Associations Between Spirituality, Mindfulness, and Psychological Symptoms Among Advanced Lung Cancer Patients and Their Spousal Caregivers.

CONTEXT: Patients with metastatic lung cancer and their spousal caregivers are at high risk of psychological symptoms. Mindfulness may improve psychological symptoms via spiritual well-being (SW); yet, this mediation model has not been examined in a dyadic context. OBJECTIVES: We examined the mediating role of two dimensions of SW (meaning/peace and faith) in the mindfulness-symptoms link in Stage IV lung cancer patients and their spousal caregivers. METHODS: We examined the actor-partner interdependence model of mediation using multivariate multilevel modeling with 78 couples. Four actor-partner interdependence model of mediation analyses were conducted to examine one predictor (mindfulness) × two mediators (meaning/peace and faith) × two psychological symptoms (depressive symptoms and cancer distress). We also tested four alternative models in which mindfulness mediates the associations between SW and psychological symptoms. RESULTS: The alternative model (SW → mindfulness → psychological symptoms) was preferred than the original model (mindfulness → SW → psychological symptoms). For patients, meaning/peace was directly associated with their own psychological symptoms, whereas faith was only indirectly associated with their own psychological symptoms via mindfulness. For spouses, meaning/peace was both directly and indirectly associated with their own psychological symptoms, whereas faith was only directly associated with their own depressive symptoms (but not cancer distress). Moreover, spouses' faith was indirectly associated with patients' psychological symptoms through patients' mindfulness. CONCLUSION: SW is associated with patients' and spouses' psychological symptoms both directly and indirectly through mindfulness. Thus, interventions that target SW, particularly meaning and peace, along with mindfulness may be beneficial to the psychological management of patients facing a terminal disease and their spousal caregivers.

A Mindfulness-Based Intervention as a Supportive Care Strategy for Patients with Metastatic Non-Small Cell Lung Cancer and Their Spouses: Results of a Three-Arm Pilot Randomized Controlled Trial.

BACKGROUND: Although mindfulness-based interventions have been widely examined in patients with nonmetastatic cancer, the feasibility and efficacy of these types of programs are largely unknown for those with advanced disease. We pilot-tested a couple-based meditation (CBM) relative to a supportive-expressive (SE) and a usual care (UC) arm targeting psychospiritual distress in patients with metastatic lung cancer and their spousal caregivers. PATIENTS AND METHODS: Seventy-five patient-caregiver dyads completed baseline self-report measures and were then randomized to one of the three arms. Couples in the CBM and SE groups attended four 60-minute sessions that were delivered via videoconference. All dyads were reassessed 1 and 3 months later. RESULTS: A priori feasibility benchmarks were met. Although attendance was high in both groups, dyads in the CBM group indicated greater benefit of the sessions than those in the SE group (patients, CBM mean = 2.63, SE mean = 2.20, p = .003; spouses, CBM mean = 2.71, SE mean = 2.00, p = .005). Compared with the UC group, patients in the CBM group reported significantly lower depressive symptoms (p = .05; d = 0.53) and marginally reduced cancer-related stress (p = .07; d = 0.68). Medium effect sizes in favor of the CBM compared with the SE group for depressive symptoms (d = 0.59) and cancer-related stress (d = 0.54) were found. Spouses in the CBM group reported significantly lower depressive symptoms (p < .01; d = 0.74) compared with those in the UC group. CONCLUSION: It seems feasible and possibly efficacious to deliver dyadic interventions via videoconference to couples coping with metastatic lung cancer. Mindfulness-based interventions may be of value to managing psychological symptoms in the palliative care setting. Clinical trial identification number. NCT02596490 IMPLICATIONS FOR PRACTICE: The current randomized controlled trial has established that a mindfulness approach to the management of patients' and spouses' psychospiritual concerns is acceptable and subjectively deemed more beneficial than a supportive-expressive treatment for patients with metastatic non-small cell lung cancer (NSCLC). We also revealed that videoconference delivery, here FaceTime, is an acceptable approach even for geriatric patients with metastatic NSCLC and that patients and their spousal caregivers prefer a dyadic delivery of this type of supportive care strategy. Lastly, this trial has laid the foundation for the role of mindfulness-based interventions in the palliative care setting supporting patients with advanced NSCLC and their spousal caregivers.

