Local-regional Control Research Articles

Clinical outcomes and toxicity after exclusive versus postoperative radiotherapy in supraglottic cancer: new solutions for old problems? The case of stage III and IV disease.

To compare toxicity, survival and laryngeal preservation rate after radiotherapy alone (RR), radiotherapy after supraglottic horizontal laryngectomy (SHLR) and radiotherapy after total laryngectomy (TLR) for advanced supraglottic laryngeal cancer. From 1984 to 2012, 532 patients (pts) were treated in our Department: 273 were potentially fit for conservative surgery (Group I) and 259 were not amenable to partial surgery (Group II). A younger age (p = 0.005), a better performance status (p < 0.001), the absence of comorbidities (p < 0.001) and the absence of nodal involvement (p = 0.006) favorably impacted on overall survival. More high-grade mucositis (p = 0.009), mild dysphagia (p < 0.001) and mild xerostomia (p < 0.001) were found in RR group; surgical patients had more edema of neck (p = 0.009) and skin toxicity (p = 0.008). Group I No differences in local, nodal and distant recurrences and in number of rescue laryngectomies were observed. The disease characteristics (T, N and stage) but not the treatment modality impacted on disease-free survival (DFS). Group II There was an higher number of local (p = 0.013) and nodal (p = 0.022) recurrences after RR. DFS (p = 0.01) was longer after TLR. No differences in DFS between TLR patients and RR patients who underwent radio-chemotherapy were found. In Group I, RR results in a local-regional control and organ preservation comparable to surgical treatments, with only slight increase of late mild xerostomia and dysphagia. In Group II RR was less effective than TLR, with a significantly worse DFS. The use of concurrent radical radio-chemotherapy seems to provide comparable loco-regional control to TLR.

Ipsilateral radiotherapy for squamous cell carcinoma of the tonsil

The purpose of this study is to update our institution's experience with ipsilateral radiation therapy (RT) for squamous cell carcinoma of the tonsillar area. Outcome study of 76 patients treated between 1984 and 2012 with ipsilateral RT for squamous cell carcinoma of the tonsil. Patients had either cT1 (n=41, 54%) or cT2 (n=35, 46%) primaries and cN0 (n=27, 36%), cN1 (n=15, 20%), cN2a (n=8, 11%), or cN2b (n=26, 34%) nodal disease. Of these, 32 (42%) patients underwent a planned neck dissection and 21 (28%) patients received concomitant chemotherapy. Median follow-up for all patients was 7.1years (range 0.1-27.2) and 7.8years (range 2.1-27.2years) for living patients. The 2- and 5-year control and survival rates were as follows: local control, 98.6 and 96.9%; local-regional control 95.8 and 92.6%; cause-specific survival 95.9 and 93.1%; and overall survival, 92.1 and 83.8%. One patient failed in the contralateral, non-radiated neck 3years after primary treatment. Univariate analysis revealed that overall survival was significantly influenced by whether the patient had a primary tumor in the anterior tonsillar pillar versus the tonsillar fossa with the latter performing better. The incidence of severe late complications was 16%. Ipsilateral RT for patients with squamous cell carcinoma of the anterior tonsillar pillar or tonsillar fossa with no base of tongue or soft palate extension is an efficacious treatment that provides excellent control rates with a relatively low incidence of late complications.

Evidence on effectiveness of intensity‐modulated radiotherapy versus 2‐dimensional radiotherapy in the treatment of nasopharyngeal carcinoma: Meta‐analysis and a systematic review of the literature

Current management of nasopharyngeal carcinoma (NPC) uses radiotherapy (RT) as the curative treatment modality. Radiation delivery techniques for NPC can be achieved using 2D conventional RT or intensity-modulated radiotherapy (IMRT). A systematic review and meta-analysis of the literature was undertaken to assess the effectiveness of IMRT versus 2D conventional RT in primary treatment of NPC. IMRT showed better results than 2D conventional RT in terms of local control, regional control, and overall survival, but when stratified, only in T4, N2, and stage III were the differences that were seen. Objective saliva measurements and physician-graded xerostomia were better in IMRT. However, patient-reported xerostomia showed minimal improvement only in IMRT. The evidence of superiority of IMRT over 2D conventional RT is not clear. In the absence of more clinical data demonstrating the superiority of IMRT in the treatment of nasopharyngeal carcinoma, 2D conventional RT seems to be a reasonable treatment option, especially in limited resource settings. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2130-E2142, 2016.

