Locoregional Tumor Control Research Articles

Optimal surgical approach for esophageal cancer in the era of minimally invasive esophagectomy and neoadjuvant therapy

The optimal surgical technique for the potentially curative treatment of patients with esophageal cancer is still under debate. The transhiatal esophagectomy (THE) with limited lymphadenectomy mainly focuses on a decrease of postoperative morbidity and mortality by preventing a formal thoracotomy. The transthoracic esophagectomy (TTE) with extended two-field lymphadenectomy attempts to improve the radicality of the resection and thus to increase locoregional tumor control, but is associated with increased postoperative morbidity. The recent introduction of different minimally invasive techniques probably decreases postoperative morbidity following TTE, with reduction of especially pulmonary complications, but high-quality evidence is still limited. It is widely agreed that extended lymphadenectomy as performed during TTE provides the benefit of more accurate staging, but its effect on improvement of survival is still debated. The literature on this topic is contradictory and the choice of surgical approach is primarily driven by personal opinions and institutional preferences. Moreover, the available evidence is mainly based on patients who underwent surgery alone without neoadjuvant therapy. Results of recent studies suggest that neoadjuvant chemoradiotherapy abolishes any possibly positive effect of extended lymphadenectomy as performed during TTE on survival, but this effect should be confirmed in future research. This review gives an overview and reflects the authors' personal view on the role of TTE and THE in the treatment of potentially curative treatment of patients with locally advanced esophageal cancer in the era of minimally invasive esophagectomy and neoadjuvant treatment and outlines future research perspectives.

Concurrent chemoradiotherapy for T3-4 and N0-1 nasopharyngeal cancer: Asian multicenter trial of the Forum for Nuclear Cooperation in Asia.

The aim of this study was to evaluate the toxicity and efficacy of radiotherapy concurrent with weekly cisplatin for T3–4 and N0–1 nasopharyngeal cancer. Between 2005 and 2010, 70 patients with nasopharyngeal cancer (T3–4 N0–1 M0, World Health Organization Type 2–3) from Vietnam, Indonesia, Malaysia and Thailand were registered. Patients were treated with 2D radiotherapy concurrent with weekly cisplatin (30 mg/m2). Neither adjuvant nor induction chemotherapy was given. Ninety-three percent of the patients completed at least four cycles of weekly cisplatin during radiotherapy. The median total doses for the primary tumor and positive lymph nodes were 70 and 66 Gy, respectively. The median overall treatment time of concurrent chemoradiotherapy was 52 days. No treatment-related deaths occurred. Grade 3–4 acute toxicities of mucositis, nausea/vomiting and leukopenia were observed in 34%, 4% and 4% of patients, respectively. With a median follow-up time of 52 months for the 40 surviving patients, the 3-year local control, locoregional tumor control, distant metastasis–free survival and overall survival rates were 80%, 75%, 74% and 80%, respectively. In conclusion, the current results illustrate that our concurrent chemoradiotherapy regimen was feasible, but disease control remained insufficient. Further research is encouraged in order to improve clinical outcomes.

Post-operative renal function following nephrectomy as part of en bloc resection of retroperitoneal sarcoma (RPS).

Although resection of RPS with en bloc nephrectomy confers the potential benefit of improved locoregional tumor control, little has been published about the long-term post-operative renal function of these patients. Retrospective review of 54 patients undergoing nephrectomy for RPS was performed. Clinicopathologic and treatment characteristics, pre- and post-operative creatinine (Cr) values, and estimated glomerular filtration rates (eGFR) were recorded. The primary outcome measure was progression of chronic kidney disease (CKD) stage. Median preoperative eGFR was 85 ml/min. Post-nephrectomy, median nadir eGFR was 44 ml/min, rebounding to 62 ml/min at median follow-up of 50 months. Of 49 patients with preoperative eGFR ≥60 ml/min (CKD stage 1,2), 51% preserved eGFR ≥60 postoperatively, whereas 49% progressed to CKD stage 3 (eGFR 30-59). Independent risk factors for progression of CKD stage were age and preoperative eGFR. Eleven patients died of recurrent disease, whereas no patient died of end stage renal disease (ESRD) or required dialysis. Although progression of CKD stage occurs in nearly one-half of patients followed for more than 4 years after nephrectomy for RPS, no patient progressed to ESRD or had a limitation in systemic therapy options, even with progression to CKD stage 3.

