Pre-treatment amide proton transfer imaging predicts treatment outcome in nasopharyngeal carcinoma.

OBJECTIVE: To investigate the value of pre-treatment amide proton transfer-weighted (APTw) imaging for predicting survival of patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Pre-treatment APTw imaging was performed in 77 NPC patients and the mean, 90th percentile, skewness, and kurtosis of APT asymmetry (APTmean, APT90, APTskewness, and APTkurtosis, respectively) were obtained from the primary tumor. Associations of APTw parameters with locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) after 2 years were assessed by univariable Cox regression analysis and significant APTw parameters, together with age, sex, treatment, and stage as confounding variables, were added to the multivariable model. Kaplan-Meier analysis was used to determine the prognostic significance of patients with high or low APT values based on a threshold value from receiver operating characteristic curve analysis. RESULTS: Locoregional relapse, distant metastases, and disease relapse occurred in 14/77 (18%), 10/77 (13%), and 20/77 (26%) patients, respectively, at a median follow-up of 48.3 (10.6-67.4) months. Univariable analysis showed significant associations of LRRFS with APTskewness (HR = 1.98; p = 0.034), DMFS with APTmean (HR = 2.44; p = 0.033), and APT90 (HR = 1.93; p = 0.009), and DFS with APTmean (HR = 2.01; p = 0.016), APT90 (HR = 1.68; p = 0.009), and APTskewness (HR = 1.85; p = 0.029). In multivariable analysis, the significant predictors for DMFS were APT90 (HR = 3.51; p = 0.004) and nodal stage (HR = 5.95; p = 0.034) and for DFS were APT90 (HR = 1.97; p = 0.010) and age (HR = 0.92; p = 0.014). An APT90 ≥ 4.38% was associated with a significantly poorer DFS at 2 years than APT90 < 4.38% (66% vs. 91%; HR = 4.01; p = 0.005). CONCLUSION: APTw imaging may potentially predict survival in patients with NPC. KEY POINTS: • APTw imaging may provide new markers to predict survival in nasopharyngeal carcinoma. • APT90 is an independent predictor of distant metastases-free survival and disease-free survival. • The APThigh group is at higher risk of disease relapse than the APTlow group.

Amide proton transfer MRI detects early changes in nasopharyngeal carcinoma: providing a potential imaging marker for treatment response.

PURPOSE: To determine if treatment of nasopharyngeal carcinoma (NPC) induces early changes in amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI), and to perform a preliminary evaluation of APTw imaging in response assessment. METHODS: Sixteen patients with NPC planned for treatment with radiotherapy and/or chemotherapy underwent APTw imaging of the primary tumour pre-treatment and 2-week intra-treatment. Difference in pre- and intra-treatment APT mean (APTmean) was compared using the Wilcoxon signed rank test. Differences in APTmean and percentage change (%Δ) in APTmean were compared between responders and non-responders based on the outcome at 6 months, using the Mann-Whitney U test. RESULTS: APTmean decreased in 9/16 (56.3%) and increased in 7/16 (43.7%) with no significant difference between the pre- and intra-treatment APT values for the whole group (p > 0.05). NPC showed response in 11/16 (68.8%) and non-response in 5/11 (31.2%). There were significant differences between the %Δ of responders and non-responders for APTmean (p = 0.01). Responders showed %Δ decrease in APTmean of - 23.12% while non-responders showed a %Δ increase in APTmean of + 102.28%. CONCLUSION: APT value changes can be detected in early intra-treatment. Intra-treatment %Δ APTmean shows potential in predicting short-term outcome.

A cohort study on protocol-based nurse-led out-patient management of post-chemotherapy low-risk febrile neutropenia.

PURPOSE: International guidelines adopt risk stratification approach to manage patients with low-risk febrile neutropenia patients. We developed this out-patient program using shared-care model with professional input and patient empowerment, so as to reduce patients' psychological burden from hospitalization and to improve the cost-effectiveness of management. METHOD: This is a prospective cohort study to compare the efficacy and safeness of the out-patient program when compared with traditional in-patient care. Patients with solid tumors, developed febrile neutropenia with Multinational Association of Supportive Care in Cancer score of at least 21, and good performance status were included. After initial assessment and the first dose of oral antibiotics, patients were observed in the ambulatory center. Stable patients were discharged home after 4 h of observation and nurse counseling. Patients' condition and clinical progress were regularly reviewed by specialist nurses within the following week by telephone and nurse clinic follow-up. The primary objective of the study is success rate, which defined as the resolution of fever and infection, without hospitalization or any change in antibiotics. RESULTS: From September 2014 to December 2016, a total of 38 patients were enrolled. Majority were female with breast cancer (97%). Two patients required hospitalization due to persistent fever. The success rate of the out-patient program was not significantly different from the historical in-patient cohort (94.9 versus 97.4%, p = 0.053). No mortality was observed. Patients' compliance to the program was 100%, to telephone follow-up, nurse clinic visits, and daily temperature record. CONCLUSION: Out-patient management of patients with low-risk febrile neutropenia is effective and safe through implementation of a structured protocol with joint inputs and engagement from clinicians, oncology nurses, and patients.

