Concurrent-Adjuvant Chemoradiation Therapy for Stage III-IVB Nasopharyngeal Carcinoma-Exploration for Achieving Optimal 10-Year Therapeutic Ratio.

PURPOSE: This is an updated combined analysis of 2 randomized studies (NPC-9901 and NPC-9902 trials) to evaluate the 10-year outcome attributed to the addition of concurrent-adjuvant chemotherapy for advanced locoregional nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Eligible patients with stage III-IVB nonkeratinizing NPC were randomly assigned to radiation therapy alone (RT: 218 patients) or chemoradiation therapy (CRT: 223 patients) using 3 cycles of cisplatin (100 mg/m2) concurrent with RT, followed by 3 cycles of cisplatin (80 mg/m2) and fluorouracil (1000 mg/m2/day for 4 days). All of the patients were irradiated with conventional fractionation to ≥66 Gy. The median follow-up was 13.9 years. RESULTS: Intention-to-treat analysis confirmed that the CRT group achieved significant improvement in 10-year failure-free rate (FFR: 62% vs 52%, P = .016), progression-free survival rate (PFS: 56% vs 44%, P = .008), and overall survival rate (OS: 60% vs 50%, P = .044). There was no significant increase in overall late toxicity rate (51% vs 48%, P = .34) or noncancer deaths (19% vs 16%, P = .52). Exploratory studies showed no difference in disease control between 2 or 3 cycles of concurrent cisplatin; however, patients given 3 concurrent cycles had a significant increase in hearing impairment (40% vs 24%, P = .017). Only those who continued to receive 2 or more cycles of adjuvant cisplatin-fluorouracil achieved significant improvement in distant control (73% vs 65%, P = .037) and maximal survival gain. CONCLUSION: The addition of concurrent cisplatin plus adjuvant cisplatin-fluorouracil could significantly improve overall survival and disease control without incurring a significant increase in late toxicity or noncancer deaths. Exploratory analyses suggested that both the concurrent and the adjuvant phases contributed to tumor control. Furthermore, the number of concurrent cycles could be reduced from 3 to 2 cycles in order to achieve a similar survival benefit without incurring an excessive increase in hearing impairment. This is a useful hypothesis that warrants further validation.

Factors predicting patient satisfaction in women with advanced breast cancer: a prospective study.

BACKGROUND: The present study (1) examined patient satisfaction with care over the first year following the diagnosis of advanced breast cancer and (2) tested if unmet health system and information needs, physical symptom distress, and psychological distress predicted patient satisfaction. METHODS: Prospective study of 213 Chinese women with advanced breast cancer assessed while awaiting or receiving initial chemotherapy (baseline), then again at 1.5-, 3-, 6-, and 12-months post-baseline. Health system and information unmet (HSI) needs, psychological distress, physical symptom distress, and patient satisfaction were assessed at baseline; patient satisfaction was reassessed at each follow-up assessment. Latent growth curve analysis assessed changes in patient satisfaction over the 12 months follow-up; hierarchical multiple regression analysis tested if baseline health system information needs, physical symptom distress, anxiety and depression predicted patient satisfaction at one-year post-baseline. RESULTS: The level of patient satisfaction was high and did not change significantly over time. Only HSI needs (ß = - 0.27, p < 0.005) significantly associated with baseline patient satisfaction. Patient satisfaction at one-year post-baseline was predicted by HSI needs (ß = - 0.26, p < 0.005), Anxiety (ß = 0.23, p < 0.05) and Depression (ß = - 0.28, p < 0.005), adjusting for the effect of baseline patient satisfaction (ß = 0.22, p < 0.005). CONCLUSIONS: Unmet health information needs and greater depressive symptoms at initial treatment phased predicted subsequent poorer patient satisfaction. This highlights a need to reinforce the importance of patient-centered care model in managing advanced breast cancer.

