Intratumoral injection of oncolytic virus (H101) in combination with concurrent chemoradiotherapy for locally advanced cervical cancer.

OBJECTIVES: To evaluate the efficacy of primary tumor bulk reduction and the safety of concurrent chemoradiotherapy in combination with H101, a type of oncolytic virus, for the treatment of locally advanced cervical cancer. METHODS: Patients diagnosed with stage IIB or III cervical cancer according to the International Federation of Gynecology and Obstetrics (FIGO 2009), with tumor length ≥6 cm, were enrolled at Zhejiang Cancer Hospital from July 2015 to April 2017. All patients received concurrent chemoradiotherapy in combination with intratumoral H101 injection before and during external beam radiotherapy. Outcomes included progression free survival, overall survival, tumor regression after external beam radiotherapy, and side effects. RESULTS: A total of 23 patients were included in the safety analysis and, of these, 20 were included in the efficacy analysis. Median follow-up time was 38 (range 10-58) months. The 3 year local, regional, and overall progression free survival rates for the 20 patients were 95%, 95%, and 65%, respectively, and the 3 year overall survival rate was 74.3%. Median tumor length was reduced from 6.6 cm (range 6-7.3) before treatment to 4.1 cm (range 2.2-5.5) after external beam radiotherapy. Median tumor volume was reduced from 88.4 cm3 (range 41.2-126) before treatment to 20.8 cm3 (range 11.1-47.4) after external beam radiotherapy. Median percentage reduction of tumor length and volume were 37.7% and 75.1%, respectively. The major adverse event related to H101 was fever (91.3%). CONCLUSION: H101 injection may enhance primary tumor regression for locally advanced cervical cancer, with an acceptable safety profile. This treatment regimen should undergo further prospective randomized controlled studies.ChiCTR-OPC-15006142.

Surgery followed by concurrent radiochemotherapy as treatment for patients with locally recurrent cervical cancer.

BACKGROUND: No standard treatment exists for patients with recurrent cervical cancer. This study aimed to determine the role of surgery, followed by concurrent radiochemotherapy, as a treatment for recurrent pelvic cervical cancer without previous radiotherapy. METHODS: The current study identified patients diagnosed with vaginal and/or pelvic sidewall recurrent cervical cancer after primary surgery without radiotherapy in Zhejiang Cancer Hospital from May 2012 to November 2016. These enrolled patients underwent surgery, followed by concurrent radiochemotherapy and data were analyzed. RESULTS: This study enrolled 27 patients, including 11 with central (vaginal) and 16 with noncentral (pelvic sidewall with or without vaginal) recurrences. The median follow-up time after recurrence was 64 months (range, 5-110 months). All patients underwent surgery to resect the tumor as completely as possible and pelvic external beam radiotherapy (EBRT) with a median equivalent dose in 2 Gy fractions (EQD2) of 45.1 Gy (range, 44.3-47.8 Gy) with concurrent weekly cisplatin chemotherapy. The median EQD2 dose for the tumor bed/residual tumor was 51 Gy (range, 44.3-73.4 Gy), including 18 patients with a boost dose by EBRT or vaginal brachytherapy (VBT). The 5-year overall survival (OS) rates were 77.1% (central) and 65.7% (noncentral) without a statistically significant difference (P=0.246). Progression-free survival (PFS) rates were 81.8% (central) and 34.4% (noncentral), respectively, with a statistically significant difference (P=0.047). Three patients with noncentral recurrence experienced grade ≥3 complications associated with surgery. CONCLUSIONS: Surgery followed by concurrent radiochemotherapy was a feasible and effective treatment with acceptable complications for locally recurrent cervical cancer, which markedly improved the survival of pelvic sidewall recurrence.

The incidence and risk factors of acute radiation-induced dermatitis in gynecologic malignancies treated with intensity-modulated radiation therapy.

BACKGROUND: This study aimed to investigate the incidence of and potential risk factors for acute radiation-induced dermatitis (RID) in patients with gynaecological malignancies who underwent intensity-modulated radiation therapy (IMRT). METHODS: Ninety-six patients, who were diagnosed with gynaecological malignancies and underwent IMRT in the lower vagina and/or groin at Zhejiang Cancer Hospital (Hangzhou, Zhejiang, China) between January 2012 and June 2014, were enrolled. Clinical data were retrospectively collected. Acute RID grade ≥2 severity was defined as clinically relevant acute RID and sub-grouped accordingly. Univariate and multivariate analyses were performed. RESULTS: The incidence of grades 0, 1, 2, 3, and 4 acute RID was 2.1%, 43.8%, 35.4%, 18.8%, and 0%, respectively. Univariate analysis revealed that clinically relevant acute RID was independently correlated with hyperglycaemia (defined as venous fasting blood glucose level ≥7.1 mmol/L for 2 consecutive measurements), concurrent chemotherapy, and prophylactic use of triethanolamine emulsion (P<0.05). Patient age (P=0.521), body mass index (BMI) (P=0.893), and radiation boost (P=0.870) were not statistically significant factors. All variables with P<0.1 were included in the multivariate analysis together with radiation boost. Similarly, clinically relevant acute RID was independently correlated with hyperglycaemia [odds ratio (OR) 3.150; 95% confidence interval (CI), 1.019-9.736; P=0.046], synchronous chemotherapy (OR 3.515; 95% CI, 1.362-9.072; P=0.009), and prophylactic use of triethanolamine emulsion (OR 0.412; 95% CI, 0.170-0.998; P=0.049). CONCLUSIONS: Hyperglycaemia and synchronous chemotherapy were independent predictive factors for clinically relevant acute RID. Prophylactic use of triethanolamine emulsion may help to reduce the incidence of clinically relevant acute RID.

Autologous neu DNA vaccine can be as effective as xenogenic neu DNA vaccine by altering administration route.

We examined the therapeutic efficacy of xenogenic human N'-terminal neu DNA vaccine and autologous mouse N'-terminal neu DNA vaccine on MBT-2 tumor cells in C3H mice. Intramuscular injection of xenogenic and autologous neu DNA vaccines produced comparable therapeutic efficacies. Mouse and human N'-neu DNA vaccine induced tumor infiltration of CD8(+) T cells, while the human vaccine was less effective at stimulating natural killer cells. Depletion of CD8(+) T cells abolished the therapeutic efficacy of both types of DNA vaccines. On the other hand, xenogenic neu DNA vaccine showed significantly better therapeutic efficacy than autologous DNA vaccine with gene gun immunization. Increased infiltration of CD8(+) T cells was correlated with enhanced therapeutic efficacy in the human N'-neu group of mice. Therefore, intramuscular injection can enhance the therapeutic efficacy of autologous neu DNA vaccine.