Prognostic Value of Pretherapeutic Tumor-to-Blood Standardized Uptake Ratio in Patients with Esophageal Carcinoma.

Despite ongoing efforts to develop new treatment options, the prognosis for patients with inoperable esophageal carcinoma is still poor and the reliability of individual therapy outcome prediction based on clinical parameters is not convincing. The aim of this work was to investigate whether PET can provide independent prognostic information in such a patient group and whether the tumor-to-blood standardized uptake ratio (SUR) can improve the prognostic value of tracer uptake values. (18)F-FDG PET/CT was performed in 130 consecutive patients (mean age ± SD, 63 ± 11 y; 113 men, 17 women) with newly diagnosed esophageal cancer before definitive radiochemotherapy. In the PET images, the metabolically active tumor volume (MTV) of the primary tumor was delineated with an adaptive threshold method. The blood standardized uptake value (SUV) was determined by manually delineating the aorta in the low-dose CT. SUR values were computed as the ratio of tumor SUV and blood SUV. Uptake values were scan-time-corrected to 60 min after injection. Univariate Cox regression and Kaplan-Meier analysis with respect to overall survival (OS), distant metastases-free survival (DM), and locoregional tumor control (LRC) was performed. Additionally, a multivariate Cox regression including clinically relevant parameters was performed. In multivariate Cox regression with respect to OS, including T stage, N stage, and smoking state, MTV- and SUR-based parameters were significant prognostic factors for OS with similar effect size. Multivariate analysis with respect to DM revealed smoking state, MTV, and all SUR-based parameters as significant prognostic factors. The highest hazard ratios (HRs) were found for scan-time-corrected maximum SUR (HR = 3.9) and mean SUR (HR = 4.4). None of the PET parameters was associated with LRC. Univariate Cox regression with respect to LRC revealed a significant effect only for N stage greater than 0 (P = 0.048). PET provides independent prognostic information for OS and DM but not for LRC in patients with locally advanced esophageal carcinoma treated with definitive radiochemotherapy in addition to clinical parameters. Among the investigated uptake-based parameters, only SUR was an independent prognostic factor for OS and DM. These results suggest that the prognostic value of tracer uptake can be improved when characterized by SUR instead of SUV. Further investigations are required to confirm these preliminary results.

Normal tissue complication models for clinically relevant acute esophagitis (≥ grade 2) in patients treated with dose differentiated accelerated radiotherapy (DART-bid).

BackgroundOne of the primary dose-limiting toxicities during thoracic irradiation is acute esophagitis (AE). The aim of this study is to investigate dosimetric and clinical predictors for AE grade ≥ 2 in patients treated with accelerated radiotherapy for locally advanced non-small cell lung cancer (NSCLC).Patients and methods66 NSCLC patients were included in the present analysis: 4 stage II, 44 stage IIIA and 18 stage IIIB. All patients received induction chemotherapy followed by dose differentiated accelerated radiotherapy (DART-bid). Depending on size (mean of three perpendicular diameters) tumors were binned in four dose groups: <2.5 cm 73.8 Gy, 2.5–4.5 cm 79.2 Gy, 4.5–6 cm 84.6 Gy, >6 cm 90 Gy. Patients were treated in 3D target splitting technique. In order to estimate the normal tissue complication probability (NTCP), two Lyman models and the cutoff-logistic regression model were fitted to the data with AE ≥ grade 2 as statistical endpoint. Inter-model comparison was performed with the corrected Akaike information criterion (AICc), which calculates the model’s quality of fit (likelihood value) in relation to its complexity (i.e. number of variables in the model) corrected by the number of patients in the dataset. Toxicity was documented prospectively according to RTOG.ResultsThe median follow up was 686 days (range 84–2921 days), 23/66 patients (35 %) experienced AE ≥ grade 2. The actuarial local control rates were 72.6 % and 59.4 % at 2 and 3 years, regional control was 91 % at both time points. The Lyman-MED model (D50 = 32.8 Gy, m = 0.48) and the cutoff dose model (Dc = 38 Gy) provide the most efficient fit to the current dataset. On multivariate analysis V38 (volume of the esophagus that receives 38 Gy or above, 95 %-CI 28.2–57.3) was the most significant predictor of AE ≥ grade 2 (HR = 1.05, CI 1.01–1.09, p = 0.007).ConclusionFollowing high-dose accelerated radiotherapy the rate of AE ≥ grade 2 is slightly lower than reported for concomitant radio-chemotherapy with the additional benefit of markedly increased loco-regional tumor control. In the current patient cohort the most significant predictor of AE was found to be V38. A second clinically useful parameter in treatment planning may be MED (mean esophageal dose).Electronic supplementary materialThe online version of this article (doi:10.1186/s13014-015-0429-1) contains supplementary material, which is available to authorized users.

