Docetaxel, Cisplatin, and 5-FU Triplet Therapy as Conversion Therapy for Locoregionally Advanced Unresectable Esophageal Squamous Cell Carcinoma.

BACKGROUND: The standard treatment for locoregionally advanced unresectable esophageal squamous cell carcinoma was radical chemoradiotherapy. However, the prognosis was modest. Emerging evidence showed the concept of induction chemotherapy with a goal of conversion surgery. METHODS: We reviewed the long-term, clinical outcomes and safety data of induction chemotherapy using docetaxel-cisplatin-5FU (DCF) and subsequent definitive treatment, either surgery or radical chemoradiotherapy (CRT), in locally advanced unresectable esophageal cancer in Queen Mary Hospital, Hong Kong. A total of 47 patients (median age 62 years, male: 41 (87.2%)) with locoregionally advanced unresectable esophageal cancer received induction DCF. The response rate was 65.9% (complete/partial response: n = 31). After induction DCF, 24 patients (41.4%) had radical surgery and 7 (14.9%) had definitive CRT. RESULTS: The median overall survival (mOS) was significantly longer in patients received subsequent surgery compared with those with definitive CRT (mOS: 40.2 vs. 9.1 months, hazard ratio 3.33, 95% confidence interval 1.22-9.07, p = 0.02) and no definitive treatment (mOS: 40.2 vs. 6.3 months, hazard ratio 8.51, 95% confidence interval 3.7-19.73, p < 0.001). Patients who received surgery, female, and those with supraclavicular lymph node involvement had a better OS. Twenty-one patients (44.7%) developed grade 3/4 adverse events during induction DCF, and two died after chemotherapy because of trachea-esophageal fistula complicated with sepsis. Eleven patients who had surgery had postoperative complications and none had postoperative mortality. CONCLUSIONS: Induction DCF and subsequent conversion surgery offered a chance of cure with long-term survival benefit and manageable toxicities in patients with locoregionally advanced unresectable esophageal cancer.

Particle beam therapy for nasopharyngeal cancer: A systematic review and meta-analysis.

Background/purpose: A systematic review and meta-analysis were performed to better understand the benefits of particle beam therapy for nasopharyngeal cancer (NPC) treatment. The survival outcomes and toxicity of primary and recurrent NPC patients treated with proton or carbon ion beam therapy were investigated. Method: PubMed, Scopus, and Embase were searched between 1 January 2007 to 3 November 2021. The inclusion and exclusion criteria included studies with either primary or recurrent NPC patients, sample size of ≥10 patients, and proton or carbon ion beam therapy as interventions. Twenty-six eligible studies with a total of 1502 patients were included. We used a random-effect meta-analysis to examine the impact of particle beam therapy on primary NPC patients and qualitatively described the results among recurrent patients. The primary outcome was overall survival (OS), while secondary outcomes included progression-free survival (PFS), local control (LC) and toxicity. Results: The pooled OS at 1-year, 2-year and 3-year and 5-year for primary NPC patients who received particle beam therapy were 96 % (95 % confidence interval (CI) = 92 %-98 %), 93 % (95 % CI = 83 %-97 %), 90 % (95 % CI = 73 %-97 %) and 73 % (95 % CI = 52 %-87 %) respectively. The pooled 1-year and 2-year PFS, and LC for these patients were above 90 %. For locally recurrent NPC patients, the 1-year OS rate ranged from 65 % to 92 %, while the 1-year LC rate ranged from 80 % to 88 %. Both proton and carbon ion beam therapy were generally safe among primary and recurrent patients, with ≥G3 late toxicity rates of 20 % or less. Approximately a 5 % mortality rate was reported among recurrent patients. Conclusions: This systematic review and meta-analysis demonstrated particle beam therapy has great potential in treating NPC, yielding excellent survival outcomes with low toxicity. However, further investigations are needed to assess the long-term outcomes and cost-effectiveness of this newer form of radiotherapy.

Treatment Outcomes of Computer Tomography-Guided Brachytherapy in Cervical Cancer in Hong Kong: A Retrospective Review.

