Efficacy, toxicities, and prognostic factors of stereotactic body radiotherapy for unresectable liver metastases.

INTRODUCTION: This study aims to determine the outcomes of stereotactic body radiotherapy (SBRT) for liver metastases in patients not eligible for surgery. METHODS: This study included 31 consecutive patients with unresectable liver metastases who received SBRT between January 2012 and December 2017; 22 patients had primary colorectal cancer and nine patients had primary non-colorectal cancer. Treatments ranged from 24 Gy to 48 Gy in 3 to 6 fractions over 1 to 2 weeks. Survival, response rates, toxicities, clinical characteristics, and dosimetric parameters were evaluated. Multivariate analysis was performed to identify significant prognostic factors for survival. RESULTS: Among these 31 patients, 65% had received at least one prior regimen of systemic therapy for metastatic disease, whereas 29% had received chemotherapy for disease progression or immediately after SBRT. The median follow-up interval was 18.9 months; actuarial in-field local control rates at 1, 2, and 3 years after SBRT were 94%, 55%, and 42%, respectively. The median survival duration was 32.9 months; 1-year, 2-year, and 3-year actuarial survival rates were 89.6%, 57.1%, and 46.2%, respectively. The median time to progression was 10.9 months. Stereotactic body radiotherapy was well-tolerated, with grade 1 toxicities of fatigue (19%) and nausea (10%). Patients who received post-SBRT chemotherapy had significant longer overall survival (P=0.039 for all patients and P=0.001 for patients with primary colorectal cancer). CONCLUSION: Stereotactic body radiotherapy can be safely administered to patients with unresectable liver metastases, and it may delay the need for chemotherapy. This treatment should be considered for selected patients with unresectable liver metastases.

Sensorineural Hearing Loss in Nasopharyngeal Carcinoma Survivors in the Modern Treatment Era - The Early and Late Effects of Radiation and Cisplatin.

AIMS: Hearing loss is a common debilitating complication in nasopharyngeal carcinoma (NPC) survivors. The aim of the present study was to investigate the impact of inner ear/cochlear radiation dose and cisplatin use on early and late sensorineural hearing loss (SNHL) in NPC patients treated with radiotherapy alone, concurrent chemoradiation (cCRT) and induction chemotherapy followed by cCRT (iCRT) in the intensity-modulated radiotherapy era. MATERIALS AND METHODS: The study included 81 NPC patients treated with intensity-modulated radiotherapy between 2014 and 2016. Pure tone audiometry was carried out at baseline and follow-up. The effects of cochlear/inner ear radiation and cisplatin doses on early (<12 months) and late (≥24 months) SNHL were analysed using multivariable regression after adjusting for important predictors. RESULTS: In total, 156 ears were examined. In early SNHL (n = 136), cisplatin use predicted the incidence of early high-frequency SHNL (HF-SNHL) (odds ratio 6.4, 95% confidence interval 1.7-23.9, P = 0.005). Ninety ears were analysed for late SNHL (median follow-up 38 months). Inner ear/cochlear radiation and cisplatin doses and better pre-treatment hearing were independent predictors of threshold change at 4 kHz. Every 10 Gy increase in inner ear/cochlear Dmean resulted in 5-dB and 6-dB threshold changes, respectively (cochlear Dmean: B = 0.005, 95% confidence interval 0.0004-0.009, P = 0.031; inner ear Dmean: B = 0.006, 95% confidence interval 0.001-0.010, P = 0.014). Cisplatin use was associated with late HF-SNHL (odds ratio 3.74, 95% confidence interval 1.1-12.3, P = 0.031). In the cCRT and iCRT subgroups, no cisplatin dose-dependent ototoxicity was observed. Severe (≥30 dB) late HF-SNHL occurred in 14% and 25% of the patients when the cochlear dose constraints were 40 Gy and 44 Gy, respectively. The radiotherapy-alone group did not develop severe late HF-SNHL. CONCLUSION: Cochlear/inner ear radiation dose and cisplatin use showed differential and independent ototoxicity in early and late SNHL. As cochlear/inner ear dose-dependent ototoxicity was demonstrated, the cochlear dose constraint should be as low as reasonably achievable, especially when cisplatin is also administered.

