients with stage III NSCLC diagnosed between 2004 and 2014 who received RT alone. CFRT was defined as patients treated to a total dose of 60-80 Gy in 1.8-2 Gy daily fractions. HFRT was defined as patients treated to a total dose of 50-80 Gy in 2.25-4 Gy fractions. Logistic regression, univariable and multivariable analyses (MVAs) for overall survival (OS) and propensity score matched analyses (PSMAs) were performed.Results: A total of 6490 patients were evaluated: 5378 received CFRT and 1112 received HFRT. Median CFRT dose was 66 Gy in 2 Gy fractions vs. 58.5 Gy in 2.5 Gy fractions for HFRT. HFRT was associated with older age, lower biological effective dose (BED10), academic facility type, higher T-stage and lower N-stage. On initial analysis, HFRT was associated with inferior OS (median 9.9 vs. 11.1 months, p<.001), but after adjusting for the imbalance in covariates such as age, BED10, T-stage and N-stage using PSMA, the difference in survival was no longer significant (p=.1).Conclusions: In the appropriate clinical context, HFRT can be an option for patients with locally advanced NSCLC who are not candidates for chemotherapy or surgical resection. HFRT needs to be further studied in prospective trials to evaluate toxicity and tumor control.

The QuitIT Coping Skills Game for Promoting Tobacco Cessation Among Smokers Diagnosed With Cancer: Pilot Randomized Controlled Trial.

BACKGROUND: Although smoking cessation apps have become popular, few have been tested in randomized clinical trials or undergone formative evaluation with target users. OBJECTIVE: We developed a cessation app targeting tobacco-dependent cancer patients. Game design and behavioral rehearsal principles were incorporated to help smokers identify, model, and practice coping strategies to avoid relapse to smoking. In this randomized pilot trial, we examined feasibility (recruitment and retention rates), acceptability (patient satisfaction), quitting self-confidence, and other cessation-related indices to guide the development of a larger trial. METHODS: We randomized 42 English-speaking cancer patients scheduled for surgical treatment to either the Standard Care (SC; telecounseling and cessation pharmacotherapies) or the experimental QuitIT study arm (SC and QuitIT game). Gameplay parameters were captured in-game; satisfaction with the game was assessed at 1-month follow-up. We report study screening, exclusion, and refusal reasons; compare refusal and attrition by key demographic and clinical variables; and report tobacco-related outcomes. RESULTS: Follow-up data were collected from 65% (13/20) patients in the QuitIT and 61% (11/18) in SC arms. Study enrollees were 71% (27/38) females, 92% (35/38) white people, and 95% (36/38) non-Hispanic people. Most had either lung (12/38, 32%) or gastrointestinal (9/38, 24%) cancer. Those dropping out were less likely than completers to have used a tablet (P<.01) and have played the game at all (P=.02) and more likely to be older (P=.05). Of 20 patients in the QuitIT arm, 40% (8/20) played the game (system data). There were no differences between those who played and did not play by demographic, clinical, technology use, and tobacco-related variables. Users completed an average of 2.5 (SD 4.0) episodes out of 10. A nonsignificant trend was found for increased confidence to quit in the QuitIT arm (d=0.25, 95% CI -0.56 to 1.06), and more participants were abstinent in the QuitIT group than in the SC arm (4/13, 30%, vs 2/11, 18%). Satisfaction with gameplay was largely positive, with most respondents enjoying use, relating to the characters, and endorsing that gameplay helped them cope with actual smoking urges. CONCLUSIONS: Recruitment and retention difficulties suggest that the perihospitalization period may be a less than ideal time for delivering a smoking cessation app intervention. Framing of the app as a "game" may have decreased receptivity as participants may have been preoccupied with hospitalization demands and illness concerns. Less tablet experience and older age were associated with participant dropout. Although satisfaction with the gameplay was high, 60% (12/20) of QuitIT participants did not play the game. Paying more attention to patient engagement, changing the intervention delivery period, providing additional reward and support for use, and improving cessation app training may bolster feasibility for a larger trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT01915836; https://clinicaltrials.gov/ct2/show/NCT01915836 (Archived by WebCite at http://www.webcitation.org/73vGsjG0Y).

An eHealth Intervention to Increase Physical Activity and Healthy Eating in Older Adult Cancer Survivors: Summative Evaluation Results.

BACKGROUND: A healthy lifestyle is associated with improved quality of life among cancer survivors, yet adherence to health behavior recommendations is low. OBJECTIVE: This pilot trial developed and tested the feasibility of a tailored eHealth program to increase fruit and vegetable consumption and physical activity among older, long-term cancer survivors. METHODS: American Cancer Society (ACS) guidelines for cancer survivors were translated into an interactive, tailored health behavior program on the basis of Social Cognitive Theory. Patients (N=86) with a history of breast (n=83) or prostate cancer (n=3) and less than 5 years from active treatment were randomized 1:1 to receive either provider advice, brief counseling, and the eHealth program (intervention) or advice and counseling alone (control). Primary outcomes were self-reported fruit and vegetable intake and physical activity. RESULTS: About half (52.7%, 86/163) of the eligible patients consented to participate. The most common refusal reasons were lack of perceived time for the study (32/163) and lack of interest in changing health behaviors (29/163). Furthermore, 72% (23/32) of the intervention group reported using the program and most would recommend it to others (56%, 14/25). Qualitative results indicated that the intervention was highly acceptable for survivors. For behavioral outcomes, the intervention group reported increased fruit and vegetable consumption. Self-reported physical activity declined in both groups. CONCLUSIONS: The brief intervention showed promising results for increasing fruit and vegetable intake. Results and participant feedback suggest that providing the intervention in a mobile format with greater frequency of contact and more indepth information would strengthen treatment effects.