(1) Background: To report the long-term clinical outcomes of computer-tomography (CT)-guided brachytherapy (BT) for locally advanced cervical cancer. (2) Methods: A total of 135 patients with FIGO stage IB-IVA cervical cancer treated with definitive radiotherapy +/- chemotherapy with an IGABT boost at Queen Mary Hospital, Hong Kong, between November 2013 and December 2019 were included. Treatment included pelvic radiotherapy 40 Gy/20 Fr/4 weeks +/- chemotherapy then CT-guided BT (7 Gy × 4 Fr) and a sequential parametrial boost. The primary outcome was local control. Secondary outcomes were pelvic control, distant metastasis-free survival, overall survival (OS) and late toxicities. (3) Results: The median follow-up was 53.6 months (3.0-99.6 months). The five-year local control, pelvic control, distant metastasis-free survival and OS rates were 90.7%, 84.3%, 80.0% and 87.2%, respectively. The incidence of G3/4 long-term toxicities was 6.7%, including proctitis (2.2%), radiation cystitis (1.5%), bowel perforation (0.7%), ureteric stricture (0.7%) and vaginal stenosis and fistula (0.7%). Patients with adenocarcinomas had worse local control (HR 5.82, 95% CI 1.84-18.34, p = 0.003), pelvic control (HR 4.41, 95% CI 1.83-10.60, p = 0.001), distant metastasis-free survival (HR 2.83, 95% CI 1.17-6.84, p = 0.021) and OS (HR 4.38, 95% CI: 1.52-12.67, p = 0.003) rates. Distant metastasis-free survival was associated with HR-CTV volume ≥ 30 cm3 (HR 3.44, 95% CI 1.18-9.42, p = 0.025) and the presence of pelvic lymph node (HR 3.44, 95% CI 1.18-9.42, p = 0.025). OS was better in patients with concurrent chemotherapy (HR 4.33, 95% CI: 1.40-13.33, p = 0.011). (4) Conclusions: CT-guided BT for cervical cancer achieved excellent long-term local control and OS. Adenocarcinoma was associated with worse clinical outcomes. (4) Conclusion: CT-guided BT for cervical cancer achieved excellent long-term local control and OS. Adenocarcinoma was associated with worse clinical outcomes.

Exploratory Study of NPC-0501 Trial: Optimal Cisplatin Dose of Concurrent and Induction/Adjuvant Chemotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma.

PURPOSE: The current recommendation for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) is cisplatin-based induction chemotherapy (IC) or adjuvant chemotherapy (AC) plus concurrent chemoradiotherapy (CRT). However, data on the optimal platinum doses for each phase of combined regimens are lacking. EXPERIMENTAL DESIGN: 742 patients with NPC in the NPC-0501 trial treated with CRT plus IC/AC and irradiated with intensity-modulated radiotherapy (IMRT) were analyzed. The optimal platinum dose to achieve the best overall survival (OS) in the concurrent and induction/adjuvant phases was studied. RESULTS: Evaluation of the whole series shows the optimal platinum dose was 160 mg/m2 in the concurrent and 260 mg/m2 in the induction/adjuvant phase. Repeating the analyses on 591 patients treated with cisplatin throughout (no replacement by carboplatin) confirmed the same results. The cohort with optimal platinum doses in both phases had better OS than the cohort suboptimal in both phases (stage III: 90% vs. 75%; stage IVA-B: 80% vs. 56%, at 5-year). Multivariable analyses confirmed optimal platinum doses in both phases versus suboptimal dose in each phase are significant independent factors for OS, with HR of 0.61 [95% confidence interval (CI), 0.41-0.91] and 0.67 (95% CI, 0.48-0.94), respectively. Treatment sequence was statistically insignificant after adjusting for platinum doses. CONCLUSIONS: Both concurrent and IC/AC are needed for locoregionally advanced NPC, even for patients irradiated by IMRT; the concurrent platinum dosage could be set at ≥160 mg/m2 when coupled with adequate induction/adjuvant dosage at ≥260 mg/m2 (or at least ≥240 mg/m2). To achieve these optimal dosages, IC-CRT at conventional fractionation is favored.

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.

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.

Real-world Scenario: CROSS Regimen as Preoperative Therapy for Oesophageal Squamous Cell Carcinoma.