Nasopharyngeal carcinoma: relationship between invasion of the prevertebral space and distant metastases.

PURPOSE: To identify primary sites of nasopharyngeal carcinoma (NPC) invasion on the staging head and neck magnetic resonance imaging (MRI) that correlate with distant metastases (DM). MATERIALS AND METHODS: Staging head and neck MRI examinations of 579 NPC patients were assessed for primary tumour invasion into 16 individual sites, primary stage (T) and nodal stage (N). Results were correlated with distant metastasis-free survival (DMFS) using the Cox regression, and the diagnostic performance of significant independent markers for DM was calculated. In addition, sites of primary tumour invasion were correlated also with involvement of the first echelon of ipsilateral nodes (FEN+) using logistic regression. RESULTS: Distant metastases were present in 128/579 NPC patients (22.1%) after intensity-modulated radiotherapy (IMRT)/chemo-IMRT and 5-year DMFS was 78.8%. Prevertebral space invasion (PVS+) and N stage, but not T stage, were independent prognostic markers of DMFS (p = 0.016, < 0.001, and 0.433, respectively). Compared to stage N3, PVS invasion had a higher sensitivity (28.1 vs. 68.8%), but lower specificity (90.5 vs. 47.4%) and accuracy (76.7 vs. 48.9%) for correlating patients with DM. PVS invasion, together with parapharyngeal fat space invasion (PPFS+), was also an independent predictive marker of FEN+. CONCLUSION: PVS was the only site of primary tumour invasion that independently correlated with DM, and together with PPFS + was an independent prognostic marker of FEN+, but the low specificity and accuracy of PVS invasion limits its use as a prognostic marker of DM.

Local ablative radiotherapy on oligo-progression while continued on epidermal growth factor receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer patients: A longer cohort.

BACKGROUND: The effect of adding local ablative radiotherapy on oligo-progression while continuing EGFR-TKIs in advanced non-small cell Lung cancer (NSCLC) patients is to be determined. METHODS: Outcomes of patients with stage IV NSCLC harboring EGFR-activating mutations having ≤5 sites of oligo-progression while on EGFR-TKIs and given one to eight fractions of local ablative radiotherapy (LAR) were reviewed from 2012 to 2019. The time of starting first-line EGFR-TKIs to LAR is defined as progression-free survival 1 (PFS1; > one line of prior treatment allowed). The primary endpoint was PFS from LAR to further progression that led to stop of EGFR-TKIs (PFS2). The secondary endpoint was overall survival from LAR (OS). Factors affecting PFS2 and OS were analyzed with Cox regression. RESULTS: There were total 55 eligible patients. The median follow-up time was 13.3 months. Majority (89%) had sensitive mutations (exon 19 deletion and exon 21 L858R mutation). Total number of lesions treated were 75, including lung (n = 45), bone (n = 15), cervical lymph node (n = 1), adrenal (n = 1), and brain (n = 13). The median PFS2 was 6.9 months. The median OS was 25.1 months. On multivariable analysis, it was found that EGFR mutation type (exon 19 deletion / exon 21 L858R mutation vs. other rarer mutations), time from diagnosis to LAR within 70 days, and fewer lines of prior TKIs (1 or 2 vs. 3) had favorable effect on PFS2 (p = 0.006/0.00003; 0.046; 0.001/0.005, respectively). CONCLUSION: LAR is a noninvasive and effective modality in treatment of oligo-progressive diseases for patients with EGFR mutations positive NSCLC while on EGFR-TKIs.

Predictive factors for bleeding carotid artery pseudoaneurysms in patients with previous radiations for head and neck cancers.

