Tumor Regression Rate Research Articles

Neoadjuvant treatment of adenocarcinoma of the rectum: Historical analysis and correlation between pathological regression rate and the outcomes.

e15177 Background: Treatment of locally advanced rectal cancer is based on chemoradiation associated with surgery. This treatment has high potential for curability. Tumor regression grade appears to be a prognostic factor and be influenced by the timing of surgery. Methods: A retrospective database was formed. We included patients submitted to neoadjuvant chemoradiotherapy and rectal surgery, treated at the Hospital de Clínicas, Porto Alegre. We analyzed outcomes, pathologic and treatment toxicity data. TRG was mensurated by the modified Ryan method, as the AJCC. We sought to analyze the better timing for surgery after chemotherapy, comparing the weeks after surgery with the rate of pCR. Statistical analysis was done with Kaplan Meier, Pearson's Chi-square and the Cox regression method. Results: We accrued 156 patients between 2006 and 2018. The rate of PFS at 3 and 5 years were 75% and 70%, respectively. The 5-year overall survival was 91%. The rate of pCR was 12.8%. TRG was an important prognostic factor. The absence of a pathological response (TRG 3) was associated with an increase in mortality, HR 3,148 (95% CI 1.6-12.2 P 0.003) and a decrease in PFS, HR 3,148 (95% CI 1, 7-5.8 P 0.0001). The 5-years PFS with TRG 0,1, 2 and 3 were 95%, 87%, 73.3% and 48%, respectively. Comparing the time between neoadjuvant treatment and surgery of less than 8 weeks versus 8 and 12 weeks versus above 12 weeks, the rates of pCR were 4.3%, 18.6% and 7.1% and the rates of TRG 3 were 32,6%, 18,6% and 57,1% (P 0.016). The chemotherapy regimens included 5FU bolus (75.1%) and capecitabine (19.1%). Doses of radiotherapy above 45 Gy were received by 80.5% of patients. Adjuvant treatment was not performed in 30.6% and 16.6% of these cases had positive pathological lymph nodes. The grade 3/4 adverse event rate was 21.6%. Conclusions: The outcomes found are favorable. The pathological tumor regression grade is an important prognostic factor. New strategies such as total neoadjuvant may play a role considering the rate of patients who cannot perform adjuvant chemotherapy. The time after neoadjuvant treatment seems to influence the tumor regression rate, especially between 8 and 12 weeks.

Preliminary study of S-1 maintenance therapy in extensive stage small-cell lung cancer.

e20080 Background: 4-6 cycles platinum and etoposide (EP) or platinum and irinotecan (IP) chemotherapy is the mainstay treatment for the extensive-stage small-cell lung cancer (SCLC); but the role of maintenance treatment is not fully understood. This study compared the efficacy and toxicities of 4-6 cycles EP or IP chemotherapy treatment followed by S-1 maintenance treatment or placebo control. Methods: In this phase 2, open-label, three-center preliminary study, patients who reached complete response (CR), partial response (PR) or stable disease (SD) after 4-6 cycles of EP or IP therapy were randomly assigned (1:1) with a minimization procedure. One group received oral S-1 25mg/mg2 twice a day as maintenance treatment until disease progression or unacceptable toxic effects. The other group was received placebo and routine follow-up. The primary end point of this study was progression-free survival (PFS) and the secondary end points were response rates, toxicities and overall survival (OS). This trial was registered with ClinicalTrials.gov, number NCT03769935. Results: A total of 89 patients were enrolled, of whom 45 received S-1 maintenance therapy and 44 received placebo. The median PFS was 6.35 months in the S-1 group, as compared with 5.98 months in the placebo group (hazard ratio for progression in the S-1 group, 1.057; 95% confidence interval [CI], 0.656-1.707; P = 0.820). The median OS was 10.82 months in the S-1 group, as compared with 10.09 months in the placebo group (hazard ratio for death in the S-1 group, 0.860; 95% CI, 0.374-1.617; P = 0.905). Tumor regression rate influenced patients’ survival. The PFS was 7.2 months and 5.3 months (p = 0.015), and OS was 12.9 months and 10.9 months (p = 0.042) in patients with CR or PR compared to in patients with SD after induction chemotherapy respectively. The adverse events were mild to moderate skin rash and acne, diarrhea, alopecia, dry skin and fatigue; which were mainly induced by induction chemotherapy and S-1 administration. Conclusions: S-1 maintenance treatment for extensive-stage SCLC had acceptable toxicities; however, there was no significant difference in PFS or OS statistically. Further research with novel agents in the maintenance setting is warranted. Clinical trial information: NCT03769935.