DEGRO practical guidelines for radiotherapy of breast cancer V: Therapy for locally advanced and inflammatory breast cancer, as well as local therapy in cases with synchronous distant metastases.

AimThe purpose of this work is to give practical guidelines for radiotherapy of locally advanced, inflammatory and metastatic breast cancer at first presentation.MethodsA comprehensive survey of the literature using the search phrases “locally advanced breast cancer”, “inflammatory breast cancer”, “breast cancer and synchronous metastases”, “de novo stage IV and breast cancer”, and “metastatic breast cancer” and “at first presentation” restricted to “clinical trials”, “randomized trials”, “meta-analysis”, “systematic review”, and “guideline” was performed and supplemented by using references of the respective publications. Based on the German interdisciplinary S3 guidelines, updated in 2012, this publication addresses indications, sequence to other therapies, target volumes, dose, and fractionation of radiotherapy.ResultsInternational and national guidelines are in agreement that locally advanced, at least if regarded primarily unresectable and inflammatory breast cancer should receive neoadjuvant systemic therapy first, followed by surgery and radiotherapy. If surgery is not amenable after systemic therapy, radiotherapy is the treatment of choice followed by surgery, if possible. Surgery and radiotherapy should be administered independent of response to neoadjuvant systemic treatment. In patients with a de novo diagnosis of breast cancer with synchronous distant metastases, surgery and radiotherapy result in considerably better locoregional tumor control. An improvement in survival has not been consistently proven, but may exist in subgroups of patients.ConclusionRadiotherapy is an important part in the treatment of locally advanced and inflammatory breast cancer that should be given to all patients regardless to the intensity and effect of neoadjuvant systemic treatment and the extent of surgery. Locoregional radiotherapy in patients with primarily distant metastatic disease should be prescribed on an individual basis.

Patterns of Recurrence and Survival after Surgery or Stereotactic Radiotherapy for Early Stage NSCLC

Surgery is the standard treatment for early stage non-small-cell lung cancer (NSCLC). For medically inoperable patients, stereotactic ablative radiotherapy (SABR) has emerged as widely used standard treatment. The aim of this study was to analyze survival and patterns of tumor recurrence in patients with clinical stage I NSCLC treated with surgery or SABR. Clinical data from all subsequent fluoro-deoxyglucose positron emission tomography/computed tomography-based stage I NSCLC patients (cT1-T2aN0M0) treated with surgery or SABR at our center between 2007 and 2010 were collected. Primary endpoints were overall survival and tumor recurrences/new primary lung tumors. Treatment groups were compared using multivariable Cox regression and competing risk analyses. Three hundred-forty patients treated with surgery (n = 143) or SABR (n = 197) were included. Surgical patients were younger, had a better WHO performance status and less comorbidities. After adjustment for prognostic covariables, treatment did not influence overall survival (adjusted hazard ratio [HR], SABR versus surgery 1.07; 95% confidence interval [CI]: 0.74-1.54; p = 0.73). Local control and distant recurrence were equal, whereas locoregional recurrences were significantly more frequent after SABR compared with surgery (adjusted sub-HR 2.51; 95% CI: 1.10-5.70; p = 0.028). Nodal failure (HR: 2.16; 95% CI: 1.34-3.48) and distant metastases (HR: 2.12; 95% CI: 1.52-2.97), but not local failure (HR: 1.00; 95% CI: 0.53-1.89) predicted overall survival. In patients with fluoro-deoxyglucose positron emission tomography/computed tomography-based stage I NSCLC, SABR confers worse locoregional tumor control because of more nodal failures compared with surgery, stressing the need to improve mediastinal and hilar staging.

