The epidermal growth factor receptor (EGFR) in head and neck cancer: its role and treatment implications

Epidermal growth factor receptor (EGFR) is a member of the ErbB family of receptors. Its stimulation by endogenous ligands, EGF or transforming growth factor-alpha (TGF-α) results in activation of intracellular tyrosine kinase, therefore, cell cycle progression. High levels of EGFR expression are correlated with poor prognosis and resistance to radiation therapy in a variety of cancers, mostly in squamous-cell carcinoma of the head and neck (SCCHN). Blocking the EGFR by a monoclonal antibody results in inhibition of the stimulation of the receptor, therefore, in inhibition of cell proliferation, enhanced apoptosis, and reduced angiogenesis, invasiveness and metastases. The EGFR is a prime target for new anticancer therapy in SCCHN, and other agents in development include small molecular tyrosine kinase inhibitors and antisense therapies

Different meaning of the mean heart dose between 3D-CRT and IMRT for breast cancer radiotherapy

BackgroundPrevious studies in 2D and in 3D conformal radiotherapy concludes that the maximal heart distance and the mean heart dose (MHD) are considered predictive of late cardiac toxicities. As the use of inverse-planned intensity modulated radiation therapy (IMRT) is increasing worldwide, we hypothesized that this 3D MHD might not be representative of heart exposure after IMRT for breast cancer (BC).MethodsPatients with left-sided BC and unfavorable cardiac anatomy received IMRT. Their treatment plan was compared to a virtual treatment plan for 3D conformal radiotherapy with similar target volume coverage (study A). Then, a second 3D conformal treatment plan was generated to achieve equivalent individual MHD obtained by IMRT. Then the heart and left anterior descending (LAD) coronary artery exposures were analyzed (study B). Last, the relationship between MHD and the heart volume or LAD coronary artery volume receiving at least 30Gy, 40Gy and 45Gy in function of each additional 1Gy to the MHD was assessed (study C).ResultsA significant decrease of heart and LAD coronary artery exposure to high dose was observed with the IMRT compared with the 3D conformal radiotherapy plans that both ensured adequate target coverage (study A). The results of study B and C showed that 3D MHD was not representative of similar heart substructure exposure with IMRT, especially in the case of high dose exposure.ConclusionsThe mean heart dose is not a representative dosimetric parameter to assess heart exposure following IMRT. Equivalent MHD values following IMRT and 3DRT BC treatment do not represent the same dose distribution leading to extreme caution when using this parameter for IMRT plan validation

Bilateral kidney preservation by volumetric-modulated arc therapy (RapidArc) compared to conventional radiation therapy (3D-CRT) in pancreatic and bile duct malignancies

<p>Abstract</p> <p>Background</p> <p>To compare volumetric-modulated arc therapy plans with conventional radiation therapy (3D-CRT) plans in pancreatic and bile duct cancers, especially for bilateral kidney preservation.</p> <p>Methods</p> <p>A dosimetric analysis was performed in 21 patients who had undergone radiotherapy for pancreatic or bile duct carcinoma at our institution. We compared 4-field 3D-CRT and 2 arcs RapidArc (RA) plans. The treatment plan was designed to deliver a dose of 50.4 Gy to the planning target volume (PTV) based on the gross disease in a 1.8 Gy daily fraction, 5 days a week. Planning objectives were 95% of the PTV receiving 95% of the prescribed dose and no more than 2% of the PTV receiving more than 107%. Dose-volume histograms (DVH) for the target volume and the organs at risk (right and left kidneys, bowel tract, liver and healthy tissue) were compared. Monitor units and delivery treatment time were also reported.</p> <p>Results</p> <p>All plans achieved objectives, with 95% of the PTV receiving ≥ 95% of the dose (D95% for 3D-CRT = 48.9 Gy and for RA = 48.6 Gy). RapidArc was shown to be superior to 3D-CRT in terms of organ at risk sparing except for contralateral kidney: for bowel tract, the mean dose was reduced by RA compared to 3D-CRT (16.7 vs 20.8 Gy, p = 0.0001). Similar result was observed for homolateral kidney (mean dose of 4.7 Gy for RA vs 12.6 Gy for 3D-CRT, p < 0.0001), but 3D-CRT significantly reduced controlateral kidney dose with a mean dose of 1.8 Gy vs 3.9 Gy, p < 0.0007. Compared to 3D-CRT, mean MUs for each fraction was significantly increased with RapidArc: 207 vs 589, (p < 0.0001) but the treatment time was not significantly different (2 and 2.66 minutes, p = ns).</p> <p>Conclusion</p> <p>RapidArc allows significant dose reduction, in particular for homolateral kidney and bowel, while maintaining target coverage. This would have a promising impact on reducing toxicities.</p

