Addressing the risk and management of cardiometabolic complications in prostate cancer patients on androgen deprivation therapy and androgen receptor axis-targeted therapy: consensus statements from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology.

Background: Androgen deprivation therapy (ADT) is the foundational treatment for metastatic prostate cancer (PCa). Androgen receptor (AR) axis-targeted therapies are a new standard of care for advanced PCa. Although these agents have significantly improved patient survival, the suppression of testosterone is associated with an increased risk of cardiometabolic syndrome. This highlights the urgency of multidisciplinary efforts to address the cardiometabolic risk of anticancer treatment in men with PCa. Methods: Two professional organizations invited five urologists, five clinical oncologists, and two cardiologists to form a consensus panel. They reviewed the relevant literature obtained by searching PubMed for the publication period from April 2013 to April 2023, to address three discussion areas: (i) baseline assessment and screening for risk factors in PCa patients before the initiation of ADT and AR axis-targeted therapies; (ii) follow-up and management of cardiometabolic complications; and (iii) selection of ADT agents among high-risk patients. The panel convened four meetings to discuss and draft consensus statements using a modified Delphi method. Each drafted statement was anonymously voted on by every panelist. Results: The panel reached a consensus on 18 statements based on recent evidence and expert insights. Conclusion: These consensus statements serve as a practical recommendation for clinicians in Hong Kong, and possibly the Asia-Pacific region, in the management of cardiometabolic toxicities of ADT or AR axis-targeted therapies in men with PCa.

A territory-wide real-world efficacy and toxicity analysis of abiraterone acetate versus docetaxel in 574 Asian patients with metastatic hormone-sensitive prostate cancer.

INTRODUCTION: Abiraterone acetate (ABI) or docetaxel (DOC), in addition to androgen-deprivation therapy (ADT), are current treatment options for metastatic hormone-sensitive prostate cancer (mHSPC). No randomized head-to-head trial has compared these 2 mHSPC treatments, and real-world data regarding their outcomes in Asian patients are lacking. PATIENTS AND METHODS: The medical records of mHSPC patients who began upfront ABI or DOC treatment in addition to ADT at seven public oncology centers in Hong Kong between 2015 and 2021 were reviewed. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), prostate-specific antigen (PSA) response, and toxicities. Kaplan-Meier and multivariate Cox regression analyses were performed. RESULTS: A total of 574 patients were included, of whom 419 received DOC and 155 received ABI. The median follow-up duration was 22.4 (DOC group: 23.8; ABI group: 17.3) months. The ABI group demonstrated significantly better PFS than the DOC group (not reached vs. 15.1 months: hazard ratio = 0.37; 95% confidence interval = 0.28-0.50; P < .001). No significant OS difference was observed (P = .58). Failure to achieve a ≥ 90% decline in PSA level at 3 months and failure to achieve an undetectable PSA nadir were each associated with unfavorable PFS and OS. Patients who received DOC had a higher rate of febrile neutropenia, whereas those who received ABI had higher rates of grade ≥ 3 hypokalemia and elevated alanine transaminase. Treatment discontinuation due to toxicities was more common in the DOC (3.6%) than the ABI (0.6%) group. CONCLUSION: In Asian mHSPC patients, upfront ABI + ADT was associated with better PFS than DOC + ADT, with no significant OS difference. PSA kinetics may help stratify the prognosis for treatment intensification. Toxicity profiles were different, with a higher rate of toxicity-related treatment discontinuation in the DOC group.

Real-world experience of cabozantinib in Asian patients with advanced renal cell carcinoma following treatment with VEGFR tyrosine kinase inhibitors and/or immune-checkpoint inhibitors.