503P - Prognostic factors of chemo-radiotherapy efficacy in patients with locally-advanced rectal cancer

Background: We decided to evaluate preoperative clinical factors associated with progression free survival, overall survival and tumor regression in patients with locally-advanced rectal cancer after chemo-radiotherapy. Methods: we analyzed prospective database of patients with locally-advancded rectal cancer (cT3-4N0-2M0) who received preoperative chemo-radiotherapy followed by surgery in our center from 2004 to 2013. Multivariate regression analyses was performed to evaluate odds of absent morphological response (Dworak tumo regression rate system 0-2) and hazards of progression and deaths. Statistical analyses was performed with SPSS v.20. Results: Chemo-radiotherapy followed by surgery was performed in 457 patients with locally-advanced rectal cancer. The median f.-up was 46 months (2-141), 3-year progression free survival and overall survival were 79% and 91%, respectively. Multivariate regression analyses revealed factors associated with tumor regression rate 0-2 as high level (above normal range) CEA (carcinoembryonic antigen) before chemo-radiotherapy (OR 1.49 95%CI 1.11-2.02, p = 0.008), neutrophils count ≥ 7,000/µl (OR 2.29, 95%CI 1.0-5.2, p=0.05) and cT4 (OR 3.73, 95%CI 2.03-6.86, p < 0.001). Independent negative prognostic factors for progression free survival were perineural invasion (HR 3.1, 95% CI 1.43-6.89, p<0,001), neutrophil/lymphocyte ratio before surgery ≥ 3 (HR 1.8, 95%CI 1.37-2.42, p=0.01) and ypT3-4 or/and N + (HR 1.82, 95%CI 0.45-0.92, p<0.01). For overall survival: ypT3-4 or/and N + (HR 1.9, 95%CI 1.3-2.65, p<0.01), lymphatic vessel invasion (HR 2.4, 95%CI 1.27-4.59, p<0.01) and leucocytes count before surgery ≥11,000/µl (HR 3.1, 95%CI 1.33-7.33, p<0.01). Conclusions: ypTNM after preoperative chemo-radiotherapy more effective than cTNM predicts progression free and overall survival in patients with localy-advanced rectal cancer. Legal entity responsible for the study: Mikhail Fedyanin. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Stereotactic radiosurgery for hypervascular intracranial tumors.

To evaluate the safety and efficacy of SRS treatment of central neurocytomas (CNCs), cavernous sinus hemangiomas (CSHs), and glomus tumors (GTs); and to compare upfront stereotactic radiosurgery (SRS) and adjuvant SRS in the treatment of these hypervascular tumors. This was a retrospective review of consecutive CNCs, CSHs, and GTs treated with SRS between 1993 and 2017. Tumor response was categorized based on volumetric analysis on magnetic resonance imaging: (1) tumor regression [> 10% decrease in tumor volume (TV)]; (2) stable tumor (≤ 10% change in TV); or (3) tumor progression (> 10% increase in TV). Sixty hypervascular tumors (CNC: 28; CSH: 16; GT: 16) underwent SRS between 1993 and 2017. Margin doses were 13Gy, 12Gy, and 14Gy for CNCs, CSHs, and GTs, respectively. Tumor regression was observed in 54 tumors (90%) with initial SRS after a median follow-up of 82months. Relative reductions in TVs for CNCs were 38%, 52%, and 73% at 12, 24, and 48months, respectively. Relative reductions in TVs for CSHs were 51%, 68%, and 88% at 12, 24, and 48months, respectively. Relative reductions in TVs for GTs were 22%, 31%, and 47% at 12, 24, and 48months, respectively. Upfront SRS was performed in 26 patients (43%). No difference in relative TV reductions were found between upfront and adjuvant SRS. Adverse radiation effects were observed in five patients. No mortality was encountered. SRS for hypervascular tumors is associated with high rates of tumor regression with low risk of complications. No significant difference in rates of relative TV reduction were found between upfront and adjuvant SRS. Hence, upfront SRS may be considered in select patients.