Abstract S5-07: A randomized, open-label, multicenter, phase 3 study of epoetin alfa (EPO) plus standard supportive care versus standard supportive care in anemic patients with metastatic breast cancer (MBC) receiving standard chemotherapy

Abstract Background: Several investigational studies including MBC reported that erythropoiesis-stimulating agent (ESA) treatment beyond correction of anemia decreased survival and locoregional tumor control, and/or increased adverse effects, especially thrombotic vascular events (TVEs). These studies were reviewed at 3 FDA Oncologic Drugs Advisory Committee Meetings (2004, 2007, and 2008). Other studies and well-conducted meta-analyses did not suggest adverse effects on tumor outcomes when ESAs are used according to the prescribing information in subjects receiving chemotherapy, however, no study rigorously evaluated tumor outcomes. This Phase 3 study is the largest MBC trial in subjects receiving EPO for chemotherapy induced anemia specifically designed and conducted to assess progression-free survival (PFS) as the primary endpoint. Conducted as a post-marketing requirement, the study has been regularly and intensively monitored by an Independent Data Monitoring Committee (IDMC) of internationally recognized experts in the fields of MBC treatment, clinical research, and statistics. Methods: EPO-ANE-3010 (ClinicalTrials.gov #NCT00338286) is a multinational (19 countries and 223 participating sites) study with 2,098 subjects who are anemic and receiving first- or second-line standard chemotherapy for MBC. Key inclusion criteria: histologically confirmed MBC, stage IV disease and at least 1 measurable metastatic lesion according to Response Evaluation Criteria in Solid Tumors (RECIST); hemoglobin (Hb) ≤11 g/dL, Eastern Cooperative Oncology Group performance score 0 or 1. Key exclusion criteria: metastasis to bone only, receiving anticoagulants or endocrine therapy. Subjects were randomly assigned (1:1) to receive either standard supportive care for treatment of anemia (SOC) plus 40,000 IU EPO given subcutaneously weekly up to 4 weeks after the last dose of cytotoxic chemotherapy, or to SOC alone. Randomization was stratified by line of chemotherapy and HER2/NEU status. EPO dose was held for Hb &amp;gt;12 g/dL. Disease was assessed every 8 weeks for the first year, and then every 12 weeks until disease progression (PD) or death. Tumor response was determined according to modified RECIST 1.0 criteria by Investigators and Blinded Central Review. Overall survival (OS) follow up continued after PD. The primary endpoint is PFS. Secondary endpoints include OS, time to tumor progression, and overall response rate and safety assessments (including incidence and severity of TVEs). For this non-inferiority study, a sample size of 1,650 disease progression or death events was determined to provide over 80% power to rule out a 15% hazard rate increase (i.e., hazard ratio of 1.15, epoetin alfa vs. control) in PFS with a 1-sided Type I error rate 0.025. The study is fully accrued with 2014 projected key dates: clinical cut-off at 1650 PFS events, July; database lock, September; IDMC agreement on presentation of final results, mid-November. Both primary and secondary endpoints will be fully reported. Citation Format: Brian Leyland-Jones, Igor Bondarenko, Gia Nemsadze, Vitaliy Smirnov, Iryna Litvin, Irakli Kokhreidze, Lia Abshilava, Mikheil Janjalia, Rubi Li, KC Lakshmaiah, Beka Samkharadze, Oksana Tarasova, Ranjan Kumar Mohapatra, Yaroslav Sparyk, Sergey Polenkov, Vladimir Vladimirov, Liang Xiu, Bruce Kimelblatt, Kris Deprince, Ilya Safonov, Els Vercammen, Peter Bowers. A randomized, open-label, multicenter, phase 3 study of epoetin alfa (EPO) plus standard supportive care versus standard supportive care in anemic patients with metastatic breast cancer (MBC) receiving standard chemotherapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S5-07.

