Patterns of care and survival of Chinese glioblastoma patients in the temozolomide era: a Hong Kong population-level analysis over a 14-year period.

Background: The aim of this study is to address the paucity of epidemiological data regarding the characteristics, treatment patterns and survival outcomes of Chinese glioblastoma patients. Methods: This was a population-level study of Hong Kong adult (>18 years) Chinese patients with newly diagnosed histologically confirmed glioblastoma between 2006 and 2019. The age standardized incidence rate (ASIR), patient-, tumor- treatment-related characteristics, overall survival (OS) as well as its predictors were determined. Results: One thousand and ten patients with a median follow-up of 10.0 months were reviewed. The ASIR of glioblastoma was 1.0 per 100 000 population with no significant change during the study period. The mean age was 57 + 14 years. The median OS was 10.6 months (IQR: 5.2-18.4). Independent predictors for survival were: Karnofsky performance score >80 (adjusted OR: 0.8; 95% CI: 0.6-0.9), IDH-1 mutant (aOR: 0.7; 95% CI: 0.5-0.9) or MGMT methylated (aOR: 0.7; 95% CI: 0.5-0.8) glioblastomas, gross total resection (aOR: 0.8; 95% CI: 0.5-0.8) and temozolomide chemoradiotherapy (aOR 0.4; 95% CI: 0.3-0.6). Despite the significant increased administration of temozolomide chemoradiotherapy from 39% (127/326) of patients in 2006-2010 to 63% (227/356) in 2015-2019 (P-value < .001), median OS did not improve (2006-2010: 10.3 months vs 2015-2019: 11.8 months) (OR: 1.1; 95% CI: 0.9-1.3). Conclusions: The incidence of glioblastoma in the Chinese general population is low. We charted the development of neuro-oncological care of glioblastoma patients in Hong Kong during the temozolomide era. Although there was an increased adoption of temozolomide chemoradiotherapy, a corresponding improvement in survival was not observed.

Targeted destruction of cancer stem cells using multifunctional magnetic nanoparticles that enable combined hyperthermia and chemotherapy.

Cancer stem cells (CSCs) have been implicated in cancer recurrence and therapy resistance. Therefore, a CSC-targeted therapy that disrupts the maintenance and survival of CSCs may offer an effective approach in killing tumor cells in primary tumors and preventing the metastasis caused by CSCs. Nanoparticles (NPs)-based thermotherapy and/or chemotherapy are promising therapeutic methods for cancer treatment. Methods: A silica-based multifunctional NP system was present, which encapsulated a chemotherapeutic agent and magnetic cores and coated with a specific antibody against the lung CSCs. The efficacy of this novel therapeutic strategy was systematically studied both in vitro and in vivo by simultaneous activating the combined thermotherapy and chemotherapy via CSC-targeted NPs. Results: These NPs were systematically administered and activated for targeted chemotherapy and thermotherapy by using an externally applied alternating magnetic field (AMF). The antibody-modified NPs targeted to lung CSCs with enhanced cellular uptake in vitro and extended accumulation in tumor in vivo. Up to 98% of lung CSCs was killed in vitro with 30-min application of AMF, due to the combined effects of hyperthermia and chemotherapeutic drug treatment. In in vivo models, this combined therapy significantly suppressed tumor growth and metastasis in lung CSC xenograft-bearing mice, with minimal side effects and adverse effects. Conclusion: With good biocompatibility and targeting capability, the nanodrug delivery system may offer a promising clinical platform for the combined thermotherapy and chemotherapy. This work demonstrated the feasibility of developing multifunctional nanomedicine targeting CSCs for effective cancer treatment.

Living with chemotherapy-induced peripheral neuropathy: Uncovering the symptom experience and self-management of neuropathic symptoms among cancer survivors.

PURPOSE: The study aimed at uncovering the symptom experience of neurotoxicity, self-adopted approaches and perspectives in managing chemotherapy-induced peripheral neuropathic (CIPN) symptoms in a sample of Chinese cancer survivors. METHODS: A qualitative descriptive study was used to explore individual experiences. A purposive sample of 12 female participants experiencing CIPN was invited to semi-structured interviews who were part of a larger prospective observational study investigating the natural progression and risk factors of CIPN. Textual interview data were managed in NVivo. Content analysis was used. RESULTS: Participants were aged 41-64 years and experienced moderate to severe neuropathic symptoms from 5 to 23 months after completion of a six-cycle chemotherapy regimens at reported during the interviews. Four categories emerged from the qualitative data, namely, (1) experience come to reality: characteristics of CIPN symptoms, (2) disruptions and perceived threat: ability to perform activities and resume work, (3) re-establishing an 'at least satisfactory level of well-being', and (4) views of and approaches in managing neuropathic symptoms. CONCLUSIONS: The characteristics of CIPN symptoms causing disruptions in functional and/or psychosocial well-being from the patients' perspectives and the self-help strategies used to manage symptoms showed a need to provide quality multidisciplinary supportive care, focusing on restoring functional and psychosocial well-being, and enhancing knowledge about symptom assessment and evidence-based strategies for empowering cancer survivors to cope with this complex symptom.