Abstract B092: Myokine signaling blockade prevents androgen deprivation therapy-induced sarcopenia and promotes prostate tumor regression

Abstract One of the most significant side effects of androgen-deprivation therapy (ADT), the first-line therapy for recurrent and metastatic prostate cancer (PrCa), is sarcopenia (loss of skeletal muscle mass and function). ADT produces a significant disability syndrome in PrCa patients known as obese frailty. Use of ADT has been increasing such that side effects increasingly impact patient quality of life, and result in nursing home placement. The sarcopenia and functional loss of strength is recapitulated following castration of “middle-aged,” but not younger, male mice. In this model all five muscle-regulating TGFß superfamily members, known as myokines, are upregulated in distinctive temporal patterns during sarcopenia development. Complete myokine blockade fully restores muscle mass and strength in castrated mice. We castrated 6- to 9-month-old PbCre4 x PTENfl/fl PrCa-bearing mice and measured tumor volume (by high-frequency ultrasound), body composition (by NMR), muscle mass, fat mass, grip strength, and expression of TGFß family members. Tumor-bearing mice were treated with ActRIIB-Fc (or vehicle) to block myokine signaling; additional tumor-bearing mice were sacrificed biweekly to monitor myokine levels. In an autochthonous mouse model of PrCa, castration-induced changes closely resemble the loss of skeletal muscle strength and body composition that occurs in ADT treated patients. The reduction in muscle strength is comparable to that seen in patients. ADT reduces the mass of individual skeletal muscles, overall LBM, and grip strength. We examined the expression of myokines following castration and found that muscle levels of free dimeric myostatin, the activins, and GDF11 all increase over time, but with distinctive kinetics. Functionally, ActIIRB-Fc, which binds and blocks myokines, inhibits sarcopenia in our model, indicating that the myokines mediate ADT-induced sarcopenia. Surprisingly, this myokine inhibition also induced prostate tumor regression in the absence of ADT, suggesting a protumorigenic effect of myokines. Myokine inhibition also increased the rate of castration-induced prostate tumor regression in this model. In the tumor tissue and in the circulation, as in the muscle tissue of these mice, some of the myokines also increase post-castration. Myokines mediate the induction of sarcopenia following castration, and may also mediate tumor growth. These results suggest that myokines might be both biomarkers and potential targets for therapy to reduce this comorbidity in PrCa patients and may also control tumor growth directly. Citation Format: Chunliu Pan, Yanni Zulia, Kent L. Nasituk. Myokine signaling blockade prevents androgen deprivation therapy-induced sarcopenia and promotes prostate tumor regression [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B092.

Complete Local and Abscopal Responses from a Combination of Radiation and Nivolumab in Refractory Hodgkin's Lymphoma.

Until recently, patients with relapsed Hodgkin's lymphoma after brentuximab vedotin (Bv) treatments had poor treatment outcomes. Checkpoint inhibitors such as nivolumab and pembrolizumab that bind to and inhibit programmed cell death protein-1 (PD-1), have demonstrated an overall response rate of 70% in Hodgkin's lymphoma patients; however, complete response is still low at 20% with median progression-free survival of 14 months. There are ongoing clinical studies to seek out synergistic combinations, with the goal of improving the complete response rates for the cure of Hodgkin's lymphoma. Although radiotherapy has a limited survival benefit in such refractory patients, several preclinical models and anecdotal clinical evidence have suggested that combining local tumor irradiation with checkpoint inhibitors can produce systemic regression of distant tumors, an abscopal effect. Most of these reported studies on the response with local conformal radiotherapy and checkpoint inhibitors in combination with the anti-cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) antibody-ipilimumab are in melanoma. Here we report in our case series that the checkpoint inhibitors that block CTLA4 and B7-homolog 1 (B7-H1) or PD-1 in preclinical radiotherapy models have shown an increased the rate of tumor regression. Our case series demonstrates that combining local irradiation with anti-PD-1 checkpoint blockade treatment is feasible and synergistic in refractory Hodgkin's lymphoma. Correlative studies also suggest that the expression of programmed death-ligand 1 (PD-L1), DNA damage response and mutational tumor burden can be used as potential biomarkers for treatment response.

Tumor regression and growth rates of advanced prostate cancer in African American patients treated with docetaxel and prednisone.

e17049Background: Tumor growth rates and regression rates in patients with advanced prostate cancer have been shown to correlate with efficacy of treatment. However, few studies have compared the e...