IAEA-HypoX. A randomized multicenter study of the hypoxic radiosensitizer nimorazole concomitant with accelerated radiotherapy in head and neck squamous cell carcinoma

PurposeTo test the hypothesis that radiotherapy (RT) of head and neck squamous cell carcinoma (HNSCC) can be improved by hypoxic modification using nimorazole (NIM) in association with accelerated fractionation. Materials and methodsThe protocol was activated in March 2012 as an international multicenter randomized trial in patients with HNSCC. Tumors were treated to a dose of 66–70Gy, 33–35 fractions, 6 fractions per week. NIM was administered in a dose of 1.2gperm2, 90min before the first daily RT fraction. The primary endpoint was loco-regional failure. The trial was closed prematurely by June 2014 due to poor recruitment. An associated quality assurance program was performed to ensure the consistency of RT with the protocol guidelines. ResultsThe trial was dimensioned to include 600 patients in 3years, but only 104 patients were randomized between March 2012 and May 2014 due to the inability to involve three major centers and the insufficient recruitment rate from the other participating centers. Twenty patients from two centers had to be excluded from the analysis due to the unavailability of the follow-up data. Among the remaining 84 patients, 82 patients were evaluable (39 and 43 patients in the RT+NIM and the RT-alone arms, respectively). The treatment compliance was good with only six patients not completing the full planned RT course, and 31 patients (79%) out of 39 allocated for NIM, achieving at least 90% of the prescribed drug dose. At the time of evaluation, 40 patients had failed to achieve persistent loco-regional tumor control, and a total of 45 patients had died. The use of NIM improved the loco-regional tumor control with an 18month post-randomization cumulative failure rate of 33% versus 51% in the control arm, yielding a risk difference of 18% (CI −3% to 39%; P=0.10). The corresponding values for overall death was 43% versus 62%, yielding a risk difference of 19% (CI −3% to 42%; P=0.10). Sixteen patients, out of 55 patients analyzed for hypoxic gene expression, were classified as having more hypoxic tumors. Such patients, if treated with RT alone, had a higher loco-regional tumor failure rate as compared to the rest of the patients with known hypoxic status (P=0.05). ConclusionAlthough the trial was incomplete and suffered from a small number of patients, the results suggested an improvement in loco-regional tumor control and overall survival in patients with advanced HNSCC given the hypoxic modifier NIM in addition to accelerated fractionation RT. However, the trial also revealed that conducting multicenter and multinational study combining drug and RT in developing countries may suffer from uncontrolled and unsolvable problems.

Prognostic factors and sites of metastasis in unresectable locally advanced pancreatic cancer.

Due to differences in natural history and therapy, clinical trials of patients with advanced pancreatic cancer have recently been subdivided into unresectable locally advanced pancreatic cancer (LAPC) and metastatic disease. We aimed to evaluate prognostic factors in LAPC patients who were treated with first-line chemotherapy and describe patterns of disease progression. Patients with LAPC who initiated first-line palliative chemotherapy, 2001–2011 at the BC Cancer Agency were included. A retrospective chart review was conducted to identify clinicopathologic variables, treatment, and subsequent sites of metastasis. Kaplan–Meier and Cox-regression survival analyses were performed. A total of 244 patients were included in this study. For the majority of patients (94.3%), first-line therapy was single-agent gemcitabine. About 144 (59%) patients developed distant metastatic disease and the most frequent metastatic sites included peritoneum/omentum (42.3%), liver (41%), lungs (13.9%), and distant lymph nodes (9%). Median overall survival (OS) for the entire cohort was 11.7 months (95% CI, 10.6–12.8). Development of distant metastases was associated with significantly inferior survival (HR 3.56, 95% CI 2.57–4.93), as was ECOG 2/3 versus 0/1 (HR 1.69, 95% CI 1.28–2.23), CA 19.9 > 1000 versus ≤1000 (HR 1.59, 95% CI 1.19–2.14) and female gender, (HR 1.57, 95% CI 1.19–2.08). In this population-based study, 41% of LAPC patients treated with first-line chemotherapy died without evidence of distant metastases. Prognostic factors for LAPC were baseline performance status, elevated CA 19.9, gender, and development of distant metastasis. Results highlight the heterogeneity of LAPC and the importance of locoregional tumor control.

Clinical value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in evaluating relapsed and refractory nasopharyngeal carcinoma: A case report.