BACKGROUND: Bleeding from carotid artery pseudoaneurysms is an emergency condition with high morbidity and mortality. We aimed to identify risk factors predicting pseudoaneurysmal bleeding as the cause of profuse epistaxis in irradiated head and neck cancer patients with suspect carotid blowout or pseudoaneurysms. METHODS: We retrospectively reviewed consecutive patients with history of radiation therapy for head and neck cancers and with nasal, oral or ear bleeding requiring in-patient treatment from hospital database. Pseudoaneurysms were subgrouped into internal carotid artery (ICA) pseudoaneurysms, and external carotid artery (ECA) pseudoaneurysms. The treatment outcomes were evaluated using 30-day mortality rate, recurrent bleeding, and cerebral infarction. RESULTS: There were 41 admissions for suspected carotid blowout or pseudoaneurysms from 1 July 2016 to 30 June 2020 with 17 bleeding pseudoaneurysms identified, including 11 internal carotid arteries (ICA) pseudoaneurysms and 6 external carotid arteries (ECA) pseudoaneurysms. Among ICA pseudoaneurysms, six patients passed Balloon occlusion test with embolization and parent artery occlusion (trapping) of ICA performed, and all ECA pseudoaneurysms were embolized with parent artery occlusion (trapping). Baseline hypertension and hypotension on arrival were predictive for pseudoaneurysmal bleeding. The degree of haemoglobin drop was not significantly different between pseudoaneurysmal bleeding and non-pseudoaneurysmal bleeding (2.1 ± 1.4 g/dL vs. 1.6 ± 1.4 g/dL, p = 0.234). CONCLUSIONS: We identified baseline hypertension and hypotension on arrival as predictive factors for pseudoaneurysmal bleeding in patients with irradiated head and neck cancer. Presence of these risk factors should alert the clinicians to the possibility of carotid pseudoaneurysms.

Durability of the parotid-sparing effect of intensity-modulated radiotherapy (IMRT) in early stage nasopharyngeal carcinoma: A 15-year follow-up of a randomized prospective study of IMRT versus two-dimensional radiotherapy.

BACKGROUND: The durability of improved xerostomia with intensity-modulated radiotherapy (IMRT) in patients with early stage nasopharyngeal carcinoma (NPC) is uncertain. We conducted a long-term prospective assessment of participants treated with IMRT or two-dimensional radiotherapy (2DRT) in a prior randomized study. METHODS: Parent study participants (IMRT, n = 28; 2DRT, n = 28) who were free of second malignancy or recurrence were eligible. Long-term radiotherapy-related toxicities were graded according to the Radiation Therapy Oncology Group (RTOG) criteria. Long-term patient-reported outcomes were assessed by the six-item xerostomia (XQ) and two European Organisation for Research and Treatment of Cancer (EORTC) questionnaires (QLQ-C30, QLQ-H&N35). Overall survival (OS), locoregional relapse-free survival (LRFS), distant relapse-free survival (DRFS), and the rate of symptomatic late complications (SLCs) were estimated for the entire cohort (n = 56). RESULTS: Totally, 21 (IMRT, n = 10; 2DRT, n = 11) patients gave consent and were assessed for an overall median follow-up of 15.5 years. There was significantly less RTOG ≥grade 2 xerostomia with IMRT versus 2DRT (20% vs. 90%; p = 0.001), but no significant difference in XQ scores. Patients in the IMRT arm reported lower mean scores for the "dry mouth" domain of EORTC QLQ-H&N35 (p = 0.02) and showed trends toward better 15-year OS (81.5% vs. 53.8%, p = 0.06), LRFS (70.6% vs. 53.8%, p = 0.38), and DRFS (81.5% vs. 53.8%, p = 0.07). SLCs were more frequent in the 2DRT arm. CONCLUSIONS: The parotid-sparing effect of IMRT in NPC treatment is durable, with significantly less physician- and patient-scored xerostomia at 15 years. IMRT results in better long-term survival and fewer SLCs.

A convolutional neural network combined with positional and textural attention for the fully automatic delineation of primary nasopharyngeal carcinoma on non-contrast-enhanced MRI.