Tumor growth and regression rate constants from the CLARINET study as surrogate endpoints for progression free survival: A novel assessment approach in cancer therapy.

e24329Background: Tumor size following cancer-related therapy is the result of regression of the treatment-sensitive fraction and growth of the treatment-resistant fraction, occurring simultaneousl...

Diffusion-weighted imaging in evaluating the efficacy of concurrent chemoradiotherapy in the treatment of non-small cell lung cancer.

To explore the predictive value of diffusion-weighted imaging (DWI) in evaluating the short-term efficacy of concurrent chemoradiotherapy (CCRT) in the treatment of patients with non-small cell lung cancer (NSCLC). A total of 192 patients with NSCLC were selected and treated with CCRT. Dynamic contrast-enhanced magnetic resonance imaging combined with DWI was performed on all patients before and after CCRT treatment. Correspondingly, apparent diffusion coefficient (ADC) values were recorded before treatment (ADCpre), during treatment (ADCmid), and after treatment (ADCpost). Tumor response was evaluated as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic power of quantitative DWI parameters in predicting the short-term efficacy of CCRT for patients with NSCLC. There were 21 patients with CR, 82 with PR, 77 with SD, and 12 with PD. The ADCpre was negatively correlated with tumor regression rate, whereas ADCmid, ADCpost, and their respective change rates ∆ADCmid and ∆ADCpost were positively related to tumor regression rate. The ROC curve analysis suggested ADCpre = 1.38 × 10-3 mm2/s, ∆ADCmid = 14.14%, and ∆ADCpost = 20.39% as thresholds to predict the short-term efficacy of CCRT, with corresponding areas under the curve of 0.637, 0.743, and 0.752, respectively. These findings indicate that DWI provides promising predictive value in evaluating the short-term efficacy of CCRT in the treatment of patients with NSCLC.

Early ultrasonographic tumor regression after linear accelerator stereotactic fractionated photon radiotherapy of choroidal melanoma as a predictor for metastatic spread

Background and purposeDuring extended follow-up (of up to 15 years), approximately fifty percent of patients with choroidal melanoma will develop metastatic disease and eventually die. Thus, continuing research on prognostic factors, early detection and treatment is necessary. Height regression rates both after plaque brachytherapy and proton beam irradiation have been shown to have prognostic value. The purpose of this study was to analyze the influence of early tumor regression rate after treatment of choroidal melanoma with LINAC stereotactic fractionated radiotherapy (SFRT) as an independent risk factor for metastasis. Material and methods256 patients with choroidal melanoma treated with LINAC SFRT were included. Follow-up included standardized echography yielding apical height, smallest and largest basal linear diameter, tumor volume and mean reflectivity. The influence of baseline measurements and of a longitudinal, normalized area under the curve coefficient (NAC) of the latter marker on metastasis risk was assessed. ResultsNAC for tumor thickness at months 3, 6, and 12 had a statistically significant (p < 0.001) non-linear effect on risk of metastasis. Additionally, ultrasonographic baseline tumor dimensions, but not internal reflectivity were found to be statistically significant risk factors for metastasis. ConclusionsOur results demonstrate a non-linear influence of regression rate of choroidal melanoma as independent risk factor of metastatic disease after LINAC SFRT. These prove the clinical experience that, in comparison to rather slow regressions, very quick and very slow early tumor responses to LINAC SFRT are associated with a significantly higher metastasis risk.

Value of introvoxel incoherent motion imaging on evaluating concurrent chemoradiotherapy response in patients with advanced uterine cervix cancer