BACKGROUND: Preoperative chemoradiation (CROSS regimen) has been widely adopted worldwide. The survival advantage imparted is especially impressive for oesophageal squamous cell carcinoma (OSCC). This study aimed at investigating the efficacy of the CROSS regimen in real-world scenario. METHODS: This is a retrospective study of all patients with OSCC intended for preoperative treatment using the CROSS regimen during 2012-2017. Patients were divided into two groups: those within the selection criteria in the CROSS trial and those beyond criteria, namely age > 75 years old, tumour length > 8 cm or clinical M1 stage of lymph node involvement (AJCC 6th edition). Clinical outcome and survival data were compared. RESULTS: Eighty-eight patients were included. There were 46 patients in the "CROSS eligible" group and 42 in the "CROSS ineligible" group. By intention-to-treat, the estimated median survival was 24.2 months vs. 12.7 months, respectively (p = 0.047). The results were much inferior compared to that published in the original CROSS trial. Univariable and multivariable analyses showed tumour length and resectability as independent variables affecting survival. DISCUSSION: In a real-world scenario, the clinical outcome remains suboptimal and the excellent results in the trial setting were not reproducible in this Asian cohort. Patient selection is one key element accountable for the difference. The efficacy of the CROSS regimen may not be adequate for patients with more advanced disease. The optimal multimodal therapy for this group of patients remains undefined.

Revisiting oral fluoropyrimidine with cetuximab in metastatic colorectal cancer: Real-world data in Chinese population.

BACKGROUND: Cetuximab in combination with oral fluoropyrimidine (FP) remains controversial in metastatic colorectal cancer (mCRC). In view of the regional variation in the tolerability of FP, we conducted a retrospective analysis to compare oral FP with infusional FP in combination with cetuximab in Chinese population. AIM: To compare the efficacy and safety profile of cetuximab in combination with oral FP and infusional FP in Chinese population in the real-world setting. METHODS: A retrospective cohort study was done to analyse consecutive patients with Kras wild-type mCRC who received first-line treatment with cetuximab and FP-based chemotherapy in our unit from January 2010 to December 2015. Ninety-five eligible patients were included. The median follow-up of our cohort was 65.0 mo. RESULTS: The median progression-free survival (mPFS) and median overall survival (mOS) of the entire cohort were 9.66 mo (95%CI: 7.72-12.5) and 25.8 mo (95%CI: 18.7-35.6), respectively. Between oral FP and infusional FP, there was no statistical significant difference in the mPFS [9.79 mo (95%CI: 7.49-12.7) vs 9.63 mo (95%CI: 6.34-13.4); P = 0.72] and mOS [25.8 mo (95%CI: 15.2-35.6) vs 26.3 mo (95%CI: 18.7-41.2); P = 0.63]. Grade 3 or above adverse events were reported in 28.4% of patients, being similar with oral and infusional FP, and included 10.5% of neutropenia and 2.1% of diarrhoea events. CONCLUSION: The current analysis demonstrates comparable efficacy and safety profiles of cetuximab in combination with oral and infusional FP in Chinese population. The results expand treatment options for Chinese patients and invite revision of existing treatment guidelines to incorporate oral FP-based chemotherapy plus cetuximab.

Negative plasma Epstein-Barr virus DNA nasopharyngeal carcinoma in an endemic region and its influence on liquid biopsy screening programmes.

BACKGROUND: Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) in endemic regions may have undetectable plasma EBV DNA. METHODS: We prospectively recruited 518 patients with non-metastatic NPC and measured their pre-treatment plasma EBV DNA. The stage distribution and prognosis between pre-treatment plasma EBV DNA-negative (0-20 copies/ml) and EBV DNA-positive (>20 copies/ml) patients following radical treatment were compared. RESULTS: Seventy-eight patients (15.1%) were plasma EBV DNA-negative, and 62 in this subset (12.0%) had 0 copy/ml. Only 23/78 (29.5%) plasma EBV DNA-negative patients with advanced NPC (stage III-IVA) had strong EBV encoded RNA (EBER) positivity (score 3) in their tumours compared to 342/440 (77.7%) EBV DNA-positive patients of the same stages (p < 0.001). Though EBV DNA-negative patients had more early-stage disease (p < 0.001) and smaller volumes of the primary tumour and the positive neck nodes (p < 0.001), they had similar 5-year overall survival and cancer-specific survival to those EBV DNA-positive counterparts by stage. Similar results were also seen when plasma EBV DNA cut-off was set at 0 copy/ml. CONCLUSIONS: Patients with low-volume NPC may not be identified by plasma/serum tumour markers and caution should be taken in its utility as a screening tool for NPC even in endemic regions. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02476669.