For patients with locoregionally advanced nasopharyngeal carcinoma (NPC), radiotherapy, chemotherapy and even targeted therapy are widely accepted treatments. These treatments, although they mostly achieve locoregional tumor control, they may also be associated with complex post-treatment changes, such as edema, loss of tissue planes, fibrosis, mucositis and scarring, which may interfere with the detection of local recurrence and the response to therapy. However, timely detection is crucial for deciding whether treatment modification or discontinuation is required. This is the case report of A 51-year-old nasopharyngeal carcinoma patient with cervical nodal metastases (CNM). Following radiotherapy, chemotherapy and targeted therapy, multislice spiral enhanced computed tomography (CT), enhanced magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT of the neck were performed to compare the extent of the CNM. The enhanced CT and MRI images were unremarkable, whereas the 18F-FDG PET/CT images revealed the exact recurrence or remission. Therefore, 18F-FDG PET/CT exhibits a better sensitivity and specificity for evaluating the response to combined treatment compared to CT and/or MRI.

Locally advanced head and neck cancer treated with accelerated radiotherapy, the hypoxic modifier nimorazole and weekly cisplatin. Results from the DAHANCA 18 phase II study

Purpose/Objective. A phase II clinical trial evaluating the feasibility and outcome of treating locally advanced head and neck squamous cell carcinoma (HNSCC) with accelerated radiotherapy, the hypoxic modifier nimorazole and weekly cisplatin.Material and methods. A total of 227 patients with stage III or IV HNSCC of the larynx, oropharynx, hypopharynx, or oral cavity where included between January 2007 and December 2010. The prescribed radiotherapy (RT) dose was 66–68 Gy in 2 Gy fractions, 6 F/W. The hypoxic radiosensitiser nimorazole was given orally at a dose of 1200 mg/m2 before each fraction. Concomitant cisplatin (40 mg/m2) i.v. was given once a week for a maximum of six cycles. Outcome data were evaluated in terms of loco-regional tumour control (LRC), event-free survival (EFS) and overall survival (OS). Morbidity data were evaluated based on the DAHANCA routine registration. Human papillomavirus (HPV)-status was estimated by immunohistochemical staining of p16.Results. Included were 178 (78%) men and 49 (22%) women with a median age of 57 years. All except five patients received RT as prescribed. At least five series of cisplatin was given to 164 (72%) of the patients, and 149 patients (66%) received the full dose of nimorazole. The five-year actuarial LRC, EFS and OS rates were 80%, 67% and 72%, respectively. The LRC rates according to site were: oropharynx: 88%, larynx: 77%, hypopharynx 72% and oral cavity 49%, respectively. HPV/p16 staining was obtained in 141 of the 150 oropharyngeal cancers. Of these, 112 (79%) were p16 pos and 29 (21%) were p16 neg. LRC for the p16 neg oropharyngeal cancers was poorer than for the p16 pos (74% vs. 91%; p = 0.02). Tube feeding during treatment was necessary for 146 (64%) patients. At 12 months this number was reduced to 6%.Conclusion. The treatment was tolerable in this cohort of locally advanced HNSCC patients. Acute and late toxicity was comparable to similar studies of chemoradiotherapy, and the outcome superior to the data reported in the literature. This strongly indicates that RT of advanced head and neck cancer must include as well hypoxic modification, accelerated fractionation as chemoradiotherapy to yield optimal outcome.

POSSIBILITIES OF THERAPY OF HER-2-POSITIVE REGIONAL BREAST CANCER

Breas t cancer heads the list of malignant neoplasms in women. In this connection the regional forms of cancer are diagnosed in one fourth of the patients. The treatment of regional cancer begins with systemic therapy and aimed at gaining of state fit for operation. The choice of modern treatment strategy is based on determination of molecular subtype of the tumor. One of them is referred to HER-2-positive cancer, requiring the administration of additional targeted therapy. This form of cancer is referred to prognostically pejorative tumors, as it’s more aggressive, leads to fast metastasis and early death of the patients. The “golden standard” of systemic chemotherapy is defined as administration of docetaxel and trastuzumab, and antracyclic drugs, which also prove to be efficient. However concomitant administration of trastuzumab and antracyclines is limited due to their cardiotoxicity. Chemotherapy is not always efficient and, upon recommendations both of Russian and international oncologists, radiotherapy is the next stage of treatment. The question about radiosensibility of HER-2-positive tumors is still open and worth studying. Addition of radiotherapy to regional cancer treatment regimen in combination with the targeted therapy and chemotherapy may contribute to obtaining better survival rate and disease control. There are still no clearly defined standard for the sequence of chemo-radiation therapy. Simultaneous chemo-radiatiojn therapy results in reliably better loco-regional control of tumor and enables to gain a higher degree of pathomorphological response on the one hand, and it may result in development of serious adverse effects on the other hand. Striving for improvement of immediate results of antineoplastic therapy, including that of regional cancer, by combining various methods, one should keep in mind the increasing action toxicity, which may have a considerable impact on the patients’ quality of living. Continuation of experiments and clinical trials in this direction is rather actual, as it allows getting new data for treatment of regional breast cancer.