Objective To investigate the value of introvoxel incoherent motion (IVIM) using 3.0 T MRI to evaluate response to concurrent chemoradiotherapy (CCRT) in patients with advanced uterine cervix cancer. Methods From July 2015 to December 2016, 63 patients with advanced (≥ⅡB) cervical cancer diagnosed by clinical and imaging study, who had completed CCRT plan in Henan Cancer Hospital, were prospectively enrolled. Pelvic MRI protocol including T1WI, T2WI, IVIM and dynamic contrasted enhanced scans were performed in each patient before CCRT and 3 weeks after starting therapy (total dose of 30 Gy), and at the end of therapy (total dose of 90 Gy, 8 weeks after therapy). The mean values of ADC, true molecular diffusion coefficient (D), pseudodiffusion coefficient (D*) and perfusion fraction (f) in each tumor at pre-therapy, in the middle of therapy and post-therapy were measured and recorded as ADC-pre, D-pre, D*-pre, f-pre;ADC-mid, D-mid, D*-mid, f-mid and ADC-post, D-post, D*-post, f-post, respectively;the change rates of these parameters during and after therapy (recorded as ΔADC-mid, ΔD-mid, ΔD*-mid, Δf-mid; ΔADC-post, ΔD-post, ΔD*-post, Δf-post) were also calculated. Patients were classified into response group and non-response group, according to response evaluation criteria in solid tumors after CCRT. MRI imaging study was performed in each patient within 1 month after CCRT to follow up, and tumor regression rate was calculated. The Mann-Whitney U test was used to compare differences of parameters and their change rates between response group and non-response group. Spearman correlation analysis was performed to assess relationships between parameters, parameter change rates and tumor regression rate. Logistic regression model was applied to find potential ADC values for predicting therapeutic response. ROC was used to analyze efficacy of ADC values for evaluating therapeutic response in advanced uterine cervix cancer after CCRT. Results The mean value of tumor maximum diameter before and after therapy was (47.5 ± 12.9) and (12.8 ± 10.0) mm, tumor regression rate was (66.7 ± 33.6)%. Forty-eight patients were in the response group and 15 in the non-response group. The mean value of ADC-pre, D-pre, D*-pre and f-pre was 0.74(0.43, 1.14)×10-3, 0.58(0.33, 0.91)×10-3, 12.12(2.30, 21.4)×10-3mm2/s, 9.65%(4.45%, 13.89%), respectively. Tumor regression rate had positive correlation with ADC-pre and D-pre (r=0.773, 0.840;P<0.05). Responders had increased ADC-pre, D-pre values than non-responders, which had statistically significant difference (P<0.05). Responders had increased ADC-mid, D-mid and f-mid values than non-responders, which had statistically significant difference (P<0.05), tumor regression rate had positive correlation with ADC-mid, D-mid and f-mid (r=0.808, 0.834, 0.563;P<0.05). Responders had increased ADC-post, D-post and f-post values than non-responders, which had statistically significant difference (P<0.05), tumor regression rate had positive correlation with ADC-post and D-post (r=0.799, 0.829;P<0.05).Tumor regression rate had positive correlation with ΔADC-mid, ΔD-mid, Δf-mid(r=0.526, 0.573, 0.454;P<0.05) and with ΔADC-post, ΔD-post, Δf-post (r=0.541, 0.555, 0.388;P<0.05). Responders had increased ΔADC-mid, ΔD-mid, Δf-mid and ΔADC-post, ΔD-post, Δf-post, which had statistically significant difference (P<0.05). Logistic regression analysis revealed only ADC-pre and D-post could be independent factors to predict therapeutic response in advanced uterine cervix cancer after CCRT, values of B, Wald, odds ratio and P was 22.488, 8.431, 1.429, 0.004 and 16.542, 8.517, 1.779, 0.004. ROC analysis showed the area under the curve (AUC) of ADC-pre, D-pre, ΔADC-mid, ΔD-mid, Δf-mid, ΔADC-post, ΔD-post and Δf-post for predicting therapeutic response in advanced uterine cervix cancer after CCRT were 0.890, 0.926, 0.942, 0.851, 0.803, 0.929, 0.951 and 0.906, respectively. Conclusion The IVIM parameters before and during CCRT process and their changes are valuable for predicting and evaluating therapeutic response in advanced uterine cervix cancer after CCRT, with high clinical practice value. Key words: Uterine cervical neoplasms; Magnetic resonance imaging; Introvoxel incoherent motion; Efficacy evaluation; Concurrent chemoradiotherapy

New frontiers in oncolytic viruses: optimizing and selecting for virus strains with improved efficacy.