Primary radiotherapy for squamous cell carcinoma of the pyriform sinus

The objective of this study is to report the long-term outcomes of primary radiotherapy (RT) for patients with T1-T2 squamous cell carcinomas (SCC) of the pyriform sinus. Between November 1964 and March 2008, 135 patients with T1-T2 pyriform sinus SCC were treated with primary RT at the University of Florida. Adjuvant chemotherapy was employed in 21 patients (16%) and 62 patients (46%) underwent a planned neck dissection. Median follow-up was 3.5years (range 0.2-24.7years); median follow-up on living patients was 8.3years (range 3.8-24.0years). The 5-year outcomes were as follows: local control, 85%; regional control, 81%; local-regional control, 71%; distant metastasis-free survival, 76%; cause-specific survival, 62%; and overall survival, 38%. The 5-year local control rate was 88% for T1 cancers and 84% for those with T2 SCCs (p=0.5429). Sixteen patients (12%) experienced severe late complications. Primary RT results in a high probability of cure with a relatively modest risk of severe late complications for patients with T1-T2 SCCs of the pyriform sinus.

Impact of Radiographic Findings on For Prognosis Skin Cancer With Perineural Invasion

Update our experience using radiotherapy (RT) for head-and-neck squamous or basal cell carcinoma with clinical perineural invasion (PNI) and correlate radiographic findings with outcomes. We treated 65 patients with cT4N0 head-and-neck skin cancers with clinical PNI from 1965 to 2009 (N0 disease, 59; N1 disease, 6). Treatment included RT alone (N=18), RT with concurrent chemotherapy (N=14), surgery and postoperative RT (N=26), or postoperative RT with concurrent chemotherapy (N=5), and preoperative RT and surgery (N=2). Patients were stratified by imaging-negative disease (N=11), minimal or moderate peripheral disease (N=18), and macroscopic and/or central disease (N=36). Median RT dose was 72.6 Gy (50.4 to 79.2 Gy). Median follow-up overall and for living patients was 5.4 and 11.6 years, respectively. Five-year outcomes for imaging-negative disease versus minimal/moderate peripheral disease versus macroscopic/central disease were: local control, 81% versus 60% versus 47% (P=0.23); local-regional control, 80% versus 54% versus 47% (P=0.22); neck control, 100% versus 89% versus 93% (P=0.45); and distant metastasis-free survival, 89% versus 100% versus 93% (P=0.57), respectively. Five-year survival rates for imaging-negative disease versus minimal/moderate peripheral disease versus macroscopic/central disease were: overall survival, 82% versus 50% versus 52% (P=0.26), and cause-specific survival, 100% versus 58% versus 65% (P=0.08). Twenty-two (34%) patients had 1 or more severe (grade ≥3) late complications. There is a nonsignificant trend towards improved local control for imaging-negative patients and patients with minimal/moderate peripheral disease compared with macroscopic/central disease. Although survival appears better for imaging-negative patients, extent of imaging-positive PNI did not impact overall or cause-specific survival.

Early clinical outcomes of ultrasound-guided CT-planned high-dose-rate interstitial brachytherapy for primary locally advanced cervical cancer.