Dyadic yoga program for patients undergoing thoracic radiotherapy and their family caregivers: Results of a pilot randomized controlled trial.

OBJECTIVE: Thoracic radiotherapy (TRT) may result in toxicities that are associated with performance declines and poor quality of life (QOL) for patients and their family caregivers. The purpose of this randomized controlled trial was to establish feasibility and preliminary efficacy of a dyadic yoga (DY) intervention as a supportive care strategy. METHODS: Patients with stage I to III non-small cell lung or esophageal cancer undergoing TRT and their caregivers (N = 26 dyads) were randomized to a 15-session DY or a waitlist control (WLC) group. Prior to TRT and randomization, both groups completed measures of QOL (SF-36) and depressive symptoms (CES-D). Patients also completed the 6-minute walk test (6MWT). Dyads were reassessed on the last day of TRT and 3 months later. RESULTS: A priori feasibility criteria were met regarding consent (68%), adherence (80%), and retention (81%) rates. Controlling for relevant covariates, multilevel modeling analyses revealed significant clinical improvements for patients in the DY group compared with the WLC group for the 6MWT (means: DY = 473 m vs WLC = 397 m, d = 1.19) and SF-36 physical function (means: DY = 38.77 vs WLC = 30.88; d = .66) and social function (means: DY = 45.24 vs WLC = 39.09; d = .44) across the follow-up period. Caregivers in the DY group reported marginally clinically significant improvements in SF-36 vitality (means: DY = 53.05 vs WLC = 48.84; d = .39) and role performance (means: DY = 52.78 vs WLC = 48.59; d = .51) relative to those in the WLC group. CONCLUSIONS: This novel supportive care program appears to be feasible and beneficial for patients undergoing TRT and their caregivers. A larger efficacy trial with a more stringent control group is warranted.

Pilot Testing of a Brief Couple-Based Mind-Body Intervention for Patients With Metastatic Non-Small Cell Lung Cancer and Their Partners.

CONTEXT: Given the generally incurable nature of metastatic lung cancer, patients and their spouses/partners are at risk for psychological and spiritual distress. To address this concern, we developed a couple-based mind-body (CBMB) intervention. OBJECTIVES: This formative research aimed at examining the intervention's acceptability and initial efficacy in patients with metastatic lung cancer undergoing treatment and their spouses. METHODS: Intervention content evaluation sessions and an ensuing single-arm trial were conducted. To evaluate intervention content, participants performed intervention exercises and then participated in semistructured interviews and completed written evaluations. In the single-arm trial, four intervention sessions were delivered over two weeks, focusing on cultivating mindfulness, interpersonal connection, gratitude, and purpose. Newly recruited couples completed measures of depressive symptoms, cancer distress, spiritual well-being, and sleep disturbances before and after the intervention. RESULTS: Content evaluations by seven dyads of patients and their partners revealed high acceptability ratings for the CBMB intervention (e.g., all participants would recommend the intervention). Consent and adherence rates (54% and 67%, respectively) were acceptable in the single-arm trial. All patients (n = 7 dyads; 67% male; mean age, 55 years) and partners (33% male; mean age, 59 years) rated the intervention as useful. Paired t-test analyses revealed large effect sizes for reduced sleep disturbances (d = 1.83) and medium effect sizes for cancer-specific distress (d = 0.61) for patients and large effect sizes for depressive symptoms (d = 0.90) for partners. CONCLUSION: Based on these results, the CBMB intervention appears to be acceptable and subjectively useful. In addition, we observed preliminary evidence of quality of life gains in both patients and their partners.

Blood-based biomarkers for precision medicine in lung cancer: precision radiation therapy.