Treatment outcomes of nasopharyngeal carcinoma in modern era after intensity modulated radiotherapy (IMRT) in Hong Kong: A report of 3328 patients (HKNPCSG 1301 study).

PURPOSE: To evaluate treatment outcomes, failure patterns and late toxicities in patients with nasopharyngeal carcinoma (NPC) treated by intensity modulated radiotherapy (IMRT) in 6 public hospitals in Hong Kong over a 10-year period from 2001 to 2010. MATERIAL AND METHODS: Eligible patients were identified through the Hong Kong Cancer Registry data base. Clinical information was retrieved and verified by oncologists working in the individual centers. Treatment details, survival outcomes and late toxicities were analyzed. RESULTS: A total of 3328 patients were recruited. The median follow-up time was 80.2 months. The 8-year actuarial overall survival (OS), local failure-free survival (LFFS), regional failure-free survival (RFFS), distant failure free survival (DFFS), progression-free survival (PFS) for the whole group was 68.5%, 85.8%, 91.5%, 81.5% and 62.6% respectively. Male gender, older age, advanced T and N stage were adverse prognostic factors for OS, DFFS and PFS, whereas use of chemotherapy in form of concurrent chemo-irradiation (CRT), neoadjuvant + CRT, or CRT + adjuvant chemotherapy were favorable prognostic factors for OS and PFS. The local control was adversely affected by advanced T stage. N stage remained as the single adverse prognostic factor for regional control. Distant metastasis was the commonest site of failure. CONCLUSION: IMRT is an effective treatment for NPC with excellent overall loco-regional control. Distant metastasis is the major site of failure. Concurrent chemotherapy with cisplatin has an established role in NPC patients treated by IMRT.

A multicenter, phase 3, randomized trial of concurrent chemoradiotherapy plus adjuvant chemotherapy versus radiotherapy alone in patients with regionally advanced nasopharyngeal carcinoma: 10-year outcomes for efficacy and toxicity.

BACKGROUND: Concurrent-adjuvant chemoradiotherapy (CRT) became a recommended treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) with the first report of a significant survival benefit from the Intergroup 0099 study. However, data on late toxicities are lacking. Previous reports from the current NPC-9901 trial have raised concerns about a failure to improve overall survival (OS) because of an inadequate impact on distant control and increases in toxicities/noncancer deaths. Validation of the long-term therapeutic ratio is needed. METHODS: In this phase 3, randomized trial, patients with nonkeratinizing NPC (stage T1-4/N2-3/M0) were randomly assigned to radiotherapy alone (176 patients) or to CRT (172 patients) with concurrent cisplatin followed by adjuvant cisplatin plus fluorouracil. RESULTS: The early findings of significant improvements in tumor control were maintained: the CRT group achieved significantly higher 10-year overall failure-free (62% vs 50%; P = .01) and progression-free survival rates (56% vs 42%; P = .006) because of superior locoregional control (87% vs 74%; P = .003), whereas the impact on distant control remained insignificant (68% vs 65%; P = .24). The initial differences in toxicities diminished with longer follow-up: 52% versus 47% at 10 years for late toxicities (P = .20), 4.1% versus 2.8% for deaths due to treatment toxicity, and 15.1% versus 13.1% for deaths due to incidental/unknown causes. The OS rate for the CRT group reached statistical superiority at 10 years (62% vs 49%; P = .047). CONCLUSIONS: Long-term results have confirmed that CRT can significantly improve OS without excessive late toxicities for patients with regionally advanced NPC. However, more potent therapy is needed for improving distant control, especially for patients with stage IVA/B disease. Cancer 2017;123:4147-4157. © 2017 American Cancer Society.

Goal adjustment influence on psychological well-being following advanced breast cancer diagnosis.