Background: There is a lack of real-world data on the use of cabozantinib in Asian patients with metastatic renal cell carcinoma. Methods: We conducted a retrospective study to investigate the toxicity and efficacy of cabozantinib in this patient population who progressed on tyrosine kinase inhibitors and/or immune-checkpoint inhibitors from six oncology centres in Hong Kong. The primary endpoint was the incidence of serious adverse events (AEs) attributed to cabozantinib. Secondary safety endpoints included dose reductions and AE-led treatment terminations. Secondary effectiveness endpoints included overall survival, progression-free survival, and objective response rate. Results: A total of 24 patients were included. Half received cabozantinib as a third-line or later-line treatment, whilst 50% received prior immune-checkpoint inhibitors, primarily nivolumab. Overall, 13 (54.2%) patients reported at least one cabozantinib-related AE of grades 3-4. The most commonly reported AEs were hand-foot skin reactions (9; 37.5%) and anaemia (4; 16.7%). Fifteen (65.2%) patients required dose reductions. Three patients discontinued treatment because of AEs. The median progression-free survival and overall survival were 10.3 months and 13.2 months, respectively; 6 (25%) patients achieved partial responses, and 8 (33.3%) achieved stable disease. Conclusion: Cabozantinib was generally well tolerated and efficacious in Asian patients with metastatic renal cell carcinoma who were heavily pretreated.

Ethnic Pharmacogenomic Differences in the Management of Asian Patients with Metastatic Prostate Cancer.

Progression to metastatic disease occurs in about half of all men who develop prostate cancer (PC), one of the most common cancers in men worldwide. Androgen deprivation therapy has been the mainstay therapy for patients with metastatic PC (mPC) since the 1940s. In the last decade, there has been unprecedented advancement in systemic therapies, e.g., taxane, androgen-signalling pathway inhibitors, and biomarker-driven targeted therapies for various stages of disease, resulting in overall survival improvement. Adding to ongoing controversies over how best to treat these patients is the recognition that ethnicity may influence prognosis and outcomes. This review discusses recent evidence for the impacts of Asian ethnicity specifically, which includes environmental, sociocultural, and genetic factors, on the approach to pharmacological management of mPC. Clear inter-ethnic differences in drug tolerability, serious adverse events (AEs), and genetic heterogeneity must all be considered when dosing and scheduling for treatment, as well as designing future precision studies in PC.

Prevention of docetaxel-associated febrile neutropenia with primary granulocyte colony-stimulating factor in Chinese metastatic hormone-sensitive and castration-resistant prostate cancer patients.

INTRODUCTION: Asian prostate cancer (PC) patients are particularly susceptible to docetaxel-related febrile neutropenia (FN). We evaluated primary granulocyte colony-stimulating factor (GCSF) for preventing FN in Chinese patients with metastatic hormone-sensitive PC (mHSPC) and castration-resistant PC (mCRPC). PATIENTS AND METHODS: Data from two cohorts of 377 Chinese patients with mHSPC (100; 26.5%) and mCRPC (277; 73.5%) treated with docetaxel at six public oncology centres were analysed with multivariate regression. Primary GCSF prophylaxis was defined as administration within 5 days of starting docetaxel. The primary outcome was FN within 21 days of the first docetaxel cycle (1st FN). RESULTS: Primary GCSF was given to 71 (18.8%) patients. FN occurred in 61 patients (16.2%) including 37 (9.8%) during the first cycle. Among patients who developed 1st cycle FN (n = 37) or not (n = 340), 2 and 69 received primary GCSF (5.4 vs. 20.3%, P = .03). Primary GCSF was associated with an overall reduced risk of 1st cycle FN (odds ratio [OR] = 0.22; 95% confidence interval [CI]: 0.05-0.96, P = .04), and similar trends were observed in the mHSPC (OR = 0.36, P = .35) and mCRPC (OR = 0.16, P = .08) subgroups. Poor Eastern Cooperative Oncology Group performance status (>1) was associated with an increased risk of 1st FN (OR = 3.90; 95% CI: 1.66-9.13, P = .002). CONCLUSIONS: To alleviate the risk of docetaxel-related FN, primary GCSF prophylaxis is suggested for Asian mCRPC and mHSPC patients, particularly those with poor performance status.

Consensus statements on the management of metastatic renal cell carcinoma from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology 2019.