Plan comparison of volumetric-modulated arc therapy (RapidArc) and conventional intensity-modulated radiation therapy (IMRT) in anal canal cancer

<p>Abstract</p> <p>Background</p> <p>To compare volumetric-modulated arc therapy (RapidArc) plans with conventional intensity-modulated radiation therapy (IMRT) plans in anal canal cancers.</p> <p>Methods</p> <p>Ten patients with anal canal carcinoma previously treated with IMRT in our institution were selected for this study. For each patient, three plans were generated with the planning CT scan: one using a fixed beam IMRT, and two plans using the RapidArc technique: a single (RA1) and a double (RA2) modulated arc therapy. The treatment plan was designed to deliver in one process with simultaneous integrated boost (SIB) a dose of 59.4 Gy to the planning target volume (PTV2) based on the gross disease in a 1.8 Gy-daily fraction, 5 days a week. At the same time, the subclinical disease (PTV1) was planned to receive 49.5 Gy in a 1.5 Gy-daily fraction. Plans were normalized to 99% of the PTV2 that received 95% of the prescribed dose. Planning objectives were 95% of the PTV1 will receive 95% of the prescribed dose and no more than 2% of the PTV will receive more than 107%. Dose-volume histograms (DVH) for the target volume and the organs at risk (bowel tract, bladder, iliac crests, femoral heads, genitalia/perineum, and healthy tissue) were compared for these different techniques. Monitor units (MU) and delivery treatment time were also reported.</p> <p>Results</p> <p>All plans achieved fulfilled objectives. Both IMRT and RA2 resulted in superior coverage of PTV than RA1 that was slightly inferior for conformity and homogeneity (p < 0.05).</p> <p>Conformity index (CI_95%) for the PTV2 was 1.15 ± 0.15 (RA2), 1.28 ± 0.22 (IMRT), and 1.79 ± 0.5 (RA1). Homogeneity (D_5%- D_95%) for PTV2 was 3.21 ± 1.16 Gy (RA2), 2.98 ± 0.7 Gy (IMRT), and 4.3 ± 1.3 Gy (RA1). RapidArc showed to be superior to IMRT in terms of organ at risk sparing. For bowel tract, the mean dose was reduced of 4 Gy by RA2 compared to IMRT. Similar trends were observed for bladder, femoral heads, and genitalia. The DVH of iliac crests and healthy tissue resulted in comparable sparing for the low doses (V10 and V20). Compared to IMRT, mean MUs for each fraction was significantly reduced with RapidArc (p = 0.0002) and the treatment time was reduced by a 6-fold extent.</p> <p>Conclusion</p> <p>For patients suffering from anal canal cancer, RapidArc with 2 arcs was able to deliver equivalent treatment plan to IMRT in terms of PTV coverage. It provided a better organ at risk sparing and significant reductions of MU and treatment time per fraction.</p

IMRT for locally advanced anal cancer: clinical experience of the Montpellier Cancer Center

<p>Abstract</p> <p>Purpose</p> <p>To assess outcomes of patients with carcinoma of the anal canal (CAC) treated with intensity-modulated radiation therapy (IMRT).</p> <p>Method and materials</p> <p>From August 2007 to January 2011, seventy-two patients suffering from CAC were treated with IMRT. Concurrent chemotherapy was added in case of locally advanced tumors. Radiation course consisted in delivering an initial plan to the PTV1 defined as the primary tumor and the risk area including pelvic and inguinal nodes. Forty-five Gy in daily 1.8 Gy-daily fractions were delivered five days a week. A second plan of 14.4-20 Gy to the primary tumor (PTV2) was administered in 1.8-2 Gy-daily fractions, 5 days a week. We present here the results of dosimetry, toxicities, and clinical outcome of the first 39 patients with a median follow-up of 24 months.</p> <p>Results</p> <p>Thirty-one women and eight men were included in the present analysis. Tumors were classified as stages I, II, III and IV in 2, 7, 27 and 2 patients, respectively. Median age was 59 years (range, 38-85). Radiotherapy alone (RT) or combined with chemotherapy (RCT) were delivered in 6 (15%) and 33 (85%) patients, respectively.</p> <p>Six patients (15%) required a treatment break ≥ 3 days, and median time for treatment break was 8 days (range, 3-14 days). Acute grade 3 gastrointestinal (GI) and genitourinary (GU) toxicities were seen in 10 and 5% of patients, respectively. Grade 4 toxicity was only hematologic and occurred in 12% patients receiving RCT. With a median follow-up of 24 months, no patient experienced any late grade 4 toxicity. The 2-year overall survival rate was 89%, the 2-year local relapse free survival was 77% and the 2-year colostomy-free survival rate was 85%.</p> <p>Conclusion</p> <p>IMRT is well tolerated with acceptable treatment interruption allowing dose escalation.</p

