Inferior Local Control Research Articles

Immunohistochemical overexpression of hypoxia-induced factor 1α associated with slow reduction in 18fluoro-2-deoxy-D-glucose uptake for chemoradiotherapy in patients with pharyngeal cancer.

This study examined genomic factors associated with a reduction in 18fluoro-2-deoxy-D-glucose (FDG) uptake during positron emission tomography-computed tomography (PET-CT) for definitive chemoradiotherapy (CRT) in patients with pharyngeal cancer. The pretreatment and interim PET-CT images of 25 patients with advanced pharyngeal cancers receiving definitive CRT were prospectively evaluated. The maximum standardized uptake value (SUVmax) of the interim PET-CT and the reduction ratio of the SUVmax (SRR) between the two images were measured. Genomic data from pretreatment incisional biopsy specimens (SLC2A1, CAIX, VEGF, HIF1A, BCL2, Claudin-4, YAP1, MET, MKI67, and EGFR) were analyzed using tissue microarrays. Differences in FDG uptake and SRRs between tumors with low and high gene expression were examined using the Mann-Whitney test. Cox regression analysis was performed to examine the effects of variables on local control. The SRR of the primary tumors (SRR-P) was 0.59 ± 0.31, whereas the SRR of metastatic lymph nodes (SRR-N) was 0.54 ± 0.32. Overexpression of HIF1A was associated with a high iSUVmax of the primary tumor (P < 0.001) and neck lymph node (P = 0.04) and a low SRR-P (P = 0.02). Multivariate analysis revealed that patients who had tumors with low SRR-P or high HIF1A expression levels showed inferior local control. In patients with pharyngeal cancer requiring CRT, HIF1A overexpression was positively associated with high interim SUVmax or a slow reduction in FDG uptake. Prospective trials are needed to determine whether the local control rate can be stratified using the HIF1A level as a biomarker and SRR-P.

Local Control With 21-Gy Radiation Therapy for High-Risk Neuroblastoma

To evaluate local control after 21-Gy radiation therapy (RT) to the primary site in patients with high-risk neuroblastoma. After receiving dose-intensive chemotherapy and gross total resection (GTR), 246 patients (aged 1.2-17.9years, median 4.0years) with high-risk neuroblastoma underwent RT to the primary site at Memorial Sloan Kettering from 2000 to 2014. Radiation therapy consisted of 21Gy in twice-daily fractions of 1.5Gy each. Local failure (LF) was correlated with biologic prognostic factors and clinical findings at the time of diagnosis and start of RT. Median follow-up of surviving patients was 6.4years. Cumulative incidence of LF was 7.1% at 2years after RT and 9.8% at 5years after RT. The isolated LF rate was 3.0%. Eighty-six percent of all local failures were within the RT field. Local control was worse in patients who required more than 1 surgical resection to achieve GTR (22.4% vs 8.3%, P=.01). There was also a trend toward inferior local control with MYCN-amplified tumors or serum lactate dehydrogenase ≥1500 U/L (P=.09 and P=.06, respectively). After intensive chemotherapy and maximal surgical debulking, hyperfractionated RT with 21Gy in high-risk neuroblastoma results in excellent local control. Given the young patient age, concern for late effects, and local control >90%, dose reduction may be appropriate for patients without MYCN amplification who achieve GTR.

Volumetric modulated arc radiotherapy of the whole larynx, followed by a single affected vocal cord, for T1a glottic cancer: Dosimetric analysis of a case.