To report early clinical outcomes of high-dose-rate interstitial image-guided brachytherapy (BT) in the definitive management of locally advanced cervical cancer. We retrospectively analyzed 31 locally advanced cervical cancer patients treated at our institution between January 2010 and April 2013. About 88% had advanced disease based on the International Federation of Gynecology and Obstetrics guidelines, and 87% received concurrent chemotherapy. All patients were treated with external beam radiation therapy to a median dose of 45Gy (range, 39.6-58Gy) before receiving BT. High-dose-rate BT was delivered in a single implant to a median dose of 6Gy × five fractions to a CT-defined volume. Median total equivalent 2-Gy dose, dose covered by 90% of the high-risk clinical target volume (HR-CTV D90), and HR-CTV were 84, 87.4, and 49.9 cc, respectively. Kaplan-Meier method was used for actuarial survival analysis, and toxicity was graded using Common Terminology Criteria for Adverse Events, version 4.0. Median followup was 19.3months. Two-year actuarial local control, regional control, and distant metastasis (DM) were 90%, 93%, and 23.6%, respectively. Two-year disease-free survival was 55%. Genitourinary, gastrointestinal, or gynecologic Grade 3 toxicity was seen in 5 patients (3 T4a and 2 T3b) for crude rates of 13%, 7%, and 3%, respectively. Stratifying HR-CTV by <30 and >30 cc and then by HR-CTV D90 of <85, 85-90, and >90Gy showed that 100% of the local failures, regional failures, DM, and G3 toxicity occurred in >30 cc group. The rate of DM was also significantly higher in the >30 cc group (p=0.036). An interstitial approach can achieve excellent outcomes in cases where intracavitary and/or hybrid approaches are either not suitable or not available.

Adjuvant intensity-modulated radiotherapy (IMRT) with concurrent paclitaxel and cisplatin in cervical cancer patients with high risk factors: A phase II trial

ObjectiveTo evaluate the safety and efficacy of adjuvant intensity-modulated radiotherapy (IMRT) with concurrent paclitaxel and cisplatin (TP) in early stage cervical cancer patients with high risk factors after radical hysterectomy. MethodsPatients who underwent radical hysterectomy for FIGO stage IB–IIA cervical cancer and had high risk factors for recurrence were recruited. One cycle of TP was delivered before and after concurrent chemoradiotherapy, respectively. Concurrent chemoradiotherapy began 21 days after the start of the initial cycle of the chemotherapy with two cycles of TP delivered on day 1 and day 29 of radiotherapy. Primary endpoints were overall survival (OS) and relapse-free survival (RFS), with toxicities, local-regional control (LC) and distant failure (DF) rate as secondary endpoints. ResultsBetween 2008 and 2012, 67 patients were evaluable. The 2 and 4-year RFS rates were 98.2% and 92.9%. Corresponding OS rates were 100%, and 98.0%, respectively. The 4-year LC and DF rates were 98.0% and 5.2%, respectively. Grade 3–4 acute leucopenia, neutropenia and thrombocytopenia occurred in 25.4%, 11.9% and 1.5% of patients, respectively. There were 89.6% and 59.7% patients experienced acute vomiting and diarrhea, but only 6.0% and 6.0% patients were grade 3, respectively. No case of chronic toxicity exceeded grade 2. ConclusionAdjuvant concurrent IMRT with paclitaxel plus cisplatin are safe and effective in early stage cervical cancer patients with high risk factors for recurrence following radical hysterectomy.