Neoadjuvant Docetaxel-Based Chemoradiation for Resectable Adenocarcinoma of the Pancreas

International audienceTo assess the safety and efficacy of a new neoadjuvant chemoradiation (CRT) docetaxel-based regimen in patients with resectable adenocarcinoma of the pancreatic head or body

Decrease in Hemoglobin Levels Following Surgery Influences the Outcome in Head and Neck Cancer Patients Treated with Accelerated Postoperative Radiotherapy

Aim: To assess the influence of hemoglobin (Hb) levels in locally advanced head and neck cancer (LAHNC) patients treated with surgery and postoperative radiotherapy (PORT). Material and Methods: Pre- and postoperative Hb levels were collected in 79 patients treated with surgery followed by accelerated PORT for LAHNC. Median follow-up was 52months (range 12-95months). Results and Discussion: Four-year overall survival (OS) rate was 51%. Neither pre- nor postoperative Hb level (<120 or 130g/l in women or men, respectively) influenced the outcome. However, when Hb decrease between pre- and postoperative Hb values was taken into account, 4-year OS was significantly higher in patients with Hb difference less than 38g/l (quartile value) compared with those with Hb decrease 38g/l or more (61% versus 16%, P=0.008). Conclusion: Decrease in Hb level by more than 38g/l after surgery secondary to blood loss influences the outcome when postoperative RT is indicate

Letrozole sensitizes breast cancer cells to ionizing radiation

INTRODUCTION: Radiotherapy (RT) is considered a standard treatment option after surgery for breast cancer. Letrozole, an aromatase inhibitor, is being evaluated in the adjuvant setting. We determined the effects of the combination of RT and letrozole in the aromatase-expressing breast tumour cell line MCF-7CA, stably transfected with the CYP19 gene. METHODS: Irradiations were performed using a cobalt-60 source with doses ranging from 0 to 4 Gy. Cells were incubated with androstenedione in the presence or absence of letrozole. Effects of treatment were evaluated using clonogenic assays, tetrazolium salt colorimetric (MTT) assays, and cell number determinations. Cell-cycle analyses were conducted using flow cytometry. RESULTS: The survival fraction at 2 Gy was 0.66 for RT alone and was 0.44 for RT plus letrozole (P = 0.02). Growth of MCF-7CA cells as measured by the cell number 6 days after radiotherapy (2 and 4 Gy) was decreased by 76% in those cells treated additionally with letrozole (0.7 μM) compared with those receiving radiotherapy alone (P = 0.009). Growth inhibition, assessed either by cell number (P = 0.009) or by the MTT assay (P = 0.02), was increased after 12 days of the combination treatment. Compared with radiation alone, the combination of radiation and letrozole produced a significant decrease in radiation-induced G(2 )phase arrest and a decrease of cells in the S phase, with cell redistribution in the G(1 )phase. CONCLUSIONS: These radiobiological results may form the basis for concurrent use of letrozole and radiation as postsurgical adjuvant therapy for breast cancer

Dosimetric comparison between coplanar and non coplanar field radiotherapy for ethmoid sinus cancer

<p>Abstract</p> <p>Background</p> <p>To compare non coplanar field (NCF) with coplanar field (CF) -intensity-modulated radiotherapy (IMRT) planning for ethmoid cancer.</p> <p>Methods</p> <p>Seven patients treated with NCF IMRT for ethmoid cancer were studied. A CF IMRT optimization was prepared with the same constraints as for the NCF treatment. The maximum point doses (D max) obtained for the different optic pathway structures (OPS) should differ no more than 3% from those achieved with the NCF IMRT plan. The distribution of the dose in the target volume and in the critical structures was compared between the two techniques, as well as the Conformity (CI) and the Homogeneity Indexes (HI) in the target volume.</p> <p>Results</p> <p>We noted no difference between the two techniques in the OPS for the D1, D2, and D5%, in the inner ear and controlateral lens for the average Dmax, in the temporo-mandibular joints for the average mean dose, in the cord and brainstem for the average D1%. The dose-volume histograms were slightly better with the NCF treatment plan for the planning target volume (PTV) with a marginally better HI but no impact on CI. We found a great improvement in the PTV coverage with the CF treatment plan for two patients with T4 tumors.</p> <p>Conclusion</p> <p>IMRT is one of the treatment options for ethmoid cancer. The PTV coverage is optimal without compromising the protection of the OPS. The impact of non coplanar versus coplanar set up is very slight.</p