BACKGROUND: Convolutional neural networks (CNNs) have the potential to automatically delineate primary nasopharyngeal carcinoma (NPC) on magnetic resonance imaging (MRI), but currently, the literature lacks a module to introduce valuable pre-computed features into a CNN. In addition, most CNNs for primary NPC delineation have focused on contrast-enhanced MRI. To enable the use of CNNs in clinical applications where it would be desirable to avoid contrast agents, such as cancer screening or intra-treatment monitoring, we aim to develop a CNN algorithm with a positional-textural fully-connected attention (FCA) module that can automatically delineate primary NPCs on contrast-free MRI. METHODS: This retrospective study was performed in 404 patients with NPC who had undergone staging MRI. A proposed CNN algorithm incorporated with our positional-textural FCA module (Aproposed ) was trained on manually delineated tumours (M1st ) to automatically delineate primary NPCs on non-contrast-enhanced T2-weighted fat-suppressed (NE-T2W-FS) images. The performance of Aproposed , three well-established CNNs, Unet (Aunet ), Attention-Unet (Aatt ) and Dense-Unet (Adense ), and a second manual delineation repeated to evaluate human variability (M 2 nd ) were measured by comparing to the reference standard M 1 st to obtain the Dice similarity coefficient (DSC) and average surface distance (ASD). The Wilcoxon rank test was used to compare the performance of Aproposed against Aunet , Aatt , Adense and M 2 nd . RESULTS: Aproposed showed a median DSC of 0.79 (0.10) and ASD of 0.66 (0.84) mm. It performed better than the well-established networks Aunet [DSC =0.75 (0.12) and ASD =1.22 (1.73) mm], Aatt [DSC =0.75 (0.10) and ASD =0.96 (1.16) mm] and Adense [DSC =0.71 (0.14) and ASD =1.67 (1.92) mm] (all P<0.01), but slightly worse when compared to M 2 nd [DSC =0.81 (0.07) and ASD =0.56 (0.80) mm] (P<0.001). CONCLUSIONS: The proposed CNN algorithm has potential to accurately delineate primary NPCs on non-contrast-enhanced MRI.

Integrative Palliative Care Service Model Improved End-of-Life Care and Overall Survival of Advanced Cancer Patients in Hong Kong: A Review of Ten-Year Territory-Wide Cohort.

Background: Integrated palliative care in oncology service has been widely implemented in Hong Kong since 2006. Aim: The study aimed to review its impact on end-of-life outcomes and overall survival (OS) of cancer patients, as well as its utilization of health care resources in the past 10 years. Design: Cancer deaths of all 43 public hospitals of Hong Kong were screened. Setting/Participants: Randomly selected 2800 cancer deaths formed a representative cohort in all seven service clusters of Hospital Authority at four time points (2006, 2009, 2012, and 2015). Individual patient records were thoroughly reviewed. Propensity score-matched (PSM) analysis was employed to compare the survival of patients. Results: Palliative care provision was associated with improved palliative care outcome, including more prescription of strong opioid, fewer cardiopulmonary resuscitations and intensive care unit admissions, and less futile chemotherapy usage in the end-of-life period (all p < 0.001). In the PSM analysis, the median OS in patients with palliative service (5.10 months, 95% confidence interval [CI] 4.52-5.68 months) was significantly better than those without palliative service (1.96 months, 95% CI 1.66-2.27 months). Patients in the palliative care group had more specialist clinic visits (p < 0.001) and longer hospital stay (p < 0.001) in the last six months of life, although the duration of last admission stay at acute general ward was shortened (p < 0.001). Conclusion: Our results suggested palliative care has played a role in the remarkable improvement in end-of-life outcomes and OS. However, current palliative care model relied heavily on hospital resources. Future work is needed to strengthen community care and to build up quality monitoring systems.

Integrated palliative medicine in public oncology: a 10-year review.

OBJECTIVES: The rapid ageing population of Hong Kong has a high demand on oncology and palliative care (PC) service. This study was the first territory-wide assessment in Hong Kong to assess the palliative service coverage in patients with advanced cancer in the past decade. METHODS: Cancer deaths of all 43 public hospitals of Hong Kong were screened. Randomly selected 2800 cancer deaths formed a representative cohort in all seven service clusters of Hospital Authority at 4 time points (2006, 2009, 2012, 2015). Individual patient records were thoroughly reviewed. Predictors of PC coverage was evaluated in univariable and multivariable analyses. RESULTS: From 2006 to 2015, PC coverage improved steadily from 55.4% to 68.9% (p<0.001). Median time of referral to PC service to death was 25 days (IQR: 53). For duration of inpatient PC, the median time was 22 days (IQR: 44) and it was stable over the past 10 years. Median time of referral to outpatient service to death was 74 days (IQR: 144) and there was an improvement observed (p<0.05). The current system was highly heterogeneous that PC varied between 9.8% and 84.8% in different hospitals depending on the PC service infrastructure. Multivariable Cox model identified patients associated with lower PC coverage: male, <50, rapid disease deterioration and staying in hospitals without multidisciplinary team clinic and designated palliative bed support (all p<0.01). CONCLUSION: There was concrete achievement in palliative service development in the past decade. Heterogeneity and late service provision should be addressed in future.