Radiation therapy (RT) and endolaryngeal surgery are standard treatments for early-stage glottic cancer. They have closely matched oncological outcomes; however, it is debatable which method is superior in terms of functional outcomes. Several dosimetric studies have demonstrated that, compared with conventional RT, intensity-modulated RT (IMRT) reduces unnecessary radiation of the adjacent normal tissues, including the carotid artery and thyroid gland. However, RT targets the whole larynx, whereas endolaryngeal surgery is a highly focused treatment involving the en bloc resection of a tumor with safety margins. For T1a glottic cancer, in which the tumor is limited to one vocal cord, the technical feasibility of targeting IMRT on the single vocal cord affected has been investigated; however, the clinical feasibility and the possibility of inferior local control remain to be elucidated. In the present case study, IMRT was used to treat the whole larynx first, and then to treat a single vocal cord. The patient in the present study had T1a glottic cancer, and received volumetric modulated arc therapy with a total dose of 63 Gy/28 fractions. The first treatment phase (40.5 Gy/18 fractions) targeted the whole larynx to eliminate subclinical disease. The second treatment phase (22.5 Gy/10 fractions) targeted only the involved vocal cord. During this treatment phase, the exposure of the non-involved right vocal cord, the right carotid artery and the thyroid gland to the radiation was lower compared with the continuation of the initial treatment approach. These findings suggested that changing the target volume from the whole larynx to the affected vocal cord during the course of IMRT is feasible for T1a glottic cancer, and that it may reduce functional side effects while maintaining oncological outcomes.

Balloon-Occluded Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: A Single-Center Experience

Objective: To investigate whether balloon-occluded transcatheter arterial chemoembolization (b-TACE) can produce a more dense accumulation of iodized oil in various stages of hepatocellular carcinoma (HCC), from single to uncountable, to overcome inferior local control. Materials and Methods: We studied 27 patients with HCC, including single to uncountable multiple lesions, who underwent b-TACE between August 2013 and April 2015. Dynamic CT was performed at baseline and 1-3 months after b-TACE. The treatment effect (TE) after b-TACE was evaluated using the Response Evaluation Criteria in Cancer of the Liver (RECICL) proposed by the Liver Cancer Study Group of Japan. Results: In the countable HCC group, contrast-enhanced CT demonstrated RECICL TE4 in 43.8% (14/32), TE3 in 12.5% (4/32), TE2 in 37.5% (12/32), and TE1 in 6.3% (2/32) of patients. For the TACE-naïve cohort, the objective response rate was 52.9%. The objective response rate was 60% for the previously TACE-treated cohort. In the uncountable multiple HCC group, the objective response rate was 0% (0/10), with progressive disease in 90% (9/10) of patients. Conclusion: Our observations suggested that b-TACE did not reduce the efficacy of retreatment for HCC with an insufficient outcome from conventional TACE, but it could not improve the efficacy of treatment for uncountable multiple HCCs.

Local Control Following Postoperative Stereotactic Radiation Therapy for Brain Metastases

Stereotactic radiosurgery (SRS) and fractionated stereotactic radiation therapy (FSRT) have emerged as viable alternatives to whole brain radiation therapy (WBRT) in patients with resected brain metastases. We performed a systematic review and quantitative analysis of the published experiences with adjuvant SRS and FSRT to determine local control (LC) rates and any relationship with dose-response, fractionation, and treatment delivery parameters. We identified published articles that reported local control rates following post-operative SRS or FSRT to the resection cavity in patients with brain metastases. For series in which uniform dosing schedules were used, biologically effective doses (BED) were calculated using the linear quadratic model and assuming an α/β ratio of 10 Gy. Local control data for the individual resection cavities treated in each study were extracted from actuarial survival curves and aggregated to form a single dataset. Kaplan-Meier curves for local control in the entire dataset and after grouping by treatment platform, fractionation, use of margin expansion, and BED were generated, and statistical comparisons were made using the log-rank test. Seventeen studies (1104 patients with 1155 resection cavities) met all inclusion criteria. Median dose for single fraction regimens was 14-20 Gy, while FSRT was used in 8 studies with regimens ranging from 9 Gy x 3 to 4 Gy x 10 (BED range of 41 Gy10 to 56 Gy10). One and two-year actuarial LC rates for the entire cohort were 83% and 75%, respectively. FSRT was associated with slightly higher one-year (87% v. 81%) and two-year (78% v. 73%) actuarial LC rates than SRS (p=0.049). For patients treated with SRS, use of Gamma Knife was associated with inferior LC compared to treatment with linear accelerator-based platforms (p=0.002). There was no association between use of a planning margin and LC. Most SRS series utilized a wide range of doses, so dose-response analysis could not be performed. In FSRT series, there was no significant association between BED and LC. The overall toxicity rate, which predominantly included radiation necrosis, was approximately 7% and not significantly different between treatment platforms or fractionation schemes. Adjuvant SRS and FSRT provide high rates of local control following resection of brain metastases. FSRT should be considered in cases where therapeutic doses cannot be safely delivered in a single fraction. Prospective trials are warranted to further characterize the optimal regimen and treatment parameters.