Oncolytic viruses have demonstrated selective replication and killing of tumor cells. Different types of oncolytic viruses – adenoviruses, alphaviruses, herpes simplex viruses, Newcastle disease viruses, rhabdoviruses, Coxsackie viruses, and vaccinia viruses – have been applied as either naturally occurring or engineered vectors. Numerous studies in animal-tumor models have demonstrated substantial tumor regression and prolonged survival rates. Moreover, clinical trials have confirmed good safety profiles and therapeutic efficacy for oncolytic viruses. Most encouragingly, the first cancer gene-therapy drug – Gendicine, based on oncolytic adenovirus type 5 – was approved in China. Likewise, a second-generation oncolytic herpes simplex virus-based drug for the treatment of melanoma has been registered in the US and Europe as talimogene laherparepvec.

Predictive role of REG IV and YKL-40 in locally advanced rectal cancer patients receiving neoadjuvant chemoradiotherapy

Abstract Objective: Patients with locally advanced rectal cancer (LARC) need extensive surgical interference. Preoperative neoadjuvant chemoradiotherapy (CRT) shifts this extensive surgical procedure to another sphincter saving one as well as lowers patient's morbidity and mortality. Till now, there is no definite method to predict patients' response to neoadjuvant CRT. Methods: REG IV and YKL-40 immunohistochemistry was evaluated in pre-treatment endoscopic biopsies from 42 LARC cases who received neoadjuvant CRT followed by surgical interference. The findings were correlated with the clinico-pathological features, tumor response and tumor regression grade of the post-operative specimens. Results: REG IV high expression was associated with advanced post-treatment pathological tumor status, post -treatment pathological nodal status and presence of lympho-vascular invasion with statistical significance. Furthermore, it was correlated with a lower extent of tumor regression after neoadjuvant CRT. All patients with pCR exhibited negative/low REG IV expression and only 13.6% of the responders showed high REG IV expression with statistical significance. YKL-40 immunohistochemical expression was highly associated with the tumor regression rate where 85% of LARC patients with poor neoadjuvant CRT response highly expressed YKL-40 and 66.6% of patients with complete regression showed negative\low expression of YKL-40. Conclusion: Our findings implicate REG IV and YKL-40 as important predictors of neoadjuvant CRT response in locally advanced rectal cancer.

Moderate Heat Application Enhances the Efficacy of Nanosecond Pulse Stimulation for the Treatment of Squamous Cell Carcinoma

Nanosecond pulse stimulation as a tumor ablation therapy has been studied for the treatment of various carcinomas in animal models and has shown a significant survival benefit. In the current study, we found that moderate heating at 43°C for 2 minutes significantly enhanced in vitro nanosecond pulse stimulation-induced cell death of KLN205 murine squamous cell carcinoma cells by 2.43-fold at 600 V and by 2.32-fold at 900 V, as evidenced by propidium iodide uptake. Furthermore, the ablation zone in KLN205 cells placed in a 3-dimensional cell-culture model and pulsed at a voltage of 900 V at 43°C was 3 times larger than in cells exposed to nanosecond pulse stimulation at room temperature. Application of moderate heating alone did not cause cell death. A nanosecond pulse stimulation electrode with integrated controllable laser heating was developed to treat murine ectopic squamous cell carcinoma. With this innovative system, we were able to quickly heat and maintain the temperature of the target tumor at 43°C during nanosecond pulse stimulation. Nanosecond pulse stimulation with moderate heating was shown to significantly extend overall survival, delay tumor growth, and achieve a high rate of complete tumor regression. Moderate heating extended survival nearly 3-fold where median overall survival was 22 days for 9.8 kV without moderate heating and over 63 days for tumors pulsed with 600, 100 ns pulses at 5 Hz, at voltage of 9.8 kV with moderate heating. Median overall survival in the control groups was 24 and 31 days for mice with untreated tumors and tumors receiving moderate heat alone, respectively. Nearly 69% (11 of 16) of tumor-bearing mice treated with nanosecond pulse stimulation with moderate heating were tumor free at the completion of the study, whereas complete tumor regression was not observed in the control groups and in 9.8 kV without moderate heating. These results suggest moderate heating can reduce the necessary applied voltage for tumor ablation with nanosecond pulse stimulation.

Prospective matched study on comparison of volumetric-modulated arc therapy and intensity-modulated radiotherapy for nasopharyngeal carcinoma: dosimetry, delivery efficiency and outcomes.