The addition of pretreatment plasma Epstein-Barr virus DNA into the eighth edition of nasopharyngeal cancer TNM stage classification.

The eighth edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage classification (TNM) for nasopharyngeal carcinoma (NPC) was launched. It remains unknown if incorporation of nonanatomic factors into the stage classification would better predict survival. We prospectively recruited 518 patients with nonmetastatic NPC treated with radical intensity-modulated radiation therapy ± chemotherapy based on the eighth edition TNM. Recursive partitioning analysis (RPA) incorporating pretreatment plasma Epstein-Barr virus (EBV) DNA derived new stage groups. Multivariable analyses to calculate adjusted hazard ratios (AHRs) derived another set of stage groups. Five-year progression-free survival (PFS), overall survival (OS) and cancer-specific survival (CSS) were: Stage I (PFS 100%, OS 90%, CSS 100%), II (PFS 88%, OS 84%, CSS 95%), III (PFS 84%, OS 84%, CSS 90%) and IVA (PFS 71%, OS 75%, CSS 80%) (p < 0.001, p = 0.066 and p = 0.002, respectively). RPA derived four new stages: RPA-I (T1-T4 N0-N2 & EBV DNA <500 copies per mL; PFS 94%, OS 89%, CSS 96%), RPA-II (T1-T4 N0-N2 & EBV DNA ≥500 copies per mL; PFS 80%, OS 83%, CSS 89%), RPA-III (T1-T2 N3; PFS 64%, OS 83%, CSS 83%) and RPA-IVA (T3-T4 N3; PFS 63%, OS 60% and CSS 68%) (all with p < 0.001). AHR using covariate adjustment also yielded a valid classification (I: T1-T2 N0-N2; II: T3-T4 N0-N2 or T1-T2 N3 and III: T3-T4 N3) (all with p < 0.001). However, RPA stages better predicted survival for PS and CSS after bootstrapping replications. Our RPA-based stage groups revealed better survival prediction compared to the eighth edition TNM and the AHR stage groups.

Management of Nasopharyngeal Carcinoma: Is Adjuvant Therapy Needed?

Nasopharyngeal carcinoma of the undifferentiated histologic subtype is endemic and prevalent in southeast Asia. The dramatic improvement of treatment outcomes and overall prognosis during the past few decades has been attributed to advances in disease screening and diagnosis, diagnostic imaging, radiotherapy techniques, use of combination systemic therapy, and dedicated clinical and biomarker surveillance. The current practice of treating patients with advanced locoregional disease using cisplatin concurrent with conventional fractionated radiotherapy, followed by adjuvant cisplatin and fluorouracil, was established in 1998 when the landmark Intergroup-0099 Study demonstrated a survival benefit with the addition of systemic therapy. There is little doubt regarding the need for concurrent chemotherapy, but there has been uncertainty about the magnitude of the benefit attributed to the adjuvant phase. Furthermore, instead of one-size-fits-all recommendations, it will be ideal if we can tailor adjuvant therapy to high-risk patients only to avoid unnecessary toxicities. In addition, recent evidence suggests that induction chemotherapy before concurrent chemoradiation can achieve better outcomes, especially in distant control, even in the modern era of intensity-modulated radiation therapy. This article provides a comprehensive review of key literature on the current management of locoregionally advanced nasopharyngeal carcinoma and highlights future research directions to unravel these controversies.

The impact of palliative care training for oncologists and integrative palliative service in a public-funded hospital cluster-a retrospective cohort study.