Abstract P1-15-25: Phase II trial of hypofractionated post mastectomy radiation

Abstract Purpose: The efficacy of irradiating the chest wall and draining lymph nodes after mastectomy in improving local regional control has been firmly established by multiple trials comparing mastectomy alone to mastectomy with postoperative radiation. The currently accepted standard of care involves 25 fractions of chest wall and nodal radiation plus an optional 5 fraction scar boost. Given recent publications with intact breast radiation demonstrating equivalence with shorter course radiation treatment, we sought to establish a short course of radiation for women post mastectomy that would be equivalent to conventional radiation in terms of local control and complications. Methods: Starting in 2011, Stage II and III, unilateral breast cancer patients were prospectively consented to participate in our study at Rutgers Cancer Institute of New Jersey and the University of Utah. We designed a phase II non-inferiority trial, with plans to enroll 65 patients, allowing for a 18% loco-regional recurrence rate if the true rate is 10%. Patients were allowed to receive chemotherapy before or after adjuvant radiation with radiation starting 14-63 days after surgery or adjuvant chemotherapy. Patients underwent 3D simulation and were treated with ≥ 6MV photon radiation using 3D conformal tangents or intensity modulation. Regional nodal radiation was included when clinically appropriate with inclusion of internal mammary nodes at the treating provider’s discretion. The prescription dose was prescribed at 333cGy per day to the chest wall and regional nodes for 11 daily fractions followed by a recommend scar boost of 333cGy per day for 4 fractions. Chest wall PTV was keep within 90-115% of the prescribed dose, the maximum brachial plexus dose was keep below 3919cGy (107%) and no portion of the heart could receive &amp;gt;2Gy/day. The maximum dose of the boost field was kept to 120% of the boost prescription. Any breast reconstruction technique was allowed, per institutional standard. Results: 48 patients have thus far been enrolled with a median follow up interval of 17 months. Looking at the 43 patients with &amp;gt; 4 months of follow-up, we have only seen a 4.7% grade 3 or greater acute or late toxicity rate, with one grade 3 wound complications, and one grade 3 fibrosis. There has been one chest wall recurrence, for a 2.3% local recurrence rate. Conclusion: Early results would appear to show that hypofractionated post mastectomy radiation appears to be safe and feasible. Acute toxicity is less than anticipated, however it is too early make any conclusions on efficacy or late effects, with only 48 out of 65 patients enrolled. We hope to use the results of this phase II trial to design a randomized prospective trial comparing hypofractionated post mastectomy radiation to standard fraction. Citation Format: Matthew M Poppe, Bruce G Haffty, Atif J Khan. Phase II trial of hypofractionated post mastectomy radiation [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 P1-15-25.

Re-irradiation in lung cancer

Local-regional control is an important component of care for patients treated for lung cancer. Local-regional disease progression can lead directly to problems including pain, dysphagia, hemoptysis, cough, dyspnea, superior vena cava syndrome, and death. Local-regional failure remains common despite advances in radiation therapy, chemotherapy, and surgery. For patients and caregivers, local-regional failure management poses a dilemma for balancing safety and efficacy. Multiple strategies for local-regional failure management exist. This report examines data from the use of external beam radiation therapy, stereotactic body radiotherapy, and endobronchial brachytherapy for management of local-regional failure in lung cancer.

Radiation therapy for nasal vestibule squamous cell carcinoma: a 40-year experience.

We evaluated the treatment of squamous cell carcinoma (SCC) of the nasal vestibule. Eighty-six patients were treated with radiotherapy (RT) and 13 patients received surgery and RT. The mean follow-up was: 9.7 years (range 4 months-35.9 years). The 5- and 10-year outcomes were: local control (LC), 88 and 82 %; local-regional control (LRC), 78 and 73 %; freedom from distant metastases (FFDM), 96 and 96 %; cause-specific survival (CSS), 91 and 86 %; and overall survival, 75 and 51 %. The 5- and 10-year LC rates for patients treated with RT were 94 and 89 % overall. A multivariate analysis was performed. Tumor size predicted LC, LRC, OS, and CSS. Overall stage predicted LRC. RT cures most patients with T1-T2 and favorable T4 SCCs with acceptable toxicity. RT and surgery result in improved likelihood of cure for patients with advanced T4 lesions.