BACKGROUND: To establish a set of consensus statements for the management of metastatic renal cell carcinoma, a total of 12 urologists and clinical oncologists from two professional associations in Hong Kong formed an expert consensus panel. METHODS: Through a series of meetings and using the modified Delphi method, the panelists presented recent evidence, discussed clinical experiences, and drafted consensus statements on several areas of focus regarding the management of metastatic renal cell carcinoma. Each statement was eventually voted upon by every panelist based on the practicability of recommendation. RESULTS: A total of 46 consensus statements were ultimately accepted and established by panel voting. CONCLUSIONS: Derived from recent evidence and expert insights, these consensus statements were aimed at providing practical guidance to optimize metastatic renal cell carcinoma management and promote a higher standard of clinical care.

A Territory-wide, Multicenter, Age- and Prostate-specific Antigen-matched Study Comparing Chemohormonal Therapy and Hormonal Therapy Alone in Chinese Men With Metastatic Hormone-sensitive Prostate Cancer.

BACKGROUND: There is a lack of real-world data regarding the treatment outcomes of chemohormonal therapy versus hormonal therapy alone in Chinese men with metastatic hormone-sensitive prostate cancer. PATIENTS AND METHODS: We conducted a territory-wide, multicenter, age- and prostate-specific antigen (PSA)-matched cohort study comparing chemohormonal therapy and hormonal therapy alone in Chinese men with metastatic hormone-sensitive prostate cancer. Patient and disease characteristics were reviewed. The primary outcome was PSA progression-free survival. Secondary outcomes included clinical progression-free survival and castration resistance-free survival. Kaplan-Meier and multivariate Cox regression analyses were performed. RESULTS: From January 2015 to July 2016, 32 Chinese men with metastatic hormone-sensitive prostate cancer were treated with chemohormonal therapy, and they were matched to 32 Chinese men who were treated with hormonal therapy alone. Patient and disease characteristics were similar between the 2 groups. The chemohormonal therapy group had a significantly better PSA progression-free survival (P = .001) and castration resistance-free survival (P = .002) than the hormonal therapy group. There was no significant difference in the clinical progression-free survival between the 2 groups. Upon multivariate Cox regression analyses, the use of chemohormonal therapy was significantly associated with a longer time to PSA progression (hazard ratio, 0.31; 95% confidence interval, 0.31-0.73; P = .008) and a longer time to castration resistance (hazard ratio, 0.38; 95% confidence interval, 0.17-0.83; P = .015), but was not associated with clinical progression. CONCLUSIONS: The use of chemohormonal therapy could prevent PSA progression and the development of castration resistance when compared with hormonal therapy alone in Chinese men with metastatic hormone-sensitive prostatic cancer.

Survival Outcomes, Prostate-specific Antigen Response, and Tolerance in First and Later Lines of Enzalutamide Treatment for Metastatic Castration-resistant Prostate Cancer: A Real-World Experience in Hong Kong.