Conservative surgery for multifocal/multicentric breast cancer

Multifocal (MF) and multicentric (MC) breast cancer is regularly considered a relative contraindication for breast-conserving therapy (BCT). There are two reasons for this wide spread notion:1.Perceived higher risk for in-breast recurrence since it is assumed that in MF/MC cancer the risk of more invasive foci in the breast is greater, and therefore radiotherapy possibly less effective.2.Less good cosmetic outcome due to wider excisions, either segmental resection or quadrantectomy in multifocal, or multiple wide local excisions in multicentric disease.However, we concur that if optimal ‘cytoreductive surgery’ is achieved this will result in good local control (i.e. in-breast relapse <10% at 10 years). This can only be achieved on the basis of the right imaging, image guidance for non-palpable foci, and tumor free (invasive as well as ductal carcinoma in situ) margins after adequate pathological assessment. Surgery must then be followed by whole breast irradiation and systemic treatments as indicated by primary cancer biology. Careful planning and adaptive application of oncoplastic techniques will result in an optimal cosmetic results.The meticulous work of Roland Holland and coworkers1 in the early 1980’s on whole breast specimen showed invasive foci at more then 2 cm distance from the invasive primary cancer in more then 40% of specimen. Although multiple tumor foci may occur in up to 60% of mastectomy specimens, equivalent survival outcomes were observed in prospective trials comparing BCT and mastectomy for clinically unifocal lesions, suggesting that the majority of these foci are not, or do not become, biologically relevant or clinically significant with appropriate treatment.As diagnostic tools advance, MF and MC tumors are more commonly diagnosed. Cancers that previously would have been classified as unifocal now can be detected as MF or MC. In addition, locoregional treatment modalities have improved significantly over the past decade. More recent studies reflect these advances in diagnosis and treatment. Studies evaluated staging MRI showed that up to 19% of woman with diagnosed breast cancer harbor a second malignant ipsilateral lesion. These findings should only have consequences when additional lesions are proven cancer. Multiple enhancing lesions on MRI are in itself not an indication for a mastectomy.The Z0011 trial and the AMAROS trial demonstrated a similar phenomenon for axillary treatment; less surgery does not necessarily lead to inferior local control or survival outcomes. Recent studies supplement the growing evidence that treatment of patients with MF/MC breast cancer with BCS, radiotherapy, and adjuvant systemic therapy can result in low rates of in-breast recurrence.

Impact of resection margin status on outcome after salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma.

The purpose of this study was to present the postoperative local tumor control and survival with regard to the different resection margin statuses during salvage nasopharyngectomy. We conducted a whole-organ study of nasopharyngectomy specimens. Between 2005 and 2010, 126 patients underwent maxillary swing nasopharyngectomy. The T classification of the recurrent tumor was: T1, 23.8%; T2, 41.3%; T3, 28.6%; and T4, 6.3%. The chance of clear, close, and involved resection margins at nasopharyngectomy was 44.4%, 31.0%, and 24.6%, respectively. At follow-up, the corresponding risk of local tumor recurrence after surgery was 10.7%, 38.5%, and 67.7%, respectively. The local tumor control was significantly worse in patients with involved margins compared with those with close margins (p = .01), which was, in turn, significantly worse than those with clear margins (p = .04). The primary objective of salvage nasopharyngectomy is to achieve clear resection margins. Close and involved margins result in significantly inferior local tumor control and overall survival. © 2015 Wiley Periodicals, Inc. Head Neck 38: E594-E599, 2016.