PURPOSE: Oncological care of advanced cancer patients was provided by multiple departments in Hong Kong. One of these departments, the clinical oncology department (COD), introduced systematic palliative care training for its oncologists since 2002. The COD was recognized as a European Society for Medical Oncology (ESMO) Designated Centre of Integrated Oncology and Palliative Care since 2009. This retrospective cohort study aims to review the impact of integrative training and service on palliative care coverage and outcome. METHODS: Clinical information, palliative service provision, and end-of-life outcomes of patients who passed away from lung, colorectal, liver, stomach, or breast cancer in the Hong Kong West public hospital network during July 2015 to December 2015 were collected. RESULTS: A total of 307 patients were analyzed. Around half (49.2%) were attended primarily by COD, and 68.9% received palliative service. There are significantly fewer patients referred to palliative care from other departments (p < 0.001), with only 19.9% of this patient group receiving palliative referral. COD patients had longer palliative coverage before death (median 65 days versus 24 days, p < 0.001), higher chance of receiving end-of-life care at hospice units (36.4 versus 21.2%, p = 0.003), lower ICU admission (0.66 versus 5.1%, p = 0.02), and higher percentage of receiving strong opioid in the last 30 days of life (51.0 versus 28.9%, p < 0.001) compared to other departments. In multivariable analysis, COD being the primary care team (odds ratio 12.2, p < 0.001) was associated with higher palliative care coverage. CONCLUSION: The study results suggested that systematic palliative care training of oncologists and integrative palliative service model was associated with higher palliative service coverage and improved palliative care outcomes.

Prognostication of serial post-intensity-modulated radiation therapy undetectable plasma EBV DNA for nasopharyngeal carcinoma.

Plasma Epstein-Barr virus (EBV) DNA titers have been used to monitor treatment response and provide prognostic information on survival for nasopharyngeal carcinoma (NPC). However, the long-term prognostic role of pretreatment and posttreatment titers after radical contemporaneous radiation therapy remains uncertain. We recruited 260 evaluable patients with non-metastatic NPC treated with radical intensity-modulated radiation therapy (IMRT) with or without adjunct chemotherapy. Plasma EBV DNA titers at baseline and then 8 weeks and 6 months after IMRT were measured. Cox regression models were employed to identify interaction between post-IMRT 8th week and 6th month undetectable titers and 3-year survival endpoints. Concordance indices (Ct) from time-dependent receiver-operating characteristics (TDROC) were compared between patients with post-IMRT undetectable and those with detectable titers. After a median follow-up duration of 3.4 years (range 1.4-4.6 years), patients with post-IMRT 8th week and 6th month undetectable plasma EBV DNA titers enjoyed longer 3-year survival endpoints than those who had detectable titers at the same time points. Post-IMRT 8th week, and more significantly, post-IMRT 6th month undetectable plasma EBV DNA were the only significant prognostic factors of 3-year survival endpoints. Ct values for all 3-year survival endpoints for both post-IMRT 8th week and 6th month undetectable plasma EBV DNA were significantly higher in those with stage IVA-IVB diseases compared to stage I-III counterparts. Early post-IMRT undetectable plasma EBV DNA titers were prognostic of 3-year survival endpoints in patients with non-metastatic NPC. Intensified treatment should be further explored for patients with persistently detectable titers after IMRT.

Dosimetric Predictors of Hypothyroidism After Radical Intensity-modulated Radiation Therapy for Non-metastatic Nasopharyngeal Carcinoma.

AIMS: To investigate dosimetric predictors of hypothyroidism after radical intensity-modulated radiation therapy (IMRT) for non-metastatic nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Patients with non-metastatic NPC treated with radical IMRT from 2008 to 2013 were reviewed. Serum thyroid function tests before and after IMRT were regularly monitored. Univariable and multivariable analyses were carried out for predictors of biochemical and clinical hypothyroidism. RESULTS: In total, 149 patients were recruited. After a median follow-up duration of 3.1 years, 33 (22.1%) and 21 (14.1%) patients developed biochemical and clinical hypothyroidism, respectively. Eight (24.2%) patients who had biochemical hypothyroidism developed clinical hypothyroidism later. Univariable and multivariable analyses revealed that the volume of the thyroid (P=0.002, multivariable), VS60 (the absolute thyroid volume spared from 60 Gy or less) (P<0.001, multivariable) and VS45 (P<0.001, multivariable) of the thyroid were significant predictors of biochemical hypothyroidism. The freedom from biochemical hypothyroidism was longer for those whose VS60 ≥ 10 cm(3) (mean 90.9 versus 62.6 months; P<0.001) and VS45 ≥ 5 cm(3) (mean 91.9 versus 65.2 months; P=0.001). Similarly multivariable analyses revealed that VS60 (P=0.001) and VS45 (P=0.003) were significant predictors of clinical hypothyroidism. The freedom from clinical hypothyroidism was longer for those whose VS60 ≥ 10 cm(3) (91.5 versus 73.3 months; P=0.002) and VS45 ≥ 5 cm(3) (91.5 versus 75.9 months; P=0.007). CONCLUSIONS: VS60 and VS45 of the thyroid should be considered important dose constraints against hypothyroidism without compromising target coverage during IMRT optimisation for NPC.