BACKGROUND: The present study retrospectively evaluated the efficacy and safety of enzalutamide in different lines of metastatic castration-resistant prostate cancer (mCRPC) treatment in a real-world setting. PATIENTS AND METHODS: The clinical records of patients with mCRPC treated with enzalutamide between August 2015 and October 2017 were retrieved from all 7 public oncology centers in Hong Kong and reviewed. The primary endpoint was progression-free survival (PFS) in first (1L), second (2L), and third or fourth lines (3L or 4L) of CRPC treatment. Secondary endpoints included overall survival (OS), prostate-specific antigen (PSA) response, and tolerance. RESULTS: Among a total of 117 patients (median age of 73 years [range, 52-90 years]), 34 (29.1%), 57 (48.7%), and 26 (19.3%) patients had enzalutamide as their 1L (chemo-naive), 2L (post-docetaxel or -abiraterone), and 3L or above treatment options. The overall PSA response rates were 43.6%, and were 73.5%, 35.1%, and 19.2% for 1L, 2L, and 3L or 4L treatment, respectively. PFS and OS were significantly associated with the line of treatment in the univariate survival analysis (1L/2L/3L and 4L; PFS, 7.1/3.9/2.2 months; OS, not reached/15.8/7.4 months; both P = .0002) but not in the multivariate analysis. The observed incidence of any fatigue (grade 1 or 2, 54.7%; grade 3 or 4, 9.4%) was much higher than reported in the AFFIRM (A Study Evaluating the Efficacy and Safety of the Investigational Drug MDV3100 [ClinicalTrials.gov Identifier: NCT00974311]) (any grade, 34%) and PREVAIL (A Multinational Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy And Safety Study Of Oral Mdv3100 In Chemotherapy-naïve Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy [ClinicalTrials.gov Identifier: NCT00974311]) (any grade, 36%) trials; as well, grade ≥ 2 fatigue was significantly associated with 3L or 4L treatment (P = .01 in both univariate and multivariate analyses). CONCLUSION: In the real-life setting, there was a higher incidence of enzalutamide-related fatigue than reported in the trials. Earlier lines of enzalutamide treatment were associated with longer PFS and OS, more frequent PSA response, and less fatigue.

Preliminary efficacy and tolerability of chemohormonal therapy in metastatic hormone-naïve prostate cancer: The first real-life experience in Asia.

INTRODUCTION: A substantial survival benefit with chemohormonal therapy has been proven by the CHAARTED and STAMPEDE studies, and this clinical approach has emerged as the standard of care for patients with metastatic hormone-naïve prostate cancer (mHSPC). However, because its clinical efficacy and tolerability in Asian patients remains uncertain, this study aims to evaluate preliminary results of its use in Hong Kong. METHODS: The clinical records of mHSPC patients treated with chemohormonal therapy from all six public oncology centers in Hong Kong between January 2015 and July 2016 were reviewed. Time to castration-resistant prostate cancer (CRPC), treatment-related complications, prostate-specific antigen (PSA) response and the time to PSA nadir were assessed. RESULTS: A total of 32 patients (median age, 66 years) were treated with chemohormonal therapy in the review period. After median follow-up time of 11.4 months, the median time to CRPC and time to PSA nadir were 19.5 months and 7 months, respectively. PSA response (>50% drop in PSA level from baseline) was achieved in all patients and the median maximal PSA response was 99.6%. The rates of grade 3 or 4 febrile neutropenia, neutropenia and anemia were 12.5%, 40.6% and 3.1%, respectively. CONCLUSION: Early efficacy with chemohormonal therapy in Asian mHSPC patients was comparable to the pivotal study and biochemical response is promising. The high frequency of hematologic toxicities in Asian patients highlights the importance of proper patient selection and pre-emptive use of granulocyte colony-stimulating factor.

Differences in clinical outcome between docetaxel and abiraterone acetate as the first-line treatment in chemo-naïve metastatic castration-resistant prostate cancer patients with or without the ineligible clinical factors of the COU-AA-302 study.

BACKGROUND: This study aimed to compare the efficacy of abiraterone acetate (AA) versus docetaxel (T) as first-line treatment in chemo-naïve metastatic castration-resistant prostate cancer (mCRPC) patients with or without the ineligible factors of the COU-AA-302 study (presence of visceral metastases, symptomatic disease, and/or Eastern Cooperative Oncology Group performance status ≥ 2). MATERIALS AND METHODS: The clinical records of chemo-naïve mCRPC patients who received AA in six public oncology centers or T in two of these centers between 2003 and 2014 were reviewed. The survival time was compared among four subgroups of patients: those with ineligible factors administered AA (Group Ineligible-AA) or T (Group Ineligible-T), and those without ineligible factors and administered AA (Group Eligible-AA) or T (Group Eligible-T). RESULTS: During the study period, we identified 115 mCRPC patients who received AA or T, among whom 29, 36, 29, and 21 patients were classified as Groups Ineligible-AA, Ineligible-T, Eligible-AA, and Eligible-T, respectively. Both Group Ineligible-AA and Group Eligible-AA had significantly longer progression-free survival (PFS) and similar overall survival (OS) as Group Ineligible-T and Group Eligible-T (Ineligible, PFS: 6.3 vs. 5.9 months, P = 0.0234, OS: 7.8 vs. 15.7 months, P = 0.1601; Eligible, PFS: 9.8 vs. 5.6 months, P = 0.0437, OS: 20.5 vs. 18.2 months, P = 0.7820). CONCLUSIONS: Compared to T, AA treatment resulted in longer PFS and similar OS in chemo-naïve mCRPC patients, irrespective of the presence of ineligible factors, suggesting that the initial treatment by AA may still be beneficial to those with the aforementioned ineligible factors.