Chemoresistant lung cancer stem cells display high DNA repair capability to remove cisplatin-induced DNA damage.

BACKGROUND AND PURPOSE: The persistence of lung cancer stem cells (LCSCs) has been proposed to be the main factor responsible for the recurrence of lung cancer as they are highly resistant to conventional chemotherapy. However, the underlying mechanisms are still unclear. EXPERIMENTAL APPROACH: We examined the cellular response of a human LCSC line to treatment with cisplatin, a DNA-damaging anticancer drug that is used extensively in the clinic. We compared the response to cisplatin of LCSCs and differentiated LCSCs (dLCSCs) by determining the viability of these cells, and their ability to accumulate cisplatin and to implement genomic and transcription-coupled DNA repair. We also investigated the transcription profiles of genes related to drug transport and DNA repair. KEY RESULTS: LCSCs were found to be more stem-like, and more resistant to cisplatin-induced cytotoxicity than dLCSCs, confirming their drug resistance properties. LCSCs accumulated less cisplatin intracellularly than dLCSCs and showed less DNA damage, potentially due to their ability to down-regulate AQP2 and CTR1. The results of the transcription-coupled repair of cisplatin-DNA cross-links indicated a higher level of repair of DNA damage in LCSCs than in dLCSCs. In addition, LCSCs showed a greater ability to repair cisplatin-DNA interstrand cross-links than dLCSCs; this involved the activation of various DNA repair pathways. CONCLUSIONS AND IMPLICATIONS: Our results further clarify the mechanism of cisplatin resistance in LCSCs in terms of reduced cisplatin uptake and enhanced ability to implement DNA repairs. These findings may aid in the design of the next-generation of platinum-based anticancer drugs.

Circulating Epstein-Barr virus DNA in serum of patients with lymphoepithelioma-like carcinoma of the lung: a potential surrogate marker for monitoring disease.

PURPOSE: The purpose of this work was to study the sera of patients with lymphoepithelioma-like carcinoma (LELC) of the lung for circulating EBV DNA. EXPERIMENTAL DESIGN: Prospectively collected serum samples from five female patients with advanced, inoperable LELC of the lung were measured for free circulating EBV DNA using a quantitative PCR technique. EBV-encoded small RNA (EBER)-1 was assayed in serial serum samples of three of the five patients, either from the start or during the initial phase of chemotherapy/radiotherapy until their terminal event or last follow-up. There was only a single-point sample for analysis in the fourth and fifth patients. Six other patients with LELC of the lung were also retrospectively identified, and their sera were tested for EBER-1 at either the first visit plus the last follow-up visit (n = 2), the first visit only (n = 2), or the last follow-up visit only (n = 2). RESULTS: Prospectively collected serum samples from five patients and retrospectively collected serum samples from two patients who had clinical disease at initial serum measurement showed detectable levels of EBER-1. Retrospectively collected serum samples from four patients with no clinical disease had negative sera. There is consistent correlation between the clinical response to treatment and subsequent clinical course of LELC and serum EBER-1 levels in the three prospective patients with longitudinal serum monitoring. CONCLUSIONS: This study shows for the first time that free EBV DNA can be detected in the serum of patients with LELC of the lung and further suggests the feasibility of its use for monitoring response to therapy in advanced cases.

Reirradiation of nasopharyngeal carcinoma with intracavitary mold brachytherapy: an effective means of local salvage.

PURPOSE: To assess the role of intracavitary mold brachytherapy in salvaging local failure of nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: The outcomes of 118 consecutive NPC patients with local failure treated with mold brachytherapy between 1989 and 1996 were retrospectively reviewed. Eleven patients received additional external radiotherapy. RESULTS: All molds were tailor-made, and the whole procedure was performed under local anesthesia. Pharyngeal recess dissection was routinely performed to allow direct contact of the radioactive source with the pharyngeal recess, a common site of local failure. Initially, the molds were preloaded with 192Ir wires, but since 1992, the sources have been manually afterloaded; the mold has also been redesigned for better conformity, ease of insertion, and radiation safety. Using brachytherapy alone, 50-55 Gy was given for recurrence in 4-7 days; for persistence, 40 Gy was administered. The overall complete remission rate was 97%. The rates of 5-year local control, relapse-free survival, disease-specific survival, overall survival, and major complication were 85%, 68.3%, 74.8%, 61.3%, and 46.9%, respectively. Major complications included nasopharyngeal necrosis with headache, necrosis of cervical vertebrae with atlantoaxial instability, temporal lobe necrosis, and palsy of the cranial nerves. The afterloaded mold was as effective as the preloaded version, but with fewer complications. CONCLUSIONS: Intracavitary mold brachytherapy was effective in salvaging NPC with early-stage local persistence or first recurrence.