Global Pattern of Nasopharyngeal Cancer: Correlation of Outcome With Access to Radiation Therapy.

PURPOSE: This study aimed to estimate the treatment outcome of nasopharyngeal cancer (NPC) across the world and its correlation with access to radiation therapy (RT). METHODS AND MATERIALS: The age-standardized mortality (ASM) and age-standardized incidence (ASI) rates of NPC from GLOBOCAN (2012) were summarized, and [1-(ASM/ASI)] was computed to give the proxy relative survival (RS). Data from the International Atomic Energy Agency (IAEA) and the World Bank were used to assess the availability of RT in surrogate terms: the number of RT equipment units and radiation oncologists per million population. RESULTS: A total of 112 countries with complete valid data were analyzed, and the proxy RS varied widely from 0% to 83% (median, 50%). Countries were categorized into Good, Median, and Poor outcome groups on the basis of their proxy RS (<45%, 45%-55%, and >55%). Eighty percent of new cases occurred in the Poor outcome group. Univariable linear regression showed a significant correlation between outcome and the availability of RT: proxy RS increased at 3.4% (P<.001) and 1.5% (P=.001) per unit increase in RT equipment and oncologist per million population, respectively. The median number of RT equipment units per million population increased significantly from 0.5 in the Poor, to 1.5 in the Median, to 4.6 in the Good outcome groups, and the corresponding number of oncologists increased from 1.1 to 3.3 to 7.1 (P<.001). CONCLUSIONS: Nasopharyngeal cancer is a highly treatable disease, but the outcome varies widely across the world. The current study shows a significant correlation between survival and access to RT based on available surrogate indicators. However, the possible reasons for poor outcome are likely to be multifactorial and complex. Concerted international efforts are needed not only to address the fundamental requirement for adequate RT access but also to obtain more comprehensive and accurate data for research to improve cancer outcome.

Association of exon 19 and 21 EGFR mutation patterns with treatment outcome after first-line tyrosine kinase inhibitor in metastatic non-small-cell lung cancer.

BACKGROUND: This study investigated whether there were differential survival outcomes to first-line tyrosine kinase inhibitors (TKI) in patients with metastatic non-small-cell lung cancer harboring different subtypes of exon 19 and exon 21 mutations on epidermal growth factor receptor (EGFR). METHODS: Of 452 patients with stage IIIB and IV non-small-cell lung cancer, 192 patients (42.5%) harbored EGFR mutation and 170 (37.5%) received TKI as first-line treatment. EGFR mutation analysis was performed by direct sequencing. Survival and response outcome were compared among different subtypes of exon 19 and exon 21 EGFR mutations in these 170 patients. RESULTS: Patients harboring exon 19 18-nucleotide deletion (delL747_P753insS) had the shortest median progression-free survival (PFS) (6.5 months), followed by those with 15-nucleotide deletion (delE746_A750) (12.4 months) and mixed insertion/substitution mutations (22.3 months; p = 0.012). However, patients who had exon 19 deletions starting on codon E746 had better median PFS (14.2 months) than those starting on L747 (6.5 months; hazard ratio, 0.445; 95% confidence interval [0.219-0.903]; p = 0.021). Besides, exon 21 L858R derived a longer median PFS than L861R/L861Q (11.4 months versus 2.1 months, respectively; hazard ratio, 0.298; 95% confidence interval [0.090-0.980]; p = 0.034). CONCLUSIONS: Different subtypes of EGFR exon 19 and 21 mutations exhibited differential survival to first-line TKI therapy. Detailed sequence evaluation of exon 19 deletions may provide important prognostic information on survival outcome after TKI.

Comparative analysis of dosimetric parameters of three different radiation techniques for patients with Graves' ophthalmopathy treated with retro-orbital irradiation.