Abiraterone acetate in metastatic castration-resistant prostate cancer - the unanticipated real-world clinical experience.

BACKGROUND: There is much interest in confirming whether the efficacy of abiraterone acetate (AA) demonstrated within the trial setting is reproducible in routine clinical practice. We report the clinical outcome of metastatic castration-resistant prostate cancer (mCRPC) patients treated with AA in real-life clinical practice. METHODS: The clinical records of mCRPC patients treated with AA from all 6 public oncology centers in Hong Kong between August 2011 and December 2014 were reviewed. The treatment efficacy and its determinants, and toxicities were determined. RESULTS: A total of 110 patients with mCRPC were treated with AA in the review period, of whom 58 were chemo-naive and 52 had received prior chemotherapy (post-chemo). The median follow-up time was 7.5/11.4 months for chemo-naive/post-chemo patients. 6.9/15.4 % of chemo-naive/post-chemo patients had visceral metastases. The median overall survival (OS) and progression-free survival (PFS) were 18.1/15.5 months and 6.7/6.4 months for chemo-naive/post-chemo patients, respectively. Among chemo-naive patients, those with visceral diseases had significantly inferior OS (2.8 vs 18.0 p = 0.0007) and PFS (2.8 vs 6.8 months, p = 0.0088) than those without. Pain control was comparable in both groups of patients. The most common grade 3 or above toxicities were hypertension (6.9/5.8 %) and hypokalemia (3.4/3.8 %) in chemo-naive/post-chemo patients. In multivariate analysis, the presence of prostate-specific antigen (PSA) response (≥50 % drop of PSA from baseline) within the first 3 months of therapy was associated with favorable OS and PFS in both chemo-naive and post-chemo group. CONCLUSIONS: In clinical practice outside the trial setting, OS after AA in our chemo-naive patient cohort (18.1 months) was considerably shorter than that reported in the COU-AA-302 trial (34.7 months), and the OS was particularly short in those with visceral metastases (2.8 months). Conversely, AA was efficacious in post-chemo patients. AA resulted in comparable pain control in both groups of patients. The presence of PSA response within the first 3 months of treatment was a significant determinant of survival.

Importance of cycles of chemotherapy and postdocetaxel novel therapies in metastatic castration-resistant prostate cancer.

PURPOSE: With the emergence of various novel therapies including new generation taxane and androgen-targeted therapies, the optimal sequence of systemic treatment in metastatic castration-resistant prostate cancer (mCRPC) patients remains to be defined. Our aim is to investigate the impact of duration of docetaxel-based chemotherapy and postdocetaxel treatment in mCRPC patients. METHODS: The medical data of 57 Chinese mCRPC patients who received docetaxel-based chemotherapy in two oncology centers between 2003 and 2012 were reviewed. The treatment efficacy and toxicity were determined. The potential determinants of efficacy were also determined. RESULTS: Fifty-seven patients (median age 66 years, range 51-82 years) were given docetaxel-based chemotherapy, of whom 48 (84.2%) received 3-weekly docetaxel (52.5-75 mg/m(2)) and nine (15.8%) received weekly docetaxel (35 mg/m(2)). Postdocetaxel treatments were received by 31 (57.4%) patients, including abiraterone in 13 patients and cabazitaxel in one patient. The median follow-up time was 14.3 months. The median overall survival (OS) and progression-free survival were 20.8 months and 5.8 months, respectively. In multivariate analysis, eight cycles or more of chemotherapy [hazard ratio (HR) = 0.151, P < 0.0358], use of postdocetaxel treatment (HR = 0.346, P = 0.0005), and hemoglobin level of <10 (HR = 5.224, P < 0.0001) were independent determinants of OS. Patients who had received abiraterone and cabazitaxel as postdocetaxel treatment had significantly longer OS compared with those who received other postdocetaxel treatments (including rechallenge of docetaxel) and those who did not receive any postdocetaxel treatment (35.3 months vs. 20.8 months vs. 15.3 months, P = 0.00057). CONCLUSIONS: The results suggest that maximizing exposure to docetaxel-based chemotherapy followed by novel therapies would have a favorable survival impact on mCRPC patients.