Papillary thyroid carcinoma: prognostic factors and the role of radioiodine and external radiotherapy.

PURPOSE: To evaluate the role of radioiodine and external radiotherapy treatment in papillary thyroid carcinoma (PTC). METHODS AND MATERIALS: This is a retrospective study of 842 patients with the diagnosis of PTC registered from 1960 to 1997 at the Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong. The mean follow-up was 9.2 years. The stage distribution according to UICC/AJCC TNM staging was as follows: 58.6%, Stage I; 9.6%, Stage II; 26.1%, Stage III; 2.3%, Stage IV; and 3.4%, not stated. RESULTS: The 10-year cause-specific survival (CSS) rates were as follows: Stage I, 99.8%; Stage II, 91.8%; Stage III, 77.4%; and Stage IV, 37.1%. Multivariate analysis showed that the statistically significant poor prognostic factors for CSS were as follows: age older than 45, postoperative gross locoregional (LR) residual disease, distant metastasis (DM) at presentation, and lack of radioactive iodine (RAI) treatment. In patients with no DM and no postoperative LR disease, adjuvant RAI ablation reduced both LR failure (RR [relative risk] = 0.29) and DM (RR = 0.2), although the CSS was not affected. In the subgroup of T1N0 M0 disease, no patient with RAI treatment had a relapse. External radiotherapy reduced the risk of LR failure to 0.35. Subgroup analysis revealed that external radiotherapy was particularly effective in increasing the probability of LR control of disease in patients with gross postoperative LR disease (RR = 0.36). CONCLUSIONS: Both RAI and external radiotherapy were effective treatment in PTC. Total or near-total thyroidectomy followed by RAI treatment appears to result in the best outcome. External radiotherapy to improve LR control is indicated in patients with gross postoperative residual disease. Treatment should be individualized for patients with T1N0 M0 disease.

Follicular thyroid carcinoma: prognostic factors and the role of radioiodine.

BACKGROUND: The objective of this study was to investigate the patterns of recurrence, various prognostic factors, and the role of radioiodine in the treatment of patients with follicular thyroid carcinoma (FTC). METHODS: The clinical outcomes of 215 patients with FTC who were treated at a single institution were analyzed retrospectively. The mean follow-up was 10.8 years. RESULTS: The actuarial rates of cause specific survival (CSS), locoregional (LR) control, and freedom from distant metastasis (DM) at 10 years were 81%, 83%, and 72.3%, respectively. The independent prognostic factors for survival were metastasis at presentation (relative risk [RR], 47.7), radioiodine (RAI) treatment (RR, 0.25), extrathyroidal extension (RR, 3.8), and the postoperative absence of macroscopic disease in the neck region (RR, 0.06). In patients who were treated with RAI, both the LR failure rate (RR, 0.24) and the mortality rate (RR, 0.25) were reduced to about 25%. Subgroup analysis revealed that RAI improved the survival of patients with DM at presentation (RR, 0.17) and improved the LR control rate in patients who had no DM at presentation (RR, 0.13). For patients who underwent total thyroidectomy with negative resection margins, RAI significantly reduced the rate of LR recurrence (RR, 0.05). Patients with the minimally invasive type of FTC had a good prognosis. The 10-year rates for CSS, LR control, and freedom from DM were 97.6%, 100%, and 90.6%, respectively. The prognosis of patients with frankly invasive FTC was much poorer. The 10-year rates for CSS, LR control, and freedom from DM were 66.7%, 100%, and 45%, respectively. CONCLUSIONS: RAI is an effective treatment for patients with FTC. It was associated with improved survival rates and fewer recurrences.

Differentiated thyroid carcinoma in childhood and adolescence-clinical course and role of radioiodine.