Making Sense of the Advances in the Treatment of Hepatocellular Carcinoma

Recent advances in the understanding and management of hepatocellular carcinoma are promising and may usher in a new era in cancer therapy. Here we discuss the latest improvement in hepatitis C antiviral therapy, loco-regional tumor control, c-met inhibitors, and immune therapy. Genetic testing in hepatocellular carcinoma could be a turning point in the treatment development of this fatal disease.

HPV16 DNA status is a strong prognosticator of loco-regional control after postoperative radiochemotherapy of locally advanced oropharyngeal carcinoma: Results from a multicentre explorative study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)

ObjectiveTo investigate the impact of HPV status in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received surgery and cisplatin-based postoperative radiochemotherapy. Materials and methodsFor 221 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity treated at the 8 partner sites of the German Cancer Consortium, the impact of HPV DNA, p16 overexpression and p53 expression on outcome were retrospectively analysed. The primary endpoint was loco-regional tumour control; secondary endpoints were distant metastases and overall survival. ResultsIn the total patient population, univariate analyses revealed a significant impact of HPV16 DNA positivity, p16 overexpression, p53 positivity and tumour site on loco-regional tumour control. Multivariate analysis stratified for tumour site showed that positive HPV 16 DNA status correlated with loco-regional tumour control in patients with oropharyngeal carcinoma (p=0.02) but not in the oral cavity carcinoma group. Multivariate evaluation of the secondary endpoints in the total population revealed a significant association of HPV16 DNA positivity with overall survival (p<0.01) but not with distant metastases. ConclusionsHPV16 DNA status appears to be a strong prognosticator of loco-regional tumour control after postoperative cisplatin-based radiochemotherapy of locally advanced oropharyngeal carcinoma and is now being explored in a prospective validation trial.

Post-mastectomy Hypofractionation Radiotherapy in Breast Cancer Patients

Background: Post-mastectomy radiotherapy reduces loco-regional recurrence in women with operable breast cancer and improves survival. Conventional fractionated radiotherapy has been limited by patient's compliance, travelling, unplanned interruption and others. Hypofractionated schedule would be more appealing and convenient. The present study was carried out to compare overall survival, disease free survival, loco regional control, and treatment toxicities, in patients treated with conventional fractionated radiotherapy and hypofractionated schedules. Methods: Forty-seven patients with breast cancer (stage T2-4, any N), underwent surgery and received adjuvant systemic treatment and radiotherapy. These patients randomly divided into two groups; conventional fractionated radiotherapy group (N: 22), and hypofractionated radiotherapy group (N: 25). Data of radiation toxicities, and disease relapse in both groups were compared using Chi-square test. Results: The median follow-up was 34 months (range: 13 – 53 months). Four-year overall survival rates were 100% for conventional radiotherapy group and 96% for hypofractionated radiotherapy group, with no significant difference (P value= 0.37). The 4 year disease free survival rate were 81% and 92% for conventional radiotherapy group and hypofractionation radiotherapy group, respectively (p-value= 0.47) and hazard ratio= 0.52 (0.09-2.13). Toxicities were comparable between the both groups. Conclusions: these data showed that hypofractionation 42 Gy radiotherapy in 16 fractions was safe and comparable to conventional fractionation in terms of overall survival, loco-regional tumor control and toxicities. These results need to be tested in large-scale multicenter randomized control trials.

Incidence of Synchronous Intra-thoracic Malignancy in patients with Head and Cancer - is CT thorax justified?