Effects of acupuncture and acupressure on cancer-related fatigue: a systematic review.

PURPOSE/OBJECTIVES: To critically examine the evidence for acupuncture and acupressure in the management of cancer-related fatigue (CRF) in adult patients with cancer. DATA SOURCES: 18 databases were searched for randomized, controlled trials published in English and Chinese through April 2014. DATA SYNTHESIS: Given the heterogeneity of data, meta-analysis was not conducted. A six-step thematic analysis method was used to synthesize the results. CONCLUSIONS: Although results are inconclusive, acupuncture and acupressure tend to be effective in relieving CRF, with the former producing a greater improvement. Future research is recommended to contribute further evidence. IMPLICATIONS FOR NURSING: Nurses should know about the relative effectiveness of acupuncture and acupressure in the management of CRF to educate and support their patients.

Fine structure of corpora allata of castes with different rates of juvenile hormone production in the termite Reticulitermes flavipes.

The aim of this work is to describe corpora allata (CA) of several castes of the termite Reticulitermes flavipes that have different rates of juvenile hormone (JH) synthesis, with respect to differences in fine structure, volume, and intensity of allatostatin immunoreactivity in their innervation. The castes chosen are workers and their potential derivatives, apterous secondary reproductives and pre-soldiers (the precursors of soldiers). These castes, at the stages chosen, produce JH at low, high and intermediate rates respectively. Hormone production is positively correlated with volume and negatively correlated with intensity of allatostatin immunoreactivity in axons within the glands. Characteristics of fine structure that correlate with increased activity are increase in abundance and width of mitochondria, decrease in ability to fix and visualize smooth endoplasmic reticulum. These features have previously been described for CA of cockroaches and other insects. Glycogen in the CA of all of the castes studied, especially the large amounts in highly active glands of physogastric apterous reproductive females, is the most striking difference between the CA cells of R. flavipes and previously described CA of cockroaches, in which glycogen is absent throughout the reproductive cycles. This suggests that glycogen is an important source of energy for hormone production by termite CA.

Evidence for a Phe-Gly-Leu-amide-like allatostatin in the beetle Tenebrio molitor.

The allatostatins (ASTs) with Phe-Gly-Leu-amide C-terminal sequence are multifunctional neuropeptides discovered as inhibitors of juvenile hormone (JH) synthesis by corpora allata (CA) of cockroaches. Although these ASTs inhibit JH synthesis only in cockroaches, crickets, termites and locusts, isolation of peptides or of cDNA/genomic DNA or analysis of genomes indicates their occurrence in many orders of insects with the exception of coleopterans. The gene for these ASTs has not been found in the genome of the red flour beetle Tribolium castaneum (Family Tenebrionidae). Yet, in view of widespread occurrence of these peptides in insects, crustaceans and nematodes, they would be expected to occur in beetles. This study provides evidence for the presence of FGLa-like ASTs in the tenebrionid beetle, Tenebrio molitor, and scarabid beetle, Popillia japonica. Extract of brain from both beetles inhibited JH synthesis by cockroach CA dose dependently and reversibly. 20 brain equivalents of T. molitor and P. japonica extracts inhibited JH synthesis 64+/-5 and 65+/-0.6% respectively. Antibody against cockroach allatostatin (Diploptera punctata AST-7) used in an enzyme-linked immunosorbent assay reacted with brain extract of these beetles. Antibody against D. punctata AST-5 localized FGLa-like ASTs in the brain and subesophageal ganglion of T. molitor and P. japonica. In addition, pretreatment of T. molitor brain extract with anti-D. punctata AST-5 reduced the inhibition of JH synthesis and pretreatment of anti-D. punctata AST-5 with D. punctata AST-5 diminished the immunoreactivity of the antibody. Thus we predict that FGLa-like allatostatins will be found in beetles.