BACKGROUND: We would like to investigate the if IMRT produced better target coverage and dose sparing to adjacent normal structures as compared with 3-dimensional conformal radiotherapy (3DCRT) and lateral opposing fields (LOF) for patients with Graves' ophthalmopathy treated with retro-orbital irradiation. METHODS: Ten consecutive patients diagnosed with Graves' ophthalmopathy were prospectively recruited into this study. An individual IMRT, 3DCRT and LOF plan was created for each patient. Conformity index (CI), homogeneity index (HI) and other dosimetric parameters of the targets and organs-at-risk (OAR) generated by IMRT were compared with the other two techniques. RESULTS: Mann-Whitney U test demonstrated that CI generated by IMRT was superior to that produced by 3DCRT and LOF (p=0.005 for both respectively). Similarly HI with IMRT was proven better than 3DCRT (p=0.007) and LOF (p=0.005). IMRT gave rise to better dose sparing to some OARs including globes, lenses and optic nerves as compared with 3DCRT but not with LOF. CONCLUSIONS: IMRT, as compared with 3DCRT and LOF, was found to have a better target coverage, conformity and homogeneity and dose sparing to some surrounding structures, despite a slight increase but clinically negligible dose to other structures. Dosimetrically it might be a preferred treatment technique and a longer follow up is warranted to establish its role in routine clinical use.

Can the analysis of ERCC1 expression contribute to individualized therapy in nasopharyngeal carcinoma?

PURPOSE: To analyze the expression of excision repair cross-complementation group 1 (ERCC1) protein in predicting the clinical outcome of nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: The histologic specimens of 258 patients with Stage III to IVB nonkeratinizing NPC who were treated with radiotherapy alone (Group I) or concurrent-adjuvant chemoradiotherapy (Group II) were retrieved. Immunostaining on ERCC1 protein was performed. The relationship of ERCC1 expression and clinical outcomes was analyzed. RESULTS: The median ERCC1 score (proportion score of positively stained cells times intensity) was 200 (range, 0-300), and ERCC1 expression was defined as high if the score was above the median. In Group I high-score tumor had a statistically lower locoregional failure-free rate (LRFFR) compared with low-score tumor (p < 0.05) but not distant failure-free rate (DFFR) and overall survival (OS). In Group II no statistically differences were noted in LRFFR, DFFR and OS with regard to the ERCC1 expression. Resistance to cisplatin-containing chemotherapy in high-ERCC1 score tumor was not observed in Group II. Interestingly, low-score tumor in Group I achieved similar local and distant control compared with Group II. Multivariate analysis showed that ERCC1 score was an independent prognostic factor in LRFFR (p < 0.05) and approached statistical significance in failure-free survival (p = 0.08) and OS (p = 0.07). Tumor with high ERCC1 score had a 2-fold (95% confidence interval, 1.02-3.85) increased risk of locoregional failure. This may imply an association of ERCC1 expression with the repair of radiation damage. CONCLUSIONS: High ERCC1 expression predicts poor locoregional control in NPC. Chemotherapy response is not affected by ERCC1 expression. Further validation is required.

Clinical outcomes and patterns of failure after intensity-modulated radiotherapy for nasopharyngeal carcinoma.

PURPOSE: To study and report the clinical outcomes and patterns of failure after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: The treatment outcomes of NPC patients treated with IMRT at Pamela Youde Nethersole Eastern Hospital between 2005 and 2007 were reviewed. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. Statistical analyses were performed on dose coverage and locoregional failures. RESULTS: A total of 193 NPC patients were analyzed; 93% had Stage III/IV disease. Median follow-up was 30 months. Overall disease failure (at any site) developed in 35 patients. Among these, there were 23 distant metastases, 16 local failures, and 9 regional failures. Four of the locoregional failures were marginal. Dose conformity with IMRT was excellent. Patients with at least 66.5 Gy to their target volumes had significantly less locoregional failure. The 2-year local progression-free, regional progression-free, distant metastasis-free, and overall survival rates were 95%, 96%, 90%, and 92%, respectively. CONCLUSIONS: Intensity-modulated radiotherapy provides excellent locoregional control for NPC. Distant metastasis remains the most difficult challenge, and more effective systemic agents should be explored for patients presenting with advanced locoregional diseases.