Dynamic Changes of Post-Radiotherapy Plasma Epstein-Barr Virus DNA in a Randomized Trial of Adjuvant Chemotherapy Versus Observation in Nasopharyngeal Cancer.

PURPOSE: To study the dynamic changes in plasma Epstein-Barr virus (pEBV) DNA after radiotherapy in nasopharyngeal cancer (NPC). EXPERIMENTAL DESIGN: We conducted a randomized controlled trial of adjuvant chemotherapy versus observation in patients with NPC who had detectable pEBV DNA at 6 weeks post-radiotherapy. Randomized patients had a second pEBV DNA checked at 6 months post-randomization. The primary endpoint was progression-free survival (PFS). RESULTS: We prospectively enrolled 789 patients. Baseline post-radiotherapy pEBV DNA was undetectable in 573 (72.6%) patients, and detectable in 216 (27.4%) patients, of whom 104 (13.2%) patients were eligible for randomization to adjuvant chemotherapy (n = 52) versus observation (n = 52). The first post-radiotherapy pEBV DNA had a sensitivity of 0.48, specificity of 0.81, area under receiver-operator characteristics curve (AUC) of 0.65, false positive (FP) rate of 13.8%, and false negative (FN) rate of 14.4% for disease progression. The second post-radiotherapy pEBV DNA had improved sensitivity of 0.81, specificity of 0.75, AUC of 0.78, FP rate of 14.3%, and FN rate of 8.1%. Patients with complete clearance of post-radiotherapy pEBV DNA (51%) had survival superior to that of patients without post-radiotherapy pEBV DNA clearance (5-year PFS, 85.5% vs. 23.3%; HR, 9.6; P < 0.0001), comparable with patients with initially undetectable post-radiotherapy pEBV DNA (5-year PFS, 77.1%), irrespective of adjuvant chemotherapy or observation. CONCLUSIONS: Patients with NPC with detectable post-radiotherapy pEBV DNA who experienced subsequent pEBV DNA clearance had superior survival comparable with patients with initially undetectable post-radiotherapy pEBV DNA. Post-radiotherapy pEBV DNA clearance may serve as an early surrogate endpoint for long-term survival in NPC.

External Validation of a Nomogram to Predict Survival and Benefit of Concurrent Chemoradiation for Stage II Nasopharyngeal Carcinoma.

A nomogram was recently published by Sun et al. to predict overall survival (OS) and the additional benefit of concurrent chemoradiation (CCRT) vs. radiotherapy (RT) alone, in stage II NPC treated with conventional RT. We aimed to assess the predictors of OS and to externally validate the nomogram in the IMRT era. We analyzed stage II NPC patients treated with definitive RT alone or CCRT between 2001 and 2011 under the territory-wide Hong Kong NPC Study Group 1301 study. Clinical parameters were studied using the Cox proportional hazards model to estimate OS. The nomogram by Sun et al. was applied with 1000 times bootstrap resampling to calculate the concordance index, and we compared the nomogram predicted and observed 5-year OS. There were 482 patients included. The 5-year OS was 89.0%. In the multivariable analysis, an age > 45 years was the only significant predictor of OS (HR, 1.98; 95%CI, 1.15-3.44). Other clinical parameters were insignificant, including the use of CCRT (HR, 0.99; 95%CI, 0.62-1.58). The nomogram yielded a concordance index of 0.55 (95% CI, 0.49-0.62) which lacked clinically meaningful discriminative power. The nomogram proposed by Sun et al. should be interpreted with caution when applied to stage II NPC patients in the IMRT era. The benefit of CCRT remained controversial.

Pre-treatment intravoxel incoherent motion diffusion-weighted imaging predicts treatment outcome in nasopharyngeal carcinoma.