Central versus Peripheral Tumor Location: Influence on Survival, Local Control, and Toxicity Following Stereotactic Body Radiotherapy for Primary Non–Small-Cell Lung Cancer

Stereotactic body radiotherapy (SBRT) has been increasingly utilized for medically inoperable early stage non-small-cell lung cancer. However, a lower biological equivalent dose (BED) is often used for central tumors given toxicity concerns, potentially leading to decreased local control (LC). We compared survival, LC, and toxicity outcomes for SBRT patients with centrally versus peripherally located tumors. We included patients with primary cT1-2N0M0 non-small-cell lung cancer treated with SBRT at our institution from September 2007 to August 2013 with follow-up through August 2014. Central tumor location was defined as within 2 cm of the proximal bronchial tree, heart, great vessels, trachea, or other mediastinal structures. Kaplan-Meier analysis and multivariable Cox regression modeling were used for overall survival (OS) and LC, and the χ test and multivariable logistic regression modeling were used for toxicity. We included 251 patients (111 central, 140 peripheral) with median follow-up of 31.2 months. Patients with central tumors were more likely to be older (mean 75.8 versus 73.5 years; p = 0.04), have larger tumors (mean 2.5 cm versus 1.9 cm; p < 0.001), and be treated with a lower BED (mean 120.2 Gy versus 143.5 Gy; p < 0.001). Multivariable analysis revealed that tumor location was not associated with worse OS, LC, or toxicity. Patients with central tumors were less likely to have acute grade greater than or equal to three toxicity than those with peripheral tumors (odds ratio: 0.24; p = 0.02). Central tumor location did not predict for inferior OS, LC, or toxicity following SBRT when a lower mean BED was utilized.

Cervical cancer outcome prediction to high-dose rate brachytherapy using quantitative magnetic resonance imaging analysis of tumor response to external beam radiotherapy

Background and purposeIn order to assess tumor regression and outcomes, a volumetric analysis was conducted for cervical cancer patients treated with magnetic resonance imaging (MRI)-based image-guided brachytherapy (IGBT). Materials and methodsConsecutive patients with FIGO stage IB1–IVA cervical cancer receiving chemoradiation from 2007 to 2013 were identified, excluding patients with perineal template-based interstitial brachytherapy or without undergoing MRI. A ring and tandem applicator±interstitial needles was used. T2-weighted imaging was completed following applicator insertion. Gross tumor volumes (GTVs) were retrospectively contoured: initial GTV (GTVPre-EBRT), GTV at first brachytherapy (GTVIGBT) and percent residual GTV at first brachytherapy (% GTVResidual). ResultsEighty-four patients were identified. With 20.8-month median follow-up, two-year estimates of local control (LC), disease-free survival (DFS) and overall survival (OS) were 91.3, 79.8, and 85.0%, respectively. Multivariate Cox regression revealed adenocarcinoma (HR 5.88, p=0.03) and GTVIGBT (HR 1.17, p<0.01) as predictors for local failure. GTVIGBT>7.5cc was associated with inferior 2-year LC (75.0 vs. 96.6%, p<0.01), DFS (42.6 vs. 91.6%, p<0.01) and OS (65.2 vs. 91.5%, p<0.01). No difference in mean HRCTV D90 EQD2 was seen between the groups (p=0.61). ConclusionAside from known benefits of IGBT, MRI-based planning allows for assessment of tumor regression and prognosticates patients.

Outcomes and prognostic factors for Ewing-family tumors of the extremities.

There are few published studies describing the clinical results of patients uniformly treated for a Ewing-family tumor of an extremity. We performed a review of patients who had received uniform treatment consisting of neoadjuvant chemotherapy, surgery and/or radiation therapy as local treatment, and then adjuvant chemotherapy from June 2003 to November 2011 at a single institution. There were 158 patients included in the study. The median age was fifteen years. Sixty-nine (44%) of the patients had metastatic disease at presentation. Fifty-seven patients underwent surgery, and forty-one received radical radiation therapy following neoadjuvant chemotherapy. After a median of 24.3 months (range, 1.6 to ninety-seven months) of follow-up, the five-year event-free survival, overall survival, and local control rates (and standard error) were 24.1% ± 4.3%, 43.5% ± 6%, and 55% ± 6.8%, respectively, for the entire cohort and 36.4% ± 6.2%, 57.6% ± 7.4%, and 58.2% ± 7.9%, respectively, for patients without metastases. In the multivariate analysis, metastases predicted inferior event-free survival (p = 0.02) and overall survival (p = 0.03) rates in the entire cohort, whereas radical radiation therapy predicted an inferior local control rate in the entire cohort (p = 0.001) and in patients without metastases (p = 0.04). In the group with localized disease, there was no difference between the patients who received radical radiation therapy and those who underwent surgery with regard to tumor diameter (p = 0.8) or post-neoadjuvant chemotherapy response (p = 0.1). A white blood cell count (WBC) of &gt;11 × 109/L predicted inferior event-free survival (p = 0.005) and local control (p = 0.02) rates for patients without metastases. To our knowledge, this is the largest study on extremity Ewing-family tumors treated with uniform chemotherapy and either surgical resection or radical radiation therapy in Asia. All possible efforts should be made to resect a primary tumor after neoadjuvant chemotherapy, as radical radiation therapy alone results in a poor local control rate despite a good post-neoadjuvant chemotherapy response. Patients without metastases but with a high WBC had inferior event-free survival and local control rates and may require more aggressive therapy. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Inferior local control for T2bN0 glottic carcinoma with impaired mobility treated with radiation alone: A need for more chemotherapy?