Both tumors and patients are complex and models that determine survival and toxicity of radiotherapy or any other treatment ideally must take into account this variability as well as its dynamic state. The genetic features of the tumor and the host, and increasingly also the epi-genetic and proteomic characteristics, are being unraveled. Multiple techniques, including histological examination, blood sampling, measurement of circulating tumor cells (CTCs), and functional and molecular imaging, can be used for this purpose. However, the effects of radiation on the tumor and on organs at risk (OARs) are also influenced by the applied dose and volume of irradiated tissues. Combining all these biological, clinical, imaging, and dosimetric parameters in a validated prognostic or predictive model poses a major challenge. Here we aimed to provide an objective review of the potential of blood markers to guide high precision radiation therapy. A combined biological-mathematical approach opens new doors beyond prognostication of patients, as it allows truly precise oncological treatment. Indeed, the core for individualized and precision medicine is not only selection of patients, but even more the optimization of the therapeutic window on an individual basis. A holistic model will allow for determination of an individual dose-response relationship for each organ at risk for each tumor in each individual patient for the complete oncological treatment package. This includes, but is not limited to, radiotherapy alone. Individualized dose-response curves will allow for consideration of different doses of radiation and combinations with other drugs to plan for both optimal toxicity and complete response. Insights into the interactions between a multitude of parameters will lead to the discovery of new pathways and networks that will fuel new biological research on target discovery.

Vivekananda Yoga Program for Patients With Advanced Lung Cancer and Their Family Caregivers.

BACKGROUND: The primary purpose of this study was to establish the feasibility of a couple-based Vivekananda Yoga (VKC) intervention in lung cancer patients and caregivers. Secondly, we examined preliminary efficacy regarding quality of life (QOL) outcomes. METHOD: In this single-arm feasibility trial, patients with lung cancer undergoing radiotherapy and their caregivers participated in a 15-session VKC program that focused on the interconnectedness of the dyad. We assessed pre-and post-intervention levels of fatigue, sleep disturbances, psychological distress, overall QOL, spirituality, and relational closeness. We tracked feasibility data, and participants completed program evaluations. RESULTS: We approached 28 eligible dyads of which 15 (53%) consented and 9 (60%) completed the intervention. Patients (mean age = 73 years, 63% female, all stage III) and caregivers (mean age = 62 years, 38% female, 63% spouses) completed a mean of 10 sessions and 95.5% of them rated the program as very useful. Paired t tests revealed a significant increase in patients' mental health (d = 0.84; P = .04) and a significant decrease in caregivers' sleep disturbances (d = 1.44; P = .02). Although not statistically significant, for patients, effect sizes for change scores were medium for benefit finding and small for distress (d = 0.65 and 0.37, respectively). For caregivers, medium effects were found for improvement in physical functioning (d = 0.50). CONCLUSION: This novel supportive care program appears to be safe, feasible, acceptable, and subjectively useful for lung cancer patients and their caregivers and lends support for further study.

Qigong improves quality of life in women undergoing radiotherapy for breast cancer: results of a randomized controlled trial.

BACKGROUND: Radiotherapy may lead to side effects that undermine patients' quality of life (QOL). Although mind-body practices like qigong appear to improve QOL in cancer survivors, little is known about their benefits for patients who are receiving radiotherapy. Thus, in the current randomized controlled trial, the authors examined the efficacy of a qigong intervention on QOL in women with breast cancer during and after treatment. METHODS: Ninety-six women with breast cancer were recruited from a cancer center in Shanghai, China, and were randomized to a qigong group (N = 49) or a waitlist control group (N = 47). Women in the qigong group attended 5 weekly classes over 5 or 6 weeks of radiotherapy. QOL outcomes (ie, depressive symptoms, fatigue, sleep disturbance, and overall QOL) and cortisol slopes were assessed at baseline, during treatment, at the end of treatment, 1 month later, and 3 months later. RESULTS: The mean age of the women was 46 years (range, 25-64 years). Seven percent of women had stage 0 disease, 25% had stage I disease, 40% had stage II disease, and 28% had stage III disease. Fifty-four percent of women underwent mastectomy. Multilevel analyses revealed that women in the qigong group reported less depressive symptoms over time than women in the control group (P = .05). Women who had elevated depressive symptoms at the start of radiotherapy reported less fatigue (P < .01) and better overall QOL (P < .05) in the qigong group compared with the control group, and these findings were clinically significant. No significant differences were observed for sleep disturbance or cortisol slopes. CONCLUSIONS: The current results indicated that qigong may have therapeutic effects in the management of QOL among women who are receiving radiotherapy for breast cancer. Benefits were particularly evident for patients who had preintervention elevated levels of depressive symptoms.