PURPOSE: To evaluate whether pre-treatment intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can predict treatment outcome after 2 years in patients with nasopharyngeal carcinoma (NPC). METHOD: One hundred and sixty-one patients with newly diagnosed NPC underwent pre-treatment IVIM-DWI. Univariate Cox regression analysis was performed to evaluate the correlation of the mean values of the pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction and apparent diffusion coefficient with local relapse-free survival (LRFS), regional relapse-free survival (RRFS), distant metastases-free survival (DMFS) and disease-free survival (DFS). Significant diffusion parameters, together with staging, age, gender and treatment as confounding factors, were added into a multivariate model. The area under the curves (AUCs) of significant parameters for disease relapse were compared using the Delong test. RESULTS: Disease relapse occurred in 30 % of the patients at a median follow-up time of 52.1 months. The multivariate analysis showed that high D and T-staging were correlated with poor LRFS (p = 0.042 and 0.020, respectively) and poor DFS (p = 0.023 and 0.001, respectively); low D* and high T-staging with poor RRFS (p = 0.020 and 0.033, respectively); and high N-staging with poor DMFS (p = 0.006). D with the optimal threshold of ≥0.68 × 10-3 mm2/s and T-staging showed similar AUCs (AUC = 0.614 and 0.651, respectively; p = 0.493) for predicting disease relapse. CONCLUSION: High D and low D* were predictors of poor locoregional outcome but none of the diffusion parameters predicted DMFS in NPC.

Second primary cancer after intensity-modulated radiotherapy for nasopharyngeal carcinoma: A territory-wide study by HKNPCSG.

OBJECTIVES: Long-term risk of second primary cancer (SPC) after definitive intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) remains unclear. This study aims to evaluate the risk, predictive factors and survival impact of SPC in a large territory-wide cohort of NPC survivors in an endemic region. MATERIALS AND METHODS: In this multicenter study, consecutive NPC patients (n = 3166) who underwent definitive IMRT in all six public oncology centers in Hong Kong between 2001 and 2010 were included. SPC risks were quantified by standardized incidence ratios (SIRs) and absolute excess risks (AERs) estimated from corresponding age-, sex-, and calendar year-specific population cancer incidence data from the Hong Kong Cancer Registry. Predictive factors and SPC-specific mortality were analyzed. RESULTS: Over a median follow-up period of 10.8 years, 290 cases of SPC were observed with a crude incidence of 9.2%. Cancer risk in NPC survivors was 90% higher than that in general population [SIR, 1.9; 95% confidence interval (CI), 1.7-2.2], with an AER of 52.1 (95% CI, 36.8-67.3) per 10,000 person-years at risk. Significant excess cancer risks were observed for oral cavity, sarcoma, oropharynx, paranasal sinus, salivary gland, thyroid, skin and lung. Advanced age, smoking, hepatitis B status, and re-irradiation were independent predictive factors. SPC accounted for 9.4% of all deaths among NPC survivors during the study period, and 10-year SPC-specific mortality was 3.4%. CONCLUSIONS: Second cancer risk after IMRT was substantial among NPC patients. SPC impairs long-term survival, and close surveillance is warranted as part of survivorship care.

A randomized study of olanzapine-containing versus standard antiemetic regimens for the prevention of chemotherapy-induced nausea and vomiting in Chinese breast cancer patients.

OBJECTIVES: Chemotherapy-induced nausea and vomiting (CINV) are distressing symptoms. This randomized study evaluated the antiemetic efficacies of standard antiemetic regimen with/without olanzapine. PATIENTS AND METHODS: Eligible patients were chemotherapy-naive Chinese breast cancer patients who were planned for (neo)adjuvant doxorubicin/cyclophosphamide. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomized to Olanzapine (with olanzapine) or Standard arms (without olanzapine). Patients filled in self-reported diaries and completed visual analogue scales for nausea, as well as Functional Living Index-Emesis questionnaires. Blood profiles including fasting glucose and lipids were monitored. RESULTS: 120 patients were randomized. In Cycle 1 doxorubicin/cyclophosphamide, the Olanzapine arm had significantly higher rates of "Complete Response" than the Standard arm: 65.0% vs 38.3% in the overall period (p = 0.0035), 70.0% vs 51.7% in the acute period (p = 0.0397) and 92.9% vs 74.2% in the delayed period (p = 0.0254). Olanzapine arm also had significantly higher rates of "No significant nausea" and "No nausea" during all 3 time-frames and better QOL. Similar findings were also revealed throughout multiple cycles. Pre-study abnormalities in glucose and lipids occurred in 39.7% and 34.2% of the studied population respectively; there were no differences in these parameters between the two arms at end-of-study assessment. CONCLUSION: The addition of olanzapine to standard aprepitant-based antiemetic regimen provides clinically meaningful improvement in controlling CINV. This was associated with a positive impact on QOL and tolerable toxicity profiles among Chinese breast cancer patients receiving doxorubicin/cyclophosphamide chemotherapy. Further studies on metabolic profiles of breast cancer patients are warranted.