6084 Background: Radiation therapy monotherapy (RT) is standard for patients (pts) with T2N0 squamous cell cancer (SCC) of the glottis. The presence of impaired vocal cord mobility (T2b) is known t...

Local recurrence and survival following stereotactic radiosurgery for brain metastases from small cell lung cancer

PurposeStereotactic radiosurgery (SRS) represents a treatment option for patients with brain metastases from small cell lung cancer (SCLC) following prior cranial radiation. Inferior local control has been described. We reviewed our failure patterns following SRS treatment to evaluate this concern. Methods and materialsIndividuals with SCLC who received SRS for brain metastases from 2004 to 2011 were identified. Central nervous system (CNS) disease was detected and followed by gadolinium-enhanced, high-resolution magnetic resonance (MR) imaging. SRS dose was prescribed to the tumor periphery. Local recurrence was defined by increasing lesion size or enhancement, MR-spectroscopy, and perfusion changes consistent with recurrent disease or pathologic confirmation. Any new enhancing lesion not identified on the SRS planning scan was considered a regional failure. Overall survival (OS) and CNS control were evaluated using the Kaplan-Meier method. Factors predicted to influence outcome were tested by univariate log-rank analysis and Cox regression. ResultsFifteen males and 25 females (median age of 61 years [range, 36-79]) of which 39 received prior brain irradiation were identified. In all, 132 lesions (3.3 per patient) between 0.4 and 4.7 cm received a median dose of 16 Gy (12-22 Gy). Thirteen metastases (10%) ultimately recurred locally with 6- and 12-month control rates of 81% and 69%, respectively. Only 1 of 110 metastases <2 cm recurred. Local failure was more likely for size >2 cm (P < .001) and dose <16 Gy (P < .001). The median OS was 6.5 months, and the time to regional CNS recurrence was 5.2 months. For patients with single brain metastases, both OS (P = .037) and regional CNS recurrence (P = .003) were improved. CNS control (P = .001), and survival (P = .057), were also longer for patients with controlled systemic disease. ConclusionsLocal control following SRS for SCLC metastases is achievable for lesions <2 cm. For metastases >2 cm, local failure is more common than expected. Patients with controlled systemic disease and limited CNS involvement would benefit most from aggressive treatment.

Dysplasia at the margin? Investigating the case for subsequent therapy in ‘Low-Risk’ squamous cell carcinoma of the oral tongue