Background: The purpose of this study is to assess the feasibility of volumetric-modulated arc therapy (VMAT) for nasopharyngeal carcinoma (NPC) patients by comparing the physical dosimetry, delivery efficiency and clinical outcomes with intensity-modulated radiotherapy (IMRT).Methods: A prospective matched study was performed for patients with newly diagnosed NPC who underwent VMAT or IMRT. The patients in two groups were equally matched in terms of gender, age, tumor stage and chemotherapy. The target coverage, homogeneity index (HI) and conformity index (CI) of the planning target volume (PTV), organs at risk (OARs) sparing, average treatment time and clinical outcomes were analyzed.Results: From June 2013 to August 2015, a total of 80 patients were enrolled in this study, with 40 patients in each group. The coverage of PTV was similar for both groups. D2 was observed slight difference only in early stage disease (T1-2) (VMAT vs. IMRT, 7494±109 cGy vs. 7564±92 cGy; p=0.06). The HI of VMAT group was better than that of IMRT group (p=0.001), whereas CI was slightly worse (p=0.061). The maximum doses received by the brain stem, spinal cord, and optic nerve of VMAT were higher than those of IMRT (p<0.05). But the irradiation volumes in healthy tissue were generally lower for VMAT group, with significant differences in V20, V25 and V45 (p<0.05). With regard to the delivery efficiency compared with IMRT (1160 ± 204s), a 69% reduction in treatment time was achieved by VMAT (363 ± 162s). Both groups had 5 cases of nasopharyngeal residual lesions after radiotherapy. The 2-year estimated local relapse-free survival, regional relapse-free survival and locoregional relapse-free survival, distant metastasis-free survival, disease-free survival and overall survival were similar between two groups, with the corresponding rates of 100%, 97.4%, 97.4%, 90.0%, 90.0% and 92.4% in VMAT group, and 100%, 100%, 100%, 95.0%, 95.0% and 97.5% in IMRT group, respectively.Conclusions: Both VMAT and IMRT can meet the clinical requirements for the treatment of NPC. The short-term tumor regression rates and 2-year survival rates with the two techniques are comparable. The faster treatment time benefits of VMAT will enable more patients to receive precision radiotherapy.

Application of Alphaviral Vectors for Immunomodulation in Cancer Therapy.

The lack of specific and efficient cancer therapies has influenced the development of novel approaches, such as immunotherapy, which from its original application of immunogenic protein delivery has developed into the use of more sophisticated recombinant gene delivery methods to achieve better safety and efficacy profiles. This approach involves viral and non-viral delivery systems. Expression vectors have been engineered for alphaviruses, including Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus. For immunotherapeutic applications, recombinant particles, RNA replicons and layered DNA vectors that express tumor-associated antigens (TAAs) and cytokines have been studied in animal models and in a few clinical trials. Immunization studies with TAAs and cytokines have elicited strong antibody responses and vaccination has provided protection against challenges with tumor cells in mouse models. Furthermore, the combination of TAAs and cytokines, antibodies and growth factors and the co-administration of chemotherapeutics and bacteriabased adjuvants have enhanced immunogenicity. Intratumoral and systemic delivery of recombinant alphavirus particles has demonstrated significant tumor regression and prolonged survival rates in rodent tumor models. Alphavirus-based immunotherapy represents a rapid and efficient method for prophylactic and therapeutic applications in animal models.

Predictors for the efficacy of Endostar combined with neoadjuvant chemotherapy for stage IIIA (N2) NSCLC.

Endostar (rh-endostatin) is a new recombinant human endostatin, which could inhibit cell proliferation, angiogenesis, and tumor growth. To explore anti-angiogenesis short-term efficacy combined with neoadjuvant chemotherapy for stage IIIA (N2) non-small cell lung cancer (NSCLC), and identify the potential predictive factors. We pathologically examined 26 patients diagnosed with stage IIIA (N2) NSCLC who received NP chemotherapy alone or combined with Endostar, respectively. Our results indicated that total clinical benefit rate (CBR) 87.5% and 64% (p= 0.76), respectively. The clinical benefit (CB) patients in the treatment group showed significant changes in endothelial progenitor cells (EPC), vascular endothelial growth factor (VEGF), blood flow (BF), permeability surface (PMS), and microvascular density (MVD) before and after treatment. Compared with CB patients in the control group, changes in EPC and MVD (only) before and after treatment were significant. The variation of EPC, PMS, and MVD before and after treatment in the treatment group showed positive correlation with tumor regression rate (TRR) and the variation of MVD, whereas those of EPC and PMS demonstrated positive correlations with variation of MVD before and after treatment. Our findings suggested that PMS and EPC may be used as a predictive factor for the short-term efficacy of the combined therapy in NSCLC.