OBJECTIVE: A diagnosis of advanced breast cancer (ABC) challenges a woman's ambitions. This longitudinal study explored (1) if goal adjustment disposition influenced psychological adjustment patterns among women with ABC and (2) if dispositional hope and optimism moderate effects of goal adjustment on psychological adjustment. METHODS: One hundred ninety three out of 225 women with ABC were assessed while they were awaiting/receiving initial chemotherapy, then again at 6 weeks, 3 months, 6 months, and 12 months post-baseline. Goal disengagement, goal reengagement, optimism, hope, and psychological adjustment (anxiety, depression, and positive affect) were assessed at baseline; psychological adjustment was reassessed at each follow-up. Latent growth curve modeling was used to examine the change of psychological adjustment and test the study objectives. RESULTS: High goal disengagement, low reengagement, and high optimism were associated with lower initial anxiety, while high goal disengagement and optimism predicted a slower rate of change in anxiety. High goal disengagement, reengagement, and optimism were associated with lower initial depression. High goal reengagement, optimism, and hope were associated with initial positive affect scores, while optimism predicted its rate of change. Optimism moderated the effect of goal disengagement on anxiety and depression, whereas hope moderated the effect of goal reengagement on positive affect. CONCLUSION: Goal disengagement and reengagement are two relatively independent processes influencing psychological well-being. These findings will help clinicians to tailor specific interventions to help women coping with the diagnosis of ABC.

The evolution of supportive care needs trajectories in women with advanced breast cancer during the 12 months following diagnosis.

PURPOSE: This longitudinal study examined if the evolution of supportive care needs differed over the first year following the diagnosis of advanced breast cancer and examined factors differentiating these trajectories. METHODS: Two hundred twenty-eight of 276 Chinese women with advanced breast cancer were assessed while they were awaiting or receiving initial chemotherapy, then again at 6 weeks, 3 months, 6 months, and 12 months post-baseline. Supportive care needs (SCNS-34-Ch), psychological distress (Hospital Anxiety and Depression scale), symptom distress (MSAS-Ch), and patient satisfaction (PSEQ-9) were assessed at baseline; supportive care needs were reassessed at each follow-up assessment. Latent growth mixture modeling explored if trajectories differed within each of four need domains: health system, information, and patient support (HSIPS); psychological; physical daily living (PDL); and sexuality needs. Logistic regression identified factors predicting trajectory patterns. RESULTS: Two distinct trajectories were identified for HSIPS and sexuality need domains and three distinct trajectories for psychological and physical daily living need domains. Most women showed stable low levels of HSIPS (78.9 %), psychological (82.4 %), PDL (83.7 %), and sexuality (97.4 %) supportive care needs. One in five and one in eight women showed high initial supportive care needs in HSIPS and psychological and PDL domains, respectively. With the exception of sexuality needs, trajectory patterns were predicted by physical symptom distress. Women in the high-decline group reported greater physical symptom distress. CONCLUSIONS: Most Chinese women with advanced breast cancer showed low stable supportive care needs. Physical symptom distress predicted high supportive care needs. Interventions should focus on optimizing symptom assessment and management.

Real-time monitoring and control on deep inspiration breath-hold for lung cancer radiotherapy--combination of ABC and external marker tracking.