Identification of Phe-Gly-Leu-amide type allatostatin-7 in Reticulitermes flavipes: its localization in tissues and relation to juvenile hormone synthesis.

The allatostatins (ASTs), with a Tyr/Phe-Xaa-Phe-Gly-Leu/Ile-amide C-terminus, are neuropeptides that occur in many orders of insects, but are known to inhibit juvenile hormone (JH) synthesis by corpora allata (CA) only in cockroaches, crickets, and termites. 5 AST peptides with similar sequences to those of 6 species of cockroaches have been isolated and sequenced from extract of brain tissue of the termite Reticulitermes flavipes. The amino acid sequence of a 6th peptide, R. flavipes AST-7, determined by LC-MS/MS following HPLC fractionation of brain extract, is S-P-S-S-G-N-Q-R-L-Y-G-F-G-L-NH(2). The 8 terminal amino acids are identical to AST-7 of the cockroach Diploptera punctata. R. flavipes and D. punctata AST-7s inhibited JH synthesis by CA of both species equally and their affinity for antibody against D. punctata AST-7 is similar. Immunoreactivity of termite tissue with this antibody indicates neuro- and myomodulatory activity of the peptide in addition to its demonstrated allatostatic function. The density of AST immunostaining in axons within the CA of R. flavipes and the rate of JH synthesis by similar glands were negatively correlated. This is evidence that when AST is abundant in the glands it is being released in vivo to limit JH production.

Primary tumor volume of nasopharyngeal carcinoma: prognostic significance for local control.

PURPOSE: To study the prognostic significance of primary tumor volume on local control of nasopharyngeal carcinoma. METHODS AND MATERIALS: Between 1998 and 2001, 308 consecutive patients with nasopharyngeal carcinoma treated with radical intent were staged with MRI. On the basis of the extent of tumor infiltration outlined by a diagnostic radiologist, the gross tumor volume of the primary and involved retropharyngeal nodes (GTV-P) was delineated by a radiation oncologist for three-dimensional conformal radiotherapy to the nasopharyngeal region using the Helax-TMS Planning System. All patients were treated with 2 Gy daily to a total dose of 70 Gy in 6-7 weeks. Additionally, chemotherapy was given to 128 patients (42%). RESULTS: The median GTV-P for the whole series was 22 cm(3) (range, 1.4-218 cm(3)). Although the GTV-P varied substantially within each T stage, the overall correlation between these two parameters was strongly significant (p <0.01), with the median GTV-P 2.7 cm(3) for T1, 13.2 cm(3) for T2, 28.1 cm(3) for T3, and 65.5 cm(3) for T4. With a median follow-up of 1.9 years (range, 0.1-3.9 years), the 3-year local failure-free rate was 87%. The 3-year local failure-free rate was 97% for patients with a GTV-P <15 cm(3) compared with 82% for those with a GTV-P > or =15 cm(3) (p <0.01). On multivariate analysis (with T stage as a covariate), GTV-P remained an independent prognostic factor for the local failure-free rate (hazard ratio, 1.01; 95% confidence interval, 1.00-1.02; p <0.01). CONCLUSION: Our data suggested that GTV-P is a strongly significant factor for predicting local control of nasopharyngeal carcinoma. The risk of local failure was estimated to increase by 1% for every 1 cm(3) increase in primary tumor volume.