Extranodal extension is a criterion for poor outcome in patients with metastatic nodes from cancer of the nasopharynx.

PURPOSE: Extranodal extension (ENE) is a criterion for advanced nodal staging of oropharyngeal and hypopharyngeal carcinoma. Our aim was to determine if ENE should be a staging criterion for nasopharyngeal carcinoma (NPC). MATERIALS & METHODS: MRI of 546 NPC patients were reviewed retrospectively and in 404/546 (74.0%) with metastatic nodes, the nodes were assessed for ENE (grade 0 = absent; grade 1 = infiltration of surrounding fat; grade 2 = infiltration of muscle/skin), size (total volume), site (unilateral/bilateral and upper/lower neck) and necrosis. Associations between nodal features and regional relapse free survival (RRFS), distant metastases free survival (DMFS) and overall survival (OS) were assessed using cox regression. Differences of survival rates were compared using log-rank test. A p-value of < 0.05 indicates statistical significance. RESULTS: ENE grade was the only determinant of RRFS (p = 0.014) and only independent determinant of DMFS (p = 0.003) and OS (p < 0.001). Grade 2 ENE was associated with significantly poorer RRFS, DMFS and OS compared to grade 0 and 1 (p < 0.05). Addition of grade 2 ENE to N1 and N2 disease showed similar poor RRFS, DMFS and OS to N3 disease (p > 0.05). Compared to the current stage N3 disease, inclusion of grade 2 ENE increased the number of N3 patients from 53/546 (9.7%) to 82/546 (15.0%) with similar hazard ratios for DMFS (6.855 and 7.125, respectively) and OS (3.614 and 4.085, respectively). CONCLUSION: Grade 2 ENE (into muscle and/or skin and/or salivary glands) is an independent indicator of poor outcome and may be considered as a new criterion for N3 nodal disease in NPC.

Analysis of Plasma Epstein-Barr Virus DNA in Nasopharyngeal Cancer After Chemoradiation to Identify High-Risk Patients for Adjuvant Chemotherapy: A Randomized Controlled Trial.

Purpose The contribution of adjuvant chemotherapy after chemoradiation therapy (CRT) in nasopharyngeal cancer (NPC) remains controversial. Plasma Epstein-Barr virus (EBV) DNA is a potential biomarker of subclinical residual disease in NPC. In this prospective, multicenter, randomized controlled trial, we used plasma EBV DNA to identify patients with NPC at a higher risk of relapse for adjuvant chemotherapy. Patients and Methods Eligible patients with histologically confirmed NPC of Union for International Cancer Control stage IIB to IVB, adequate organ function, and no locoregional disease or distant metastasis were screened by plasma EBV DNA at 6 to 8 weeks after radiotherapy (RT). Patients with undetectable plasma EBV DNA underwent standard surveillance. Patients with detectable plasma EBV DNA were randomly assigned to either adjuvant chemotherapy with cisplatin and gemcitabine for six cycles (arm 1) or observation (arm 2). Patients were stratified for primary treatment (RT v CRT) and stage (II/III v IV). The primary end point was relapse-free survival (RFS). Results Seven hundred eighty-nine patients underwent EBV DNA screening. Plasma EBV DNA was undetectable in 573 (72.6%) and detectable in 216 (27.4%); 104 (13.2%) with detectable EBV DNA were randomly assigned to arms 1 (n = 52) and 2 (n = 52). After a median follow-up of 6.6 years, no significant difference was found in 5-year RFS rate between arms 1 and 2 (49.3% v 54.7%; P = .75; hazard ratio for relapse or death, 1.09; 95% CI, 0.63 to 1.89). The level of post-RT plasma EBV DNA correlated significantly with the hazards of locoregional failure, distant metastasis, and death. Conclusion In patients with NPC with detectable post-RT plasma EBV DNA, adjuvant chemotherapy with cisplatin and gemcitabine did not improve RFS. Post-RT plasma EBV DNA level should be incorporated as the selection factor in future clinical trials of adjuvant therapy in NPC.

Induction Chemotherapy plus Concurrent Chemoradiotherapy in Endemic Nasopharyngeal Carcinoma: Individual Patient Data Pooled Analysis of Four Randomized Trials.