BACKGROUND: Differentiated thyroid carcinoma (DTC) in childhood has a good prognosis despite a high incidence of relapse. The use of radioactive iodine (RAI) has not been well established. PROCEDURE: This is a review of 60 patients less than 21 years of age; mean follow-up was 14 years. RESULTS: Patients had a higher relapse rate with papillary thyroid carcinoma (PTC) than with follicular thyroid carcinoma (FTC): 24.5 vs. 9.1%. Compared with 997 patients with age > or = 21, patients <21 years of age had a higher female to male ratio (7.6 vs. 3.9), higher incidence of nodal metastasis (45 vs. 28%), and lung metastasis (15 vs. 7.8%), and improved 10-year cause-specific survival (CSS) (98.3 vs. 89.5%). The 10-year rates of CSS, local-regional failure-free survival (LRFFS), and distant metastasis failure-free survival (DMFFS) for the young patients were 98.3, 79.3, and 90.7%, respectively. In patients with no distant metastasis at presentation, RAI improved 10-year LRFFS (71.9 vs. 86.5%; P = 0.04). At last follow-up, 10 of 12 patients (80%) with local-regional (LR) relapse and five of nine patients (55.6%) with distant metastasis were rendered disease-free. No patient has experienced a second malignancy. CONCLUSIONS: Prognosis of DTC in young patients was good. Patients with LR relapse and distant metastasis had a high rate of remission after treatment. RAI treatment can reduce the rate of LR relapse in patients with no distant metastasis and result in complete remission in half of those with distant metastasis. No patient experienced a second malignancy.

Differentiated thyroid carcinoma: comparison between papillary and follicular carcinoma in a single institute.

PURPOSE: To compare and contrast the clinical presentation and treatment outcome of patients with papillary and follicular thyroid carcinoma and to study the pattern of practice of treatment of differentiated thyroid carcinoma in Hong Kong. METHOD: The clinical presentation and treatment outcomes were reviewed for 1057 patients with differentiated thyroid cancers who were treated at the Queen Elizabeth Hospital, Hong Kong, from 1960 to 1997. Eight hundred forty-two patients had papillary thyroid carcinomas (PTC), and 215 had follicular thyroid carcinomas (FTC). The mean follow-up was 9.2 years. RESULTS: The differences in the clinical factors of PTC to FTC were as follows: PTC had a higher incidence (3.9:1); these patients were younger at presentation (median age, 44 vs 49), showed a higher female-male ratio (4.5 vs 2.9) and smaller primary tumor size (median 2 cm vs 3.5 cm), and a higher incidence of multifocal disease (28.3% vs 18.1%), extrathyroidal extension (39.4% vs 14%), and more lymph node metastases (33.3% vs 12.1%). The incidence of distant metastases was higher for patients with FTC (28.8% vs 8.9%), and cause-specific survival rates were lower (p =.001). The locoregional control rates were not significantly different (p =.2). The 10-year cause-specific survival, freedom from distant metastasis, and locoregional failure figures for PTC compared with FTC were 92.1% vs 81%, 90.8% vs 72.3%, and 78.5% vs 83%. CONCLUSIONS: Although patients with PTC tend to have more advanced locoregional disease compared with those with FTC, the likelihood of locoregional control is similar, and the probability of cure is better.

Papillary microcarcinoma of the thyroid-Prognostic significance of lymph node metastasis and multifocality.

BACKGROUND: It is known that patients with papillary microcarcinoma (PMC) of the thyroid gland have a very favorable prognosis. The rising incidence of PMC among papillary thyroid carcinoma (PTC) necessitates the identification of prognostic factors and the formulation of treatment protocols. METHODS: The authors conducted a retrospective analysis of 203 patients with PMC who were diagnosed on or before 1999 and were treated at the Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong. RESULTS: The cause specific survival, locoregional (LR) failure free survival, and distant metastases failure free survival rates at 10 years were 100%, 92.1%, and 97.1%, respectively. Five patients had lung metastases; 2 patients died of their metastases 12.9 years and 14.8 years after diagnosis, and 3 patients achieved clinical remission after radioiodine (RAI) treatment. Twelve patients had LR recurrences. Patients with LR recurrence were highly salvageable with a combination of surgery, RAI treatment, and external radiotherapy; all but one (who refused treatment) were alive without disease at last follow-up. Multivariate analyses did not reveal any independent prognostic factor for survival. The risk of cervical lymph node (LN) recurrence increased 6.2-fold (P = 0.01) and 5.6-fold (P = 0.02) when LN metastases and multifocal disease were present at diagnosis. RAI ablation reduced the LN recurrence rate to 0.27 (P = 0.04). The presence of LN metastasis increased the rate of distant metastasis 11.2-fold (P = 0.03). Age was not a significant factor in predicting disease recurrence or survival. Subdivision by tumor sizes 5 mm did not affect the outcome, but no patient with tumors