The predictive value of pre- and post-induction chemotherapy plasma EBV DNA level and tumor volume for the radiosensitivity of locally advanced nasopharyngeal carcinoma.

This study was dedicated to investigate the predictive value of pre- and post-induction chemotherapy plasma EBV (Epstein-Barr Virus) DNA level and tumor volume for the radiosensitivity of locally advanced NPC. 129 previously untreated locally advanced NPC patients were enrolled. Plasma EBV-DNA copy number and tumor volume was detected before and after induction chemotherapy. The tumor volume was also measured after radiotherapy. Among 129 patients, 98 were positive for EBV DNA. The residual gross target volume of the primary tumor (GTVnx) and GTVnd after radiotherapy was positively correlated with post-induction chemotherapy EBV copy number (rho=0.357, P<0.001; rho=0.356, P<0.001, respectively). Univariate logistic regression analyses showed that the AUC of ROC curves of post-induction chemotherapy tumor volume, tumor regression rate before and after induction chemotherapy, post-induction EBV copy number, EBV decrease rate for predicting no residual nasopharyngeal tumor were 0.859, 0.782, 0.678 and 0.657, respectively. Multivariate logistic analyses showed that T stage, post-induction chemotherapy EBV copy number and tumor volume were independent predictors for no residual nasopharyngeal tumor after radiotherapy. The changes in plasma EBV DNA and tumor volume during treatment could be used to predict the sensitivity of locally advanced NPC patients in response to intensity-modulated radiation therapy (IMRT).

Correlation of quantitative parameters of magnetic resonance perfusion-weighted imaging with vascular endothelial growth factor, microvessel density and hypoxia-inducible factor-1α in nasopharyngeal carcinoma: Evaluation on radiosensitivity study.

To investigate the correlation of parameters of magnetic resonance perfusion-weighted imaging (MR-PWI) with the expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α) and microvessel density (MVD) in nasopharyngeal carcinoma (NPC) so as to explore the value of predicting radiosensitivity. A prospective study. Department of Head-and-neck radiotherapy in Hunan Cancer Hospital. Ninety-four patients of NPC were included between December 2013 and December 2014. The expression of VEGF, MVD and HIF-1α was studied by immunohistochemistry, and magnetic resonance perfusion-weighted imaging (MR-PWI) was performed before and after undergoing radiotherapy (20Gy dose). Parameters of MR-PWI, volume of primary tumour and rate of tumour remission were measured and calculated. Patients with primary local tumour were then divided into completely response group (CR group) and partially response group (non-CR group) according to tumour regression condition. Relevant parameters were analysed by Spearman, and diagnostic efficiency of radiosensitivity was analysed by receiver operating characteristic curve (ROC). The expression of VEGF was positively correlated with MVD (r=.322,P<.05), but the expression of HIF-1α was no significant correlations with VEGF and MVD. The expression VEGF was in positive correlation with fractional plasma volume (fpv) (r=.339, P=.05) before radiotherapy. There was a significant difference in the quantitative parameters of MR-PWI between CR group and non-CR group during the course of radiotherapy and at the end of radiotherapy treatment. The change of blood reflux constant (Δkep20) and extravascular extracellular space volume fraction (ΔVe20) before and after treatment was positively correlated with primary local tumour remission condition after 3month treatment; Δkep and ΔVe were negatively correlated with primary local tumour remission condition after 3months. Tumour regression rate was only positively correlated with Ve and the average volume of primary tumour after 2week treatment (V1). ROC curve showed that R20≥65.69%, and was considered as a threshold to predict primary local tumour remission, with a sensitivity of 0.84 and specificity of 0.69, and area under the curve was 0.819 (P=.000). The parameters of MR-PWI with the expression of VEGF, HIF-1α and MVD could be guidance for predicting radiosensitivity in NPC.

Primary and Nodal Tumor Regression Rates: Towards CT-Based 3D Volumetric Characterization of Response to Induction Chemotherapy in Oropharynx Cancer patients

Primary and Nodal Tumor Regression Rates: Towards CT-Based 3D Volumetric Characterization of Response to Induction Chemotherapy in Oropharynx Cancer patients