P291 Influence of radiation boost on local control in patients with ductal carcinoma in situ

Goals: The aim of this study is to evaluate the role of postmastectomy radiotherapy (PMRT) in clinical stage II and III breast cancer patients who achieved negative node status (pN0) after neoadjuvant chemotherapy (NAC). Methods:We retrospectively analyzed the outcomes of 143 patients with pN0 after NAC and mastectomy at Fudan University Shanghai Cancer Center. In total, 103 (72%) patients received PMRT, and 40 (28%) patients did not. Univariate and multivariate survival analyses were performed to evaluate the effect of PMRT on locoregional recurrence-free survival (LRRFS) and overall survival (OS) of the two groups. Results: There were no differences between the two groups with respect to age, nuclear grade, estrogen receptor (ER) status, HER2/neu receptor status, lymphovascular space invasion (LVSI) status or pathological tumor size. However, a significantly higher proportion of patients in the irradiated group (64%) had clinical lymph node involvement than in the nonirradiated group (45%). After a median follow-up time of 49 months, 10 locoregional recurrence events occurred. For the entire cohort of patients, use of radiation therapy improved the 5-year LRRFS rate (94.5% vs. 80.2%; P = 0.032) but not the 5-year OS rate (92.2% vs. 88.7%; P = 0.617). In the subset of patients who presented with clinically stage II disease, the 5-year LRRFS and 5-year OS did not differ significantly between the PMRT and no-PMRT group (96.3% vs. 91.3%; P = 0.190 and 96.2% vs. 91.3%; P = 0.199, respectively). For patientswith stage III disease at diagnosis, a trend was seen toward better local regional control with PMRT (the 5-year LRRFS rate was 92.7% vs. 64.2%; P = 0.063), although the benefit from radiation with respect to OS was not significant (5-year OS rate was 88.1% vs. 85.2%; P = 0.657). On multivariate Cox regression analyses, the clinical tumor size (hazard ratio [HR], 3.27; 95% confidence interval [CI], 1.05–10.18; P = 0.041), pathologic breast tumor response (HR, 1.82; 95%CI, 1.11– 3.77; P = 0.046) and delivery of radiation therapy (HR, 1.27; 95%CI, 1.08–9.25; P = 0.047) were independent predictors of locoregional recurrence. Conclusion: For patientswho achieved pN0 after NAC, PMRT seemed to provide a clinical benefit for breast cancer patients with stage III disease. Omission of PMRT in patients with stage II disease did not increase the risk of locoregional recurrence and death. Disclosure of Interest: No significant relationships.

Double regularization control based on level set evolution for tablet packaging image segmentation

This paper proposes a novel double regularization control (DRC) method which is used for tablet packaging image segmentation. Since the intensities of tablet packaging images are inhomogenous, it is difficult to make image segmentation. Compared to methods based on level set, the proposed DRC method has some advantages for tablet packaging image segmentation. The local regional control term and the rectangle initialization contour are first employed in this method to quickly segment uneven grayscale images and accelerate the curve evolution rate. Gaussian filter operator and the convolution calculation are then adopted to remove the effects of texture noises in image segmentation. The developed penalty energy function, as regularization term, increases the constrained conditions based on the gradient flow conditions. Since the potential function is embedded into the level set of evolution equations and the image contour evolutions are bilaterally extended, the proposed method further improves the accuracy of image contours. Experimental studies show that the DRC method greatly improves the computational efficiency and numerical accuracy, and achieves better results for image contour segmentation compared to other level set methods.

The relationship between human papillomavirus and prognosis of oropharyngeal squamous cell carcinoma: a meta analysis

OBJECTIVE To examine survival differences in prognosis and survival between patients with HPV-positive and those with HPV-negative oropharyngeal squamous cell carcinoma (OPSCC). Pubmed, Embase, Web of science and Medline databases were searched from their inception till June 2014. A random-effect meta-analysis was used to pool study estimates evaluating overall (all-cause mortality), disease-specific (death from OPSCC), disease-free (recurrence free), progression-free survival outcomes and local regional control rate in HPV-positive vs HPV-negative OPSCC. After study selection, two reviewers assessed and extracted data independently. Meta-analysis was performed using the STATA 11.0 software. Thirty-seven studies were included. HPV-positive OPSCC patients had a better overall survival compared to HPV-negative patients (HR 0.39, 95% CI 0.32-0.46). HPV-positive OPSCC patients had a significantly lower disease specific mortality (HR 0.31, 95% CI 0.22-0.39) and were less likely to experience progression or recurrence of their cancers than HPV-negative patients (HR 0.34, 95% CI 0.25-0.42). Both disease-free survival and progression-free survival were significantly improved in patients with HPV-positive OPSCC ( HR 0.38, 95% CI 0.29-0.47 and HR 0.46, 95% CI 0.29-0.63, respectively). HPV infection is an important prognostic factor of OPSCC. Stratified therapies can be applied in OPSCC based on HPV status of tumours.

