Intensity-modulated Radiotherapy In Patients Research Articles

Assessing software upgrades, plan properties and patient geometry using intensity modulated radiation therapy (IMRT) complexity metrics

The aim of this study is to compare the sensitivity of different metrics to detect differences in complexity of intensity modulated radiation therapy (IMRT) plans following upgrades, changes to planning parameters, and patient geometry. Correlations between complexity metrics are also assessed. A program was developed to calculate a series of metrics used to describe the complexity of IMRT fields using monitor units (MUs) and multileaf collimator files: Modulation index (MI), modulation complexity score (MCS), and plan intensity map variation (PIMV). Each metric, including the MUs, was used to assess changes in beam complexity for six prostate patients, following upgrades in the inverse planning optimization software designed to incorporate direct aperture optimization (DAO). All beams were delivered to a 2D ionization chamber array and compared to those calculated using gamma analysis. Each complexity metric was then calculated for all beams, on a different set of six prostate IMRT patients, to assess differences between plans calculated using different minimum field sizes and different maximum segment numbers. Different geometries, including CShape, prostate, and head and neck phantoms, were also assessed using the metrics. Correlations between complexity metrics were calculated for 20 prostate IMRT patients. MU, MCS, MI, and PIMV could all detect reduced complexity following an upgrade to the optimization leaf sequencer, although only MI and MCS could detect a reduction in complexity when one-step optimization (DAO) was employed rather than two-step optimization. All metrics detected a reduction in complexity when the minimum field size was increased from 1 to 4 cm and all apart from PIMV detected reduced complexity when the number of segments was significantly reduced. All metrics apart from MI showed differences in complexity depending on the treatment site. Significant correlations exist between all metrics apart from MI and PIMV for prostate IMRT patients. Treatment deliverability appeared to be more correlated with MI and MCS than MU or PIMV. The application of complexity metrics in the IMRT treatment planning process has been demonstrated. Complexity of treatment plans can vary for different inverse planning software versions and can depend on planning parameters and the treatment site. MCS is most suitable for inclusion within the cost function to limit complexity in IMRT optimization due to its sensitivity to complexity changes and correlation to treatment deliverability.

CyberKnife for prostate cancer: Is it cost-effective?

87 Background: The study assessed the cost-effectiveness of CyberKnife (CK) compared to surgery and radiation therapy for the treatment of prostate cancer (PC) from a third-party and societal perspective. Methods: For patients > 65 yrs with localized PC, a Markov model compared treatment with CK, intensity modulated radiation therapy (IMRT), surgery or proton therapy (PT). Following treatment, patients were at risk of long-term toxicity: genitourinary (GU); gastrointestinal (GI); and sexual dysfunction (SD). Long-term toxicity was defined as adverse events >grade 2 on Radiation Therapy Oncology Group scale occurring at least 12 months following treatment. Markov states included all possible combinations of GI, GU, and SD long-term toxicities, no toxicity, and death. During each year patients remained in the same Markov state or died. Costs and utilities were assigned using published sources. Toxicity probabilities were derived using meta-analytical techniques to pool results from multiple studies. It was assumed that long-term disease control would not differ across treatments. The model projected expected lifetime costs and quality adjusted life years (QALYs) for each treatment and incremental cost-effectiveness of CK vs comparators as cost per QALY gained. Costs from societal perspective included lost productivity. Extensive sensitivity analyses were conducted. Results: Surgery was the least expensive treatment option followed by CK. CK patients had higher expected QALYs (8.11) than other treatment options (7.72- 8.06). From a payer perspective, total lifetime costs were $25,904, $22,295, $38,915, and $58,100 for CK, surgery, IMRT and PT, respectively. Incremental cost per QALY gained for CK versus Surgery was $9,200/QALY. Compared to IMRT and PT, CK was less costly and resulted in higher QALYs (dominance). At a threshold of $50,000/QALY, CK was cost effective in 86%, 79%, and 91% of simulations compared to surgery, IMRT, and PT, respectively. From a societal perspective, CK costs $4,200/QALY compared to surgery and remained dominant vs IMRT and PT. Results were most sensitive to costs of surgery and CK. Conclusions: Initial CK costs are higher than surgery, but CK patients have better quality of life. CK patients have lower lifetime costs and higher QALYs than IMRT and PT patients. [Table: see text]

Improved Planning Time and Plan Quality Through Multicriteria Optimization for Intensity-Modulated Radiotherapy

To test whether multicriteria optimization (MCO) can reduce treatment planning time and improve plan quality in intensity-modulated radiotherapy (IMRT). Ten IMRT patients (5 with glioblastoma and 5 with locally advanced pancreatic cancers) were logged during the standard treatment planning procedure currently in use at Massachusetts General Hospital (MGH). Planning durations and other relevant planning information were recorded. In parallel, the patients were planned using an MCO planning system, and similar planning time data were collected. The patients were treated with the standard plan, but each MCO plan was also approved by the physicians. Plans were then blindly reviewed 3 weeks after planning by the treating physician. In all cases, the treatment planning time was vastly shorter for the MCO planning (average MCO treatment planning time was 12 min; average standard planning time was 135 min). The physician involvement time in the planning process increased from an average of 4.8 min for the standard process to 8.6 min for the MCO process. In all cases, the MCO plan was blindly identified as the superior plan. This provides the first concrete evidence that MCO-based planning is superior in terms of both planning efficiency and dose distribution quality compared with the current trial and error-based IMRT planning approach.