This is a retrospective analysis of the impact of moderate dysplasia at the resection margin for early stage cancer of the oral tongue. Patients with T1-2N0 oral tongue cancer treated with surgery alone at Fox Chase Cancer Center (FCCC) from 1990 to 2010 were reviewed. Tumor and margin characteristics were abstracted from the pathology report. Overall survival (OS), disease-free survival (DFS) and local control (LC) were calculated using the Kaplan Meier method. Predictors of LC, OS and DFS were analyzed. 126 Patients met the inclusion criteria. Dysplasia was present at the final margin in 36% of the cases (severe: 9%, moderate: 15%, mild: 12%). Median follow-up was 52 months. 3 and 5-year actuarial LC for the entire cohort was 77% and 73%, respectively. Actuarial 5-year LC and DFS were significantly worse for patients with moderate or severe dysplasia at the margin vs. none or mild dysplasia at the margin (49% vs 82%, p=0.005 and 49% vs 80%, p=0.008, respectively); 3-year comparisons were not significant. When analyzed separately, the detrimental local effect of moderate dysplasia at the margin persisted (p=0.02) and the effect of severe dysplasia at the margin was approaching significance (p=0.1). Mild dysplasia at the margin did not significantly impair LC or DFS. Multivariate analysis demonstrated worse LC (HR: 2.99, p=0.006) and DFS (HR: 2.84, p=0.008) associated with severe or moderate dysplasia at the margin. Both severe and moderate dysplasia at the margin appear to be correlated with inferior LC and DFS. Additional therapy may be justified, despite added morbidity.

Oncologic outcomes of transoral laser microsurgery for radiorecurrent laryngeal carcinoma: A systematic review and meta‐analysis of English‐language literature

The purpose of this systematic review and meta-analysis was to assess the oncological and functional outcomes of transoral laser microsurgery (TLM) in radiorecurrent laryngeal cancer. The review was performed using search strategies including Medline, Embase, Zetoc, conference proceedings, and a manual search. Pooled estimates of local control at 24 months, disease-free survival (DFS), and overall survival (OS) rates were calculated. The pooled mean estimates were: local control rate at 24 months after first TLM (n = 249), 56.9% (95% confidence interval [CI], 47.4-66.1); local control after repeat TLM (n = 186), 63.8% (95% CI, 57.1-70.2); DFS (n = 174), 70.9% (95% CI, 60.8-80); and OS (n = 276), 74.8% (95% CI, 68.2-80.9). Pooled mean laryngeal preservation (n = 286) was 72.3% (95% CI, 68.4-76.1). TLM is oncologically sound in the salvage setting with high larynx-preservation rate, but there is a trend toward inferior local control rates compared to open partial laryngectomy techniques.

HPV status to predict outcome for anal cancer treated with radiochemotherapy.

4065 Background: Evaluation of the HPV infection- and transformation-status as a predictor of the response to definitive radio-chemotherapy for anal cancer. Methods: 80 patients (54 fm, 26 m) with histologically confirmed anal cancer and known HPV-Infection- (determined by PCR) and p16-expression-status (determined by immunohistochemistry) were analyzed. All pts. were treated with definitive radio-chemotherapy (RCT) with 5-FU/MMC, median age 60ys (35–86), median follow up 54mo (4–180). 41 pts. were HPV+ and p16+ (group 1), 10 pts. were HPV-/p16+ (group 2), 9 pts. were HPV+/p16- (group 3) and 17 pts. were HPV+/p16- (group 4). Endpoints were local control (LC) at 5ys and overall survival (OS) at 5ys. In addition to HPV/p16 status, the influence of T-stage and tumor localization (canal vs. margin) was analyzed. Results: More women than men were HPV+ (fm 77% vs. m 33%) while gender was evenly distributed among HPV-pts. (fm 48% vs. m 53%). Upon univariate analysis, gender, HPV+ and p16+ were significant predictors of both LC and OS (p&lt;0.05) while T-Stage was predictive for LC (p&lt;0.05). Upon multivariate analysis, gender and T-Stage significantly influenced LC (w85.2% vs. m54.9%, p=0.028; &lt;T3 84.2% vs ≥ T3 48,1%, p=0,019). OS was significantly influenced by gender (w95% vs. m59.2%, p=0.005), while the influence of HPV/p16-status did not reach significance when all four groups were analyzed simultaneously in this moderately sized cohort. Upon direct univariate comparison of HPV+/p16+ und HPV-/p16-pts, both gender and combined HPV/p16-positivity had a significant influence on LC and OS. Upon multivariate analysis, combined HPV/p16-positivity resulted in better LC (HPV+/p16+: 85% vs. HPV-/p16-: 38.7%, p=0.003), while, as a consequence of moderate patient numbers, only gender significantly predicted OS (fm93.7% vs. m62.6%, p=0.015). Viral status, however, showed a trend for significance. Conclusions: The data from one of the largest monocentric series treated with a uniform treatment regimen suggest that HPV-status predicts response to RCT in pts. with anal cancer. Patients with tumors not associated with HPV whatsoever (HPV-/P16-) have both inferior LC and a clear trend for inferior OS and might require an intensified treatment regimen.