Metabolic Tumor Volume as a Prognostic Imaging-Based Biomarker for Head-and-Neck Cancer: Pilot Results From Radiation Therapy Oncology Group Protocol 0522

To evaluate candidate fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging biomarkers for head-and-neck chemoradiotherapy outcomes in the cooperative group trial setting. Radiation Therapy Oncology Group (RTOG) protocol 0522 patients consenting to a secondary FDG-PET/CT substudy were serially imaged at baseline and 8 weeks after radiation. Maximum standardized uptake value (SUVmax), SUV peak (mean SUV within a 1-cm sphere centered on SUVmax), and metabolic tumor volume (MTV) using 40% of SUVmax as threshold were obtained from primary tumor and involved nodes. Of 940 patients entered onto RTOG 0522, 74 were analyzable for this substudy. Neither high baseline SUVmax nor SUVpeak from primary or nodal disease were associated with poor treatment outcomes. However, primary tumor MTV above the cohort median was associated with worse local-regional control (hazard ratio 4.01, 95% confidence interval 1.28-12.52, P=.02) and progression-free survival (hazard ratio 2.34, 95% confidence interval 1.02-5.37, P=.05). Although MTV and T stage seemed to correlate (mean MTV 6.4, 13.2, and 26.8 for T2, T3, and T4 tumors, respectively), MTV remained a strong independent prognostic factor for progression-free survival in bivariate analysis that included T stage. Primary MTV remained prognostic in p16-associated oropharyngeal cancer cases, although sample size was limited. High baseline primary tumor MTV was associated with worse treatment outcomes in this limited patient subset of RTOG 0522. Additional confirmatory work will be required to validate primary tumor MTV as a prognostic imaging biomarker for patient stratification in future trials.

Long-Term Results of Radiation Therapy Oncology Group 9903: A Randomized Phase 3 Trial to Assess the Effect of Erythropoietin on Local-Regional Control in Anemic Patients Treated With Radiation Therapy for Squamous Cell Carcinoma of the Head and Neck

This paper reports long-term results of RTOG 9903,to determine whether the addition of erythropoietin (EPO) would improve the outcomes of radiation therapy (RT) in mildly to moderately anemic patients with head and neck squamous cell carcinoma (HNSCCa). The trial included HNSCCa patients treated with definitive RT. Patients with stage III or IV disease received concomitant chemoradiation therapy or accelerated fractionation. Pretreatment hemoglobin levels were required to be between 9.0 and 13.5g/dL (12.5g/dL for females). EPO, 40,000 U, was administered weekly starting 7 to 10days before RT was initiated in the RT+EPO arm. A total of 141 of 148 enrolled patients were evaluable. The baseline median hemoglobin level was 12.1g/dL. In the RT+EPO arm, the mean hemoglobin level at 4weeks increased by 1.66g/dL, whereas it decreased by 0.24g/dL in the RT arm. With a median follow-up of 7.95years (range: 1.66-10.08years) for surviving patients and 3.33years for all patients (range: 0.03-10.08years), the 5-year estimate of local-regional failure was 46.2% versus 39.4% (P=.42), local-regional progression-free survival was 31.5% versus 37.6% (P=.20), and overall survival was 36.9% versus 38.2% (P=.54) for the RT+EPO and RT arms, respectively. Late toxicity was not different between the 2 arms. This long-term analysis confirmed that despite the ability of EPO to raise hemoglobin levels in anemic patients with HNSCCa, it did not improve outcomes when added to RT. The possibility of a detrimental effect of EPO could not be ruled out.