Results: 48 patients (35 males/13 females) with an average age of 58 years received IMRT,8 with palliative intent. The majority of patients were staged at T4N2b disease. Simultaneous chemotherapy was given in 23 cases usually with cisplatin, 5FU or TPF. Total treatment dose ranged between 10-24 Grays in 5 fractions for palliative patients and 60 Grays in 30 fractions for patients treated with curative intent. Complications associated with IMRT included grade 2 mucositis (8), grade 2 skin reaction (3), grade 2 dysphagia (6), grade 3 mucositis (10),hypoacusis (5) trismus (2) and xerostomia (4).15 patients required inpatient admission for the management of their grade 3 mucositis and dehydration. Discussion: Surgery followed by post operative IMRT in patients with substantial risk of recurrence resulted in high loco-regional tumour control rates and decreased incidence of xerostomia.

DART-BID (Differentiated Accelerated Radiation Therapy–1.8 Gy Twice Daily) for Locoregionally Advanced NSCLC: Mature Results of a Novel Therapeutic Approach

DART-BID (Differentiated Accelerated Radiation Therapy–1.8 Gy Twice Daily) for Locoregionally Advanced NSCLC: Mature Results of a Novel Therapeutic Approach

IOERT as anticipated tumor bed boost during breast-conserving surgery after neoadjuvant chemotherapy in locally advanced breast cancer--results of a case series after 5-year follow-up.

To evaluate retrospectively rates of local (LCR) and locoregional tumor control (LRCR) in patients with locally advanced breast cancer (LABC) who were treated with preoperative chemotherapy (primary systemic treatment, PST) followed by breast-conserving surgery (BCS) and either intraoperative radiotherapy with electrons (IOERT) preceding whole-breast irradiation (WBI) (Group 1) or with WBI followed by an external tumor bed boost (electrons or photons) instead of IOERT (Group 2). From 2002 to 2007, 83 patients with clinical Stage II or III breast cancer were enrolled in Group 1 and 26 in Group 2. All patients received PST followed by BCS and axillary lymph node dissection. IOERT boosts were applied by single doses of 9 Gy (90% reference isodose) versus external boosts of 12 Gy (median dose range, 6-16) in 2 Gy/fraction (ICRU). WBI in both groups was performed up to total doses of 51-57 Gy (1.7-1.8 Gy/fraction). The respective median follow-up times for Groups 1 and 2 amount 59 months (range, 3-115) and 67.5 months (range, 13-120). Corresponding 6-year rates for LCR, LRCR, metastasis-free survival, disease-specific survival and overall survival were 98.5, 97.2, 84.7, 89.2 and 86.4% for Group 1 and 88.1, 88.1, 74, 92 and 92% for Group 2, respectively, without any statistical significances. IOERT as boost modality during BCS in LABC after PST shows a trend to be superior in terms of LCR and LRCR in comparison with conventional boosts.

Locoregional Control of Non-Small Cell Lung Cancer in Relation to Automated Early Assessment of Tumor Regression on Cone Beam Computed Tomography

Large interindividual variations in volume regression of non-small cell lung cancer (NSCLC) are observable on standard cone beam computed tomography (CBCT) during fractionated radiation therapy. Here, a method for automated assessment of tumor volume regression is presented and its potential use in response adapted personalized radiation therapy is evaluated empirically. Automated deformable registration with calculation of the Jacobian determinant was applied to serial CBCT scans in a series of 99 patients with NSCLC. Tumor volume at the end of treatment was estimated on the basis of the first one third and two thirds of the scans. The concordance between estimated and actual relative volume at the end of radiation therapy was quantified by Pearson's correlation coefficient. On the basis of the estimated relative volume, the patients were stratified into 2 groups having volume regressions below or above the population median value. Kaplan-Meier plots of locoregional disease-free rate and overall survival in the 2 groups were used to evaluate the predictive value of tumor regression during treatment. Cox proportional hazards model was used to adjust for other clinical characteristics. Automatic measurement of the tumor regression from standard CBCT images was feasible. Pearson's correlation coefficient between manual and automatic measurement was 0.86 in a sample of 9 patients. Most patients experienced tumor volume regression, and this could be quantified early into the treatment course. Interestingly, patients with pronounced volume regression had worse locoregional tumor control and overall survival. This was significant on patient with non-adenocarcinoma histology. Evaluation of routinely acquired CBCT images during radiation therapy provides biological information on the specific tumor. This could potentially form the basis for personalized response adaptive therapy.