A pre-optimised dosimetry system using a rigid applicator for intracavitary treatment of cervical carcinoma.

AIMS: Tumour control and complication risk have been major concerns in the treatment of cervical carcinoma. A review of dose distribution for intracavitary treatment of cervical carcinoma revealed that modification of the Manchester dosimetry system is necessary for cases of narrow-sized vagina. A revised dosimetry system was introduced in the present study, with the objective of optimising the dose coverage for the parametrium while minimising the bladder and rectum dosage by restricting the rectal dose so as not to exceed 75% of the brachytherapy prescription dose. MATERIALS AND METHODS: A suitable-sized applicator was selected according to the patient's anatomy. The revised system is optimised based on the fixed geometry of the applicator. The system was therefore predefined and the distribution of the treatment dose already determined before application. The revised system was applied to 135 cases, involving 540 applications. The clinical outcome in terms of local tumour control and complication rates is reported. The differences between the revised system and the Manchester system in terms of dose coverage for the parametrium and the rectum dose were compared. RESULTS: The results showed that higher rectal and parametrial dosages were obtained with the Manchester system as compared with the revised system. Our study showed that over 50% of our patients would have received a rectal dose close to 100% of the point A dose if the Manchester system was applied, whereas it was restricted to below 75% using the revised system. Using the revised system, the significance of the parametrial dosage coverage in relation to local control was assessed: the mean dose to the rectum and the bladder as a percentage of point A was 65.7 +/- 5% (range 50-85%) and 66.4 +/- 14% (range 29-116%), respectively. The 5-year actuarial local failure-free survival rates were 90, 92.9, 86.8, 100, 69.7 and 0% for stages IB, IIA, IIB, IIIA, IIIB and IV (P < 0.0001), respectively. The 3-year actuarial complication rates (grade 3/4) for proctitis and cystitis were 1.4 and 0.5%, respectively. The dosage coverage for the parametrium was found to be significant (P = 0.029) in relation to local control for early-stage disease. CONCLUSIONS: The favourable local tumour control and low complication rates shown by our results indicate that the revised system presents an optimal dose distribution, particularly for the application of small ovoids, whereas morbidity was reduced to a lower level without compromising local control.

Treatment results of endometrial carcinoma with positive peritoneal washing, adnexal involvement and serosal involvement.

AIMS: To review the treatment results of patients with endometrial carcinoma having positive peritoneal washing (PPW), adnexal involvement, uterine serosal involvement, or all three. MATERIALS AND METHODS: The treatment records of patients who had undergone primary surgery for endometrial cancer without distant metastasis during 1990--2001 at the Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong, were reviewed. Thirty-five patients were found to have involvement of positive PPW, adnexal involvement, uterine serosal involvement, or all three. Seven (20%) of them had gross or microscopic lymph-node metastasis. Thirty-three (94.3%) patients received adjuvant radiotherapy (28 whole-pelvic irradiation [WPI]; five abdominal radiotherapy [WART]). Two patients with solitary ovarian metastasis received chemotherapy, and one with isolated PPW also received adjuvant hormonal therapy. The median follow-up was 50.4 months (range 2.4-151.2 months). Multivariate analysis was carried out using the Cox regression proportional hazards model. RESULTS: Among the 28 patients with clinical or pathological node-negative disease (International Federation of Gynecology and Obstetrics [FIGO] stage IIIA), only two patients with solitary ovarian metastases developed recurrence. The 5-year actuarial disease-free survival (DFS) rates for the whole group and patients without lymph-node involvement were 77.9% and 91.7%, respectively. Five out of the seven patients with lymph-node involvement developed recurrences. Univariate analysis showed that lymph-node involvement (P < 0.0001) and high-grade disease (P = 0.011) were the significant poor prognostic factors. Multivariate analysis showed that lymph-node involvement was the only significant poor prognostic factor to predict poor 5-year DFS (P = 0.0001). Only one patient (3.7%) who had received WART developed grade 4 toxicity. CONCLUSIONS: This study showed that good treatment results could be obtained from patients with stage IIIA endometrial carcinoma without clinical or pathological lymph-node involvement after adjuvant radiotherapy, with acceptable late side-effects. The relative prognostic importance of individual IIIA involvement and the optimal adjuvant treatment remain to be determined.