Radiation Therapy for Mucosal Melanoma of the Head and Neck

The aim of this study was to evaluate the long-term effectiveness and complications of radiotherapy (RT) in the treatment of patients with mucosal melanomas of the head and neck. The medical records of 21 patients treated with definitive or postoperative (RT) between 1974 and 2011 at the University of Florida Department of Radiation Oncology in Gainesville, FL, and the University of Florida Proton Therapy Institute in Jacksonville, FL, were retrospectively reviewed under an Institutional Review Board-approved protocol. Primary sites included nasal cavity, oropharynx, and paranasal sinuses. Sixteen patients (76%) received surgery and postoperative RT and 5 patients (24%) received RT alone. Seventeen patients received photon RT alone, whereas 4 patients received combined photon-based and proton-based RT. Median follow-up for all patients was 1.05 years (range, 0.36 to 12.97 y); median follow-up for survivors was 2.2 years (range 0.9 to 13.0 y). The 5-year outcomes were: local control, 79%; regional control, 85%; local-regional control, 65%; distant metastasis-free survival, 20%; cause-specific survival, 22%; and overall survival, 22%. Three patients (14%) experienced severe complications including bilateral blindness and skin necrosis. Definitive or postoperative RT for mucosal melanoma of the head and neck yields fairly good local-regional control of disease. The prognosis for patients treated with definitive RT is less promising than for those who receive surgery and postoperative RT.

Local-Regional Treatment of the Patient With Inflammatory Breast Cancer

Inflammatory breast cancer (IBC) is a diagnosis based on a constellation of clinical features including a rapid onset of breast erythema and edema (peau d’orange) of a third or more of the skin of the breast and with a palpable border to the edema. Incidence has increased although it makes up only 1–4 % of all breast cancer diagnoses. In spite of some encouraging recent clinical outcome data, published local-regional control rates are consistently lower than expected in non-IBC and are of particular concern in this disease that readily progresses locally to carcinoma en cuirasse. With a focus on radiotherapy, this review provides a critical evaluation of the recent literature evaluating local-regional treatment of IBC, highlights new findings in the local-regional management of IBC, and offers an introduction to future directions regarding the optimal treatment and management of IBC.

Panitumumab plus radiotherapy versus chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-2): a randomised, controlled, open-label phase 2 trial

We aimed to compare panitumumab, a fully human monoclonal antibody against EGFR, plus radiotherapy with chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck. In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 22 sites in eight countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥ 10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (two cycles of cisplatin 100 mg/m(2) during radiotherapy) or to radiotherapy plus panitumumab (three cycles of panitumumab 9 mg/kg every 3 weeks administered with radiotherapy) using a stratified randomisation with a block size of five. All patients received 70-72 Gy to gross tumour and 54 Gy to areas of subclinical disease with accelerated fractionation radiotherapy. The primary endpoint was local-regional control at 2 years, analysed in all randomly assigned patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This study is registered with ClinicalTrials.gov, number NCT00547157. Between Nov 30, 2007, and Nov 16, 2009, 152 patients were enrolled, and 151 received treatment (61 in the chemoradiotherapy group and 90 in the radiotherapy plus panitumumab group). Local-regional control at 2 years was 61% (95% CI 47-72) in the chemoradiotherapy group and 51% (40-62) in the radiotherapy plus panitumumab group. The most frequent grade 3-4 adverse events were mucosal inflammation (25 [40%] of 62 patients in the chemoradiotherapy group vs 37 [42%] of 89 patients in the radiotherapy plus panitumumab group), dysphagia (20 [32%] vs 36 [40%]), and radiation skin injury (seven [11%] vs 21 [24%]). Serious adverse events were reported in 25 (40%) of 62 patients in the chemoradiotherapy group and in 30 (34%) of 89 patients in the radiotherapy plus panitumumab group. Panitumumab cannot replace cisplatin in the combined treatment with radiotherapy for unresected stage III-IVb squamous-cell carcinoma of the head and neck, and the role of EGFR inhibition in locally advanced squamous-cell carcinoma of the head and neck needs to be reassessed. Amgen.

Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1): a randomised, controlled, open-label phase 2 trial

Panitumumab is a fully human monoclonal antibody that targets EGFR. We aimed to compare chemoradiotherapy plus panitumumab with chemoradiotherapy alone in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck. In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 41 sites in nine countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥ 10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (three cycles of cisplatin 100 mg/m(2)) or panitumumab plus chemoradiotherapy (three cycles of intravenous panitumumab 9.0 mg/kg every 3 weeks plus cisplatin 75 mg/m(2)) using stratified randomisation with a block size of five. All patients received 70 Gy to gross tumour and 50 Gy to areas at risk for subclinical disease with standard fractionation. The primary endpoint was local-regional control at 2 years, analysed in all randomised patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00500760. Between Oct 26, 2007, and March 26, 2009, 153 patients were enrolled and 150 received treatment (63 in the chemoradiotherapy group and 87 in the panitumumab plus chemoradiotherapy group). Local-regional control at 2 years was 68% (95% CI 54-78) in the chemoradiotherapy group and 61% (50-71) in the panitumumab plus chemoradiotherapy group. The most frequent grade 3-4 adverse events were dysphagia (17 [27%] of 63 patients in the chemoradiotherapy group vs 35 [40%] of 87 in the panitumumab plus chemoradiotherapy group), mucosal inflammation (15 [24%] vs 48 [55%]), and radiation skin injury (eight [13%] vs 27 [31%]). Serious adverse events were reported in 20 (32%) of 63 patients in the chemoradiotherapy group and in 37 (43%) of 87 patients in the panitumumab plus chemoradiotherapy group. In patients with locally advanced squamous-cell carcinoma of the head and neck, the addition of panitumumab to standard fractionation radiotherapy and cisplatin did not confer any benefit, and the role of EGFR inhibition in these patients needs to be reassessed. Amgen.

Concurrent cisplatin-based chemotherapy versus radiotherapy alone as adjuvant therapy for squamous cell carcinoma of the oral cavity bearing high-risk features

Background: To compare concurrent cisplatin-based chemoradiation in an adjuvant setting for high-risk squamous cell carcinoma of oral cavity terms of toxicity, local-regional control, and overall survival. Materials and Methods: A total of 54 patients of postoperative squamous cell carcinoma of oral cavity with high-risk features were randomized into two groups; postoperative radiation (60 Gy/30#/6 weeks) or postoperative concurrent chemoradiation (60 Gy/30#/6 weeks with weekly concurrent cisplatin 50 mg) arms. Results: Buccal mucosa was the most common sub site (44.4%) affected, followed by lower alveolus/alveolar ridge (37%) and most tumors (64.3%) were well-differentiated. About 67.3% of the patients completed their course of radiation within 6 weeks with only 69 patients receiving the scheduled 60 Gy of external beam radiation therapy dose. Only 6 patients out of 22 completed the 6 cycles of weekly chemotherapy with compliance decreasing most after 3 cycles. Mucositis and dysphagia were significantly higher in the chemoradiation arm. After a median follow-up of 47 months, the loco-regional control rate was 51.4% in the postoperative chemoradiation arm as compared to 35.56% in the postoperative radiation arm. The 5 years overall survival was 56.4% in postoperative chemoradiation arm as compared to 51.3% in the postoperative radiation only. Conclusion: Postoperative concurrent chemoradiation with weekly cisplatin in high-risk oral cancer gave an advantage in the loco-regional control rate and overall survival at the end of 47 months, with significant increase in acute toxicities Grade III and Grade IV toxicities.