Multimodality treatment of pancreatic cancer with liver metastases using chemotherapy, radiation therapy, and/or Chinese herbal medicine.

OBJECTIVE: To explore the utility of multidisciplinary approaches in the treatment of patients with pancreatic cancer with liver metastases (PCLM). METHODS: From 2002 to 2007, a total of 164 consecutive patients with PCLM treated with chemotherapy, radiation therapy, and/or Chinese herbal medicine were included in this study. Clinical parameters, treatments received, and survival time from initial diagnosis were analyzed. RESULTS: Of the 164 patients, 113 (69%) were men and 51 (31%) were women, with median age of 58 years. One hundred thirty-two patients (80%) had synchronous liver metastases, and 57 patients (35%) had extrahepatic metastases. Overall median survival time of the 164 patients was 4.7 months; 23 (14%) were alive at least 12 months after initial diagnosis of liver metastases. Karnofsky performance status of less than 80, weight loss (>10% within 6 months), ascites, and carbohydrate antigen 19-9 of 1000 U/mL or greater were the most relevant predictors of poor survival. Multivariate analysis showed that chemotherapy and Chinese herbal medicine were protective factors. CONCLUSIONS: Multimodality treatment is well tolerated by patients with PCLM and may be effective in prolonging their survival. Awareness of the implications of these prognostic factors may assist in evaluating the survival potential of patients and selecting the most appropriate treatments.

Electro-acupuncture to prevent prolonged postoperative ileus: a randomized clinical trial.

AIM: To examine whether acupuncture can prevent prolonged postoperative ileus (PPOI) after intraperitoneal surgery for colon cancer. METHODS: Ninety patients were recruited from the Fudan University Cancer Hospital, Shanghai, China. After surgery, patients were randomized to receive acupuncture (once daily, starting on postoperative day 1, for up to six consecutive days) or usual care. PPOI was defined as an inability to pass flatus or have a bowel movement by 96 h after surgery. The main outcomes were time to first flatus, time to first bowel movement, and electrogastroenterography. Secondary outcomes were quality of life (QOL) measures, including pain, nausea, insomnia, abdominal distension/fullness, and sense of well-being. RESULTS: No significant differences in PPOI on day 4 (P = 0.71) or QOL measures were found between the groups. There were also no group differences when the data were analyzed by examining those whose PPOI had resolved by day 5 (P = 0.69) or day 6 (P = 0.88). No adverse events related to acupuncture were reported. CONCLUSION: Acupuncture did not prevent PPOI and was not useful for treating PPOI once it had developed in this population.

Intensity-modulated radiation therapy with concurrent chemotherapy for locally advanced cervical and upper thoracic esophageal cancer.

AIM: To evaluate the dosimetry, efficacy and toxicity of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with locally advanced cervical and upper thoracic esophageal cancer. METHODS: A retrospective study was performed on 7 patients who were definitively treated with IMRT and concurrent chemotherapy. Patients who did not receive IMRT radiation and concurrent chemotherapy were not included in this analysis. IMRT plans were evaluated to assess the tumor coverage and normal tissue avoidance. Treatment response was evaluated and toxicities were assessed. RESULTS: Five- to nine-beam IMRT were used to deliver a total dose of 59.4-66 Gy (median: 64.8 Gy) to the primary tumor with 6-MV photons. The minimum dose received by the planning tumor volume (PTV) of the gross tumor volume boost was 91.2%-98.2% of the prescription dose (standard deviation [SD]: 3.7%-5.7%). The minimum dose received by the PTV of the clinical tumor volume was 93.8%-104.8% (SD: 4.3%-11.1%) of the prescribed dose. With a median follow-up of 15 mo (range: 3-21 mo), all 6 evaluable patients achieved complete response. Of them, 2 developed local recurrences and 2 had distant metastases, 3 survived with no evidence of disease. After treatment, 2 patients developed esophageal stricture requiring frequent dilation and 1 patient developed tracheal-esophageal fistula. CONCLUSION: Concurrent IMRT and chemotherapy resulted in an excellent early response in patients with locally advanced cervical and upper thoracic esophageal cancer. However, local and distant recurrence and toxicity remain to be a problem. Innovative approaches are needed to improve the outcome.