Purpose: Because of the uneven geographic distribution and small number of randomized trials available, the value of additional induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) remains controversial. This study performed an individual patient data (IPD) pooled analysis to better assess the precise role of IC + CCRT in locoregionally advanced NPC.Experimental Design: Four randomized trials in endemic areas were identified, representing 1,193 patients; updated IPD were obtained. Progression-free survival (PFS) and overall survival (OS) were the primary and secondary endpoints, respectively.Results: Median follow-up was 5.0 years. The HR for PFS was 0.70 [95% confidence interval (CI), 0.56-0.86; P = 0.0009; 9.3% absolute benefit at 5 years] in favor of IC + CCRT versus CCRT alone. IC + CCRT also improved OS (HR = 0.75; 95% CI, 0.57-0.99; P = 0.04) and reduced distant failure (HR = 0.68; 95% CI, 0.51-0.90; P = 0.008). IC + CCRT had a tendency to improve locoregional control compared with CCRT alone (HR = 0.70; 95% CI, 0.48-1.01; P = 0.06). There was no heterogeneity between trials in any analysis. No interactions between patient characteristics and treatment effects on PFS or OS were found. After adding two supplementary trials to provide a more comprehensive overview, the conclusions remained valid and were strengthened. In a supplementary Bayesian network analysis, no statistically significant differences in survival between different IC regimens were detected.Conclusions: This IPD pooled analysis demonstrates the superiority of additional IC over CCRT alone in locoregionally advanced NPC, with the survival benefit mainly associated with improved distant control. Clin Cancer Res; 24(8); 1824-33. ©2018 AACR.

Treatment of stage IV(A-B) nasopharyngeal carcinoma by induction-concurrent chemoradiotherapy and accelerated fractionation.

PURPOSE: To explore a more effective strategy for treating nasopharyngeal carcinoma with extensive locoregional disease. METHODS AND MATERIALS: Between October 1998 and January 2003, 49 patients with Stage IV(A-B) disease infiltrating or abutting neurologic structures were treated with induction-concurrent chemotherapy and accelerated radiotherapy (RT). A combination of cisplatin and 5-fluorouracil was used in the induction phase and single-agent cisplatin in the concurrent phase. All patients were irradiated with conformal techniques at 2 Gy/fraction, six daily fractions weekly, to a total dose of 70 Gy. RESULTS: Although 92% of patients had one or more acute toxicities Grade 3 or worse, 96% completed the whole course of RT, and 92% had five or more cycles of chemotherapy. The great majority of toxicities were uneventful, but 1 patient died of neutropenic sepsis. With a median follow-up of 3.1 years, 20 patients had failure at one or more sites and 15 patients died. The 3-year locoregional and distant failure-free rate was 77% and 75%, respectively, and the overall survival rate was 71%. At last follow-up, 27% of patients had developed late Grade 3 or worse toxicity (24% were hearing impairments), but none had radiation-induced neurologic damage. CONCLUSION: The current strategy achieved encouraging results for this poor prognostic group, and confirmation of the therapeutic gain by a prospective randomized trial is warranted.

Induction chemotherapy with cisplatin and gemcitabine followed by accelerated radiotherapy and concurrent cisplatin in patients with stage IV(A-B) nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to evaluate the efficacy and toxicity of cisplatin plus gemcitabine as induction chemotherapy in advanced nasopharyngeal carcinoma (NPC). METHODS: Thirty-seven patients with stage IV(A-B) NPC were treated with 3 cycles of cisplatin plus gemcitabine (cisplatin 80 mg/m(2) on day 1; gemcitabine 1250 mg/m(2) on days 1 and 8) 3-weekly as induction chemotherapy, followed by another 3 cycles of concurrent cisplatin (100 mg/m(2) on day 1) 3-weekly with accelerated radiotherapy (RT) at 70 Gy in 2-Gy fractions, 6 daily fractions per week. RESULTS: The overall response rate to induction chemotherapy was > 90%, and side effects other than uncomplicated hematologic toxicities were uncommon. All patients completed RT, with 92% receiving > or = 5 cycles of chemotherapy. At a median follow-up of 2.9 years, the 3-year overall survival (OS) and disease-free survival (DFS) rates were 76% and 63%, respectively. CONCLUSIONS: Cisplatin plus gemcitabine is a well-tolerated, effective, and convenient induction chemotherapy regimen and warrants further studies to confirm its benefit in advanced NPC.