Dose uncertainty in radiotherapy of patients with head and neck cancer measured by in vivo ESR/alanine dosimetry using a mouthpiece

In order (i) to evaluate the dose uncertainty of the mouthpiece in daily use during intensity-modulated radiotherapy of patients with head and neck cancer, and (ii) to present a system for in vivo dosimetry of the oral mucosa, we equipped the mouthpiece with alanine dosimeter probes for in vivo dosimetry. The aim was to determine the dose uncertainty caused by the daily positioning of the mouthpiece during dynamic treatment techniques. During IMRT radiotherapy of patients with head and neck cancer, the doses accumulated next to the mucosa were measured in five patients and compared to the dose calculated by the treatment planning system. The comparison of the applied and measured dose for each measurement point showed in six of the eight alanine probe positions a good agreement within the given relative combined standard uncertainty of less than 4.5% for a accumulated dose of 30 Gy and less than 4.6% for an accumulated dose of 8 Gy, respectively. In two of the eight alanine probe positions the applied and measured doses differed by 7.7% and 8.2% from each other. The dominant contribution to the overall uncertainty for the in vivo measurements was the positioning of the dosimeter probes in the patient's body and their corresponding localization in the CT data as well as the inaccuracy of the available algorithm for dose distribution calculation at the low-density material/soft tissue interface between the mouthpiece and the mucosa. Regarding our results, we refrain from the use of a mouthpiece during dynamic treatments such as IMRT.

On the use of computed radiography plates for quality assurance of intensity modulated radiation therapy dose distributions

As traditional film is phased out in most radiotherapy centers, computed radiography (CR) systems are increasingly being purchased as a replacement. CR plates can be used for patient imaging, but may also be used for a variety of quality assurance (QA) purposes and can be calibrated in terms of dose. This study looks at their suitability for verification of intensity modulated radiation therapy (IMRT) dose distributions. A CR plate was calibrated in terms of the relative dose and the stability of response over 1 year was studied. The effect of exposing the CR plate to ambient light and of using different time delays before scanning was quantified. The CR plate was used to verify the relative dose distributions for ten IMRT patients and the results were compared to those obtained using a two dimensional (2D) diode array. Exposing the CR plate to 10 s of ambient light between irradiation (174 cGy) and scanning erased approximately 80% of the signal. Changes in delay time between irradiation and scanning also affected the measurement results. The signal on the plate was found to decay at a rate of approximately 3.6 cGy/min in the first 10 min after irradiation. The use of a CR plate for IMRT patient-specific QA resulted in a significantly lower distance to agreement (DTA) and gamma pass rate than when using a 2D diode array for the measurement. This was primarily due to the over-response of the CR phosphor to low energy scattered radiation. For the IMRT QA using the CR plate, the average gamma pass rate was 97.3%. For the same IMRT QA using a diode array, the average gamma pass rate was 99.7%. The gamma criteria used were 4% dose difference and 4 mm DTA for head and neck treatments and 3% dose difference and 3 mm DTA for prostate treatments. The gamma index tolerance was 1. The lowest 10% of the dose distribution was excluded from all gamma and DTA analyses. Although the authors showed that CR plates can be used for patient specific IMRT QA, the practical problems such as the over-response to low energy scatter and signal fading with light exposure and time mean that alternative detectors such as radiochromic film or diode arrays will be a more sensible choice for most radiotherapy departments.

Effects of Intensity-modulated Radiotherapy on Human Oral Microflora

This study aimed to evaluate changes in the biodiversity of the oral microflora of patients with head and neck cancer treated with postoperative intensity-modulated radiotherapy (IMRT) or conventional radiotherapy (CRT). Pooled dental plaque samples were collected during the radiation treatment from patients receiving IMRT (n = 13) and CRT (n = 12). Denaturing gradient gel electrophoresis (DGGE) was used to analyze the temporal variation of these plaque samples. The stimulated and unstimulated salivary flow rates were also compared between IMRT and CRT patients. Reductions in the severity of hyposalivation were observed in IMRT patients compared with CRT patients. We also observed that the temporal stability of the oral ecosystem was significantly higher in the IMRT group (69.96 ± 7.82%) than in the CRT group (51.98 ± 10.45%) (P < 0.05). The findings of the present