Dose-response relationship in locoregional control for patients with stage II-III esophageal cancer treated with concurrent chemotherapy and radiotherapy.

PURPOSE: To evaluate the correlation between radiation dose and locoregional control (LRC) for patients with Stage II-III unresectable esophageal cancer treated with concurrent chemotherapy and radiotherapy. METHODS AND MATERIALS: The medical records of 69 consecutive patients with clinical Stage II or III esophageal cancer treated with definitive chemoradiotherapy at the University of Texas M. D. Anderson Cancer Center between 1990 and 1998 were retrospectively reviewed. Of the 69 patients, 43 had received < or =51 Gy (lower dose group) and 26 >51 Gy (higher dose group). The median dose in the lower and higher dose groups was 30 Gy (range, 30-51 Gy) and 59.4 Gy (range, 54-64.8 Gy), respectively. Two fractionation schedules were used: rapid fractionation, delivering 30 Gy at 3 Gy/fraction within 2 weeks, and standard fractionation, delivering > or =45 Gy at 1.8-2 Gy/fraction daily. Total doses of <50 Gy were usually given with rapid fractionation. Cisplatin and 5-fluorouracil were administrated to 93% of the patients. RESULTS: The patient characteristic that differed between the two groups was that patients in the lower dose group were more likely to have had weight loss >5% (46.2% vs. 23.3%). The lower dose group had more N1 tumors, but the tumor classification and stage grouping were similar in the two groups. The median follow-up time for all patients was 22 months (range, 2-56 months). Patients in the higher dose group had a statistically significant better 3-year local control rate (36% vs. 19%, p = 0.011), disease-free survival rate (25% vs. 10%, p = 0.004), and overall survival rate (13% vs. 3%, p = 0.054). A trend toward a better distant-metastasis-free survival rate was noted in the higher dose group (72% vs. 59%, p = 0.12). The complete clinical response rate was significantly greater in the higher dose group (46% vs. 23%, p = 0.048). In both groups, the most common type of first failure was persistence of the primary tumor. Significantly fewer patients in the higher dose group had tumor persistence after treatment (p = 0.02). No statistically significant difference was found between the two groups in the pattern of locoregional or distant failure. The long-term side effects of chemoradiotherapy were similar in the two groups, although it was difficult to assess the side effects accurately in a retrospective fashion. On multivariate analysis, Stage II (vs. III) disease and radiation dose >51 Gy were independent predictors of improved LRC, and locoregional failure was an independent predictor of worse overall survival. CONCLUSION: Our data suggested a positive correlation between radiation dose and LRC in the population studied. A higher radiation dose was associated with increased LRC and survival in the dose range studied. The data also suggested that better LRC was associated with a lower rate of distant metastasis. A threshold of tumor response to radiation dose might be present, as suggested by the flattened slope in the high-dose area on the dose-response curve. A carefully designed dose-escalation study is required to confirm this assumption.

Induction chemotherapy improved outcomes of patients with resectable esophageal cancer who received chemoradiotherapy followed by surgery.