Superior prognostic utility of gross and metabolic tumor volume compared to standardized uptake value using PET/CT in head and neck squamous cell carcinoma patients treated with intensity-modulated radiotherapy

ObjectiveTo compare the prognostic utility of the 2-[18F] fluoro-2-deoxy-d-glucose (FDG) maximum standardized uptake value (SUVmax), primary gross tumor volume (GTV), and FDG metabolic tumor volume (MTV) for disease control and survival in patients with head and neck squamous cell carcinoma (HNSCC) undergoing intensity-modulated radiotherapy (IMRT).MethodsBetween 2007 and 2011, 41 HNSCC patients who underwent a staging positron emission tomography with computed tomography and definitive IMRT were identified. Local (LC), nodal (NC), distant (DC), and overall (OC) control, overall survival (OS), and disease-free survival (DFS) were assessed using the Kaplan–Meier product-limit method.ResultsWith a median follow-up of 24.2 months (range 2.7–56.3 months) local, nodal, and distant recurrences were recorded in 10, 5, and 7 patients, respectively. The median SUVmax, GTV, and MTV were 15.8, 22.2 cc, and 7.2 cc, respectively. SUVmax did not correlate with LC (p = 0.229) and OS (p = 0.661) when analyzed by median threshold. Patients with smaller GTVs (<22.2 cc) demonstrated improved 2-year actuarial LC rates of 100 versus 56.4 % (p = 0.001) and OS rates of 94.4 versus 65.9 % (p = 0.045). Similarly, a smaller MTV (<7.2 cc) correlated with improved 2-year actuarial LC rates of 100 versus 54.2 % (p < 0.001) and OS rates of 94.7 versus 64.2 % (p = 0.04). Smaller GTV and MTV correlated with improved NC, DC, OC, and DFS, as well.ConclusionGTV and MTV demonstrate superior prognostic utility as compared to SUVmax, with larger tumor volumes correlating with inferior local control and overall survival in HNSCC patients treated with definitive IMRT.

Long-Term Results Following Postoperative Radiotherapy for Soft Tissue Sarcomas of the Extremity

To review long-term outcomes following postoperative radiotherapy (RT) for extremity soft tissue sarcoma (STS) and identify variables affecting the therapeutic ratio. Between 1970 and 2008, 173 patients with localized extremity STS were treated with postoperative radiation. No patients received prior irradiation. Sixteen percent of tumors had recurred after initial surgery alone; 89% of tumors were high grade. The median patient age was 57 years (range, 18-86 years). Sixty-one percent underwent >1 surgery before RT in an attempt to achieve wide negative margins. Final margin status was negative in 70% and marginal or microscopically positive in 30%. The median time between final surgery and start of RT was 40 days. The median RT dose was 65 Gy (range, 49-74 Gy). The median follow-up for all patients was 10.4 years and 13.2 years among survivors. At 10 years, local control (LC), cause-specific survival (CSS), and overall survival (OS) rates were 87%, 80%, and 70%, respectively, with 89% of local failures occurring within 3 years after treatment. On multivariate analysis, age >55 years (82% vs 93%, P<.05) and recurrent presentation (67% vs 91%, P<.05) were associated with inferior 10-year LC. The LC according to final margin status was 90% for wide negative margins vs 79% for marginal/microscopically positive margins (P=.08). Age>55 years and local recurrence were associated with inferior CSS and OS on multivariate analysis. Twelve percent of patients experienced grade 3+ toxicity; 12 of these occurred in patients with tumors of the proximal lower extremity, with the most common toxicity of pathologic fracture occurring in 6.3%. This large single-institution series confirms that postoperative RT for STS of the extremities provides good long-term disease control with acceptable toxicity. Our experience supports recurrent presentation and older age as adverse prognostic factors for LC.