PURPOSE: In this article, the breath-hold and gating concepts were combined for application of lung cancer radiation treatment. The tumor movement was immobilized based on deep inspiration breath hold (DIBH), in which the breath-hold consistency and stability were monitored by infrared (IR) tracking and controlled by gating with a predefined threshold. The authors' goal is to derive the benefits from both techniques, namely, the minimized treatment margin and the known advantages of deep inspiration. The efficacy of the technique in terms of tumor immobility and treatment setup accuracy was evaluated in the study. METHODS: Fourteen patients who were diagnosed with non small cell lung cancer were included in this study. The control of tumor immobility was investigated interfractionally and intrafractionally. The intrabreath-hold tumor motion was devised based on the external marker movement, in which the tumor-marker correlation was studied. The margin of the planning target volume (PTV) was evaluated based on two factors: (1) The treatment setup error accounts for the patient setup and interbreath-hold variations and (2) the intrabreath-hold tumor motion in which the residual tumor motion during irradiation was studied. RESULTS: As the result of the study, the group systematic error and group random error of treatment setup measured at the isocenter were 0.2(R) +/- 1.6, 1.0(A) +/- 2.0, and 0.3(S) +/- 1.5 mm in the left-right (LR), anterior-posterior (AP), and caudal-cranial (CC) directions, respectively. The Pearson correlation coefficient were 0.81 (LR), 0.76 (AP), and 0.85 (CC) mm and suggest tendency in linear correlation of tumor and marker movement. The intrabreath-hold tumor was small in all directions. The group PTV margins of 3.8 (LR), 4.6 (AP), and 4.8 (CC) mm were evaluated to account for both setup errors and residual tumor motion during irradiation. CONCLUSIONS: The study applies the DIBH technique in conjunction with IR positional tracking for tumor immobilization and treatment setup localization. The technique not only proved to be reliable in terms of good tumor immobility and accurate treatment positioning but also to be potentially useful for dose escalation treatment as regarding of the substantially reduced PTV margin and minimizing radiation toxicity from the fully expanded lung volume.

Whole-field simultaneous integrated-boost intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma.

PURPOSE: To retrospectively review the outcomes of our patients with newly diagnosed nondisseminated nasopharyngeal carcinoma treated with intensity-modulated radiotherapy using a whole-field simultaneous integrated-boost technique. METHODS AND MATERIALS: A total of 175 patients treated with WF-SIB between mid-2004 and 2005 were eligible for study inclusion. The distribution of disease by stage was Stage IA in 10.9%, Stage IIA in 2.3%, Stage IIB in 21.7%, Stage III in 41.1%, Stage IVA in 14.9%, and Stage IVB in 9.1%. Of the 175 patients, 2 (1.2%), 10 (5.7%), and 163 (93.1%) had World Health Organization type I, II, and III histologic features, respectively. We prescribed 70 Gy, 60 Gy, and 54 Gy delivered in 33 fractions within 6.5 weeks at the periphery of three planning target volumes (PTV; PTV70, PTV60, and PTV54, respectively). Of the 175 patients, 46 with early T-stage disease received a brachytherapy boost, and 127 with advanced local or regional disease received chemotherapy. RESULTS: The median follow-up period was 34 months. The overall 3-year local failure-free survival, regional failure-free survival, distant failure-free survival, and overall survival rate was 93.6%, 93.3%, 86.6%, and 87.2%, respectively. Cox regression analysis showed Stage N2-N3 disease (p = .029) and PTV (p = .024) to be independent factors predicting a greater risk of distant failure and poor overall survival, respectively. Grade 3 acute mucositis/pharyngitis occurred in 23.4% of patients, and Stage T4 disease was the only significant predictor of mucositis/pharyngitis (p = .021). CONCLUSION: Whole-field simultaneous integrated-boost intensity-modulated radiotherapy with a dose >70 Gy achieved excellent locoregional control, without an excess incidence of severe, acute mucositis/pharyngitis, in the present study. Strategies for using such highly conformal treatment for patients with a large tumor and late N-stage disease are potential areas of investigation for future studies.

Hypofractionated stereotactic radiotherapy for medically inoperable stage I non-small cell lung cancer--report on clinical outcome and dose to critical organs.

We report 20 cases using hypofractionation stereotactic radiotherapy in medically inoperable stage I non-small cell lung cancer with dose escalation of 45-54 Gy prescribed at 85 or 90% isodose level in 3-4 fractions. Two-year local control and cancer-specific survival were 94.7 and 77.6%, respectively, with minimal toxicity. Though, large fraction size can be safely given to peripheral lung tumors, normal tissue tolerance to hypofractionated radiotherapy to esophagus, trachea, main bronchi, aorta and heart remains unknown. Therefore we also reported the maximum point doses to these critical organs to contribute information to extend this technique to more centrally located lung tumors in future.