PURPOSE: To investigate the effect of induction chemotherapy (CHT) before trimodality therapy on the outcome of patients with resectable cancer of the esophagus. METHODS AND MATERIALS: This retrospective study included 81 consecutive patients with resectable cancer of the esophagus who received neoadjuvant chemoradiotherapy followed by esophagectomy between January 1990 and December 1998 (inclusive). Thirty-nine patients underwent chemoradiotherapy followed by esophagectomy (CHT/RT+S), 42 received additional induction CHT followed by CHT/RT+S (CHT+CHT/RT+S). Of the 81 patients, 47 were entered in institutional or national prospective trials (6 in the CHT/RT+S and 41 in the CHT+CHT/RT+S group). Induction CHT consisted of three courses of 5-fluorouracil (5-FU), cisplatin, and paclitaxel given in 28-day cycles in 37 patients (88.1%). Concurrent CHT was 5-FU and platinum based. The median radiation dose for patients treated with CHT/RT+S was 30 Gy (range, 30-50.4 Gy) delivered in a median of 10 fractions (range, 10-28 fractions) and 45 Gy (range, 30-45 Gy) in a median of 25 fractions (range, 10-25 fractions) for patients treated with CHT+CHT/RT+S. Esophagectomy was performed 6-8 weeks after completion of concurrent chemoradiotherapy. Most patients underwent transthoracic esophagectomy (n = 66, 82.5%). RESULTS: The pretreatment characteristics were well balanced between the two groups except for age. The median follow-up time was 29 months (22 months for the CHT/RT+S group and 38.5 months for the CHT+CHT/RT+S group) for all patients and 49 months for living patients. The actuarial overall survival (OS), disease-free survival (DFS), locoregional control (LRC), and distant metastasis-free survival (DMFS) rate at 5 years for the entire group was 46%, 36.6%, 70.7%, and 53.2%, respectively. Statistically significant differences in the OS, DFS, and LRC rates between the two groups were detected. Specifically, the 5-year OS rate was 22.8% and 71.1% in the CHT/RT+S and CHT+CHT/RT+S group (p = 0.0001), respectively. The 5-year DFS rate was 27.6% and 56.6% in the CHT/RT+S and CHT+CHT/RT+S group (p = 0.003), respectively. The 5-year LRC rate was 64.2% and 85.6% in the CHT/RT+S and CHT+CHT/RT+S group (p = 0.007), respectively. The difference in the DMFS rate between the two groups was statistically significant, with a 2- and 5-year actuarial rate of 63.9% and 51.9%, respectively, in the CHT/RT+S group and 76.9% and 74.1%, respectively, in the CHT+CHT/RT+S group (p = 0.04). The statistically significant differences persisted when patients who received >/=45 Gy in each group were compared. Among those patients, the 5-year OS, DFS, LRC, and DMFS rates were 23.1%, 15.4%, 58.6%, and 39.2%, respectively, for those receiving CHT/RT+S, and 71.4% (p = 0.001), 55.8% (p = 0.0008), 84.6% (p = 0.005), and 77.3% (p = 0.009), respectively, for those receiving CHT+CHT/RT+S. The pathologic complete response (pCR) rate was greater in the CHT+CHT/RT+S group compared with in the CHT/RT+S group (p = 0.008). In univariate analysis, young age, good Karnofsky performance status, Stage II disease, total radiation dose, multiple drug regimen for concurrent CHT, pCR, R0 resection, distant disease progression, and CHT+CHT/RT+S treatment proved to be prognostic factors for OS. Lower esophageal/gastroesophageal junction tumor location, pCR, R0 resection, and CHT+CHT/RT+S treatment were favorable prognostic factors for LRC. Neither the total radiation dose nor multiple drugs for concurrent CHT were negative prognostic factors for LRC. In multivariate analysis, pCR, R0 resection, and treatment with CHT+CHT/RT+S were independent positive predictive factors for OS, and distant recurrences were negative predictive factors for OS. R0 resection, CHT+CHT/RT+S treatment, and lower esophageal/gastroesophageal junction tumor location were positive predictive factors for LRC. The radiation dose was not identified as an independent prognostic factor for either OS or LRC in the multivariate analysis. Meaningful multivariate analysis could not be performed when the multiple drug vperformed when the multiple drug variable was included in the model because of the small number of patients. CONCLUSION: Significantly greater LRC, DFS, OS, and DMFS were found in patients treated with CHT+CHT/RT+S compared with those treated with CHT/RT+S. The pCR rate was significantly higher in the CHT+CHT/RT+S group. Induction CHT was an independent favorable prognostic factor for both LRC and OS for the population included in this study. Our data suggest that a randomized trial comparing CHT+CHT/RT+S and CHT/RT+S is warranted to assess further the merits of this treatment in patients with this currently very lethal cancer.