Local tumor progression following lipiodol-based targeted chemoembolization of hepatocellular carcinoma: a retrospective comparison of miriplatin and epirubicin

PurposeWe aimed to compare the local control rates between miriplatin and epirubicin in lipiodol-based transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Patients and methodsPatients who underwent targeted TACE using miriplatin (47 patients, 66 lesions) or epirubicin (64 patients, 79 lesions) as the sole therapy were enrolled. The local control rates were compared using the Kaplan–Meier estimator with the log-rank test. The patient and tumor parameters were subjected to univariate and multivariate analyses using the Cox proportional hazards model.ResultsThe overall local recurrence rates were 39.3% and 31.6% for the miriplatin and epirubicin groups, respectively. The local control rate was significantly higher in the epirubicin group than in the miriplatin group (P < 0.001). The local control rates at 6 months and 1 year were 70.7% and 44.8% for the miriplatin group and 83.4% and 69.2% for the epirubicin group, respectively. Multivariate analysis showed that the serum α-fetoprotein level ≥ 20 ng/mL (hazard ratio 2.96; P < 0.001), miriplatin usage (hazard ratio 2.53; P = 0.002), and Child-Pugh class B (hazard ratio 1.89; P = 0.042) affected local progression.ConclusionLipiodol-based targeted TACE using miriplatin had inferior local control rates as compared to epirubicin in patients with HCC.

Clinical Investigations Impact of point A asymmetry on local control and survival for low dose-rate (LDR) brachytherapy in cervical cancer

PurposeTo evaluate whether Point A asymmetry in low dose-rate (LDR) brachytherapy is associated with local control (LC), disease-free survival (DFS) and/or overall survival (OS).Material and methodsA retrospective analysis of disease control and survival outcomes was conducted for patients who underwent LDR brachytherapy for advanced cervical cancer. Institutional protocol entailed concurrent chemotherapy and whole pelvis radiotherapy (WPRT) over 5 weeks, followed by placement of Fletcher-Suit tandem and colpostat applicators at weeks 6 and 8. Objective Point A doses, 80-85 Gy, were accomplished by placement of Cesium-137 (Cs-137) sources. Cox proportional hazards regression models were used to assess associations between disease control and survival endpoints with variables of interest.ResultsThe records of 50 patients with FIGO stage IB1-IVA cervical cancer undergoing LDR brachytherapy at our institution were identified. Thirty of these patients had asymmetry > 2.5%, and 11 patients had asymmetry > 5%. At a median survivor follow-up of 20.25 months, 15 patients had experienced disease failure (including 5 cervical/vaginal apex only failures and 2 failures encompassing the local site). Right/left dose asymmetry at Point A was associated with statistically significantly inferior LC (p = 0.035) and inferior DFS (p = 0.011) for patients with mean Point A dose of > 80 Gy. Insufficient evidence existed to conclude an association with OS.ConclusionsLDR brachytherapy may be associated with clinically significant dose asymmetry. The present study demonstrates that patients with Point A asymmetry have a higher risk of failure for DFS and LC.

The significance of size change of soft tissue sarcoma during preoperative radiotherapy

Aim To assess the significance of change in tumour size during preoperative radiotherapy in patients with soft tissue sarcoma (STS). Methods A retrospective review of 91 cases with STS was performed. Inclusion criteria were localised extremity and truncal STS with measurable disease, older than 18 years, treated with preoperative radiotherapy and wide local excision, in the period between January 1966 and December 2005. Patients with head and neck STS, or who received neoadjuvant chemotherapy were excluded. A difference in excess of 10% of the greatest tumour diameter of the pre-radiotherapy and the post-radiotherapy MRI scans was considered as change in tumour size. Results Increase in tumour size was noted in 28 patients (31%) (Group 1). No change or decrease in size was observed in 63 patients (Group 2). There were no significance differences in local control or overall survival rates between the 2 groups. The estimated overall actuarial local recurrence free, event-free and overall survival rates were 90.5%, 64.4%, 62.9% in Group 1, and 85.7%, 60.8%, 68.9% in Group 2 respectively. Conclusion Increase in tumour size during preoperative radiotherapy for soft tissue sarcoma does not seem to associate with inferior local tumour control or compromise survival. Lack of reduction in tumour size is not necessarily a sign of lack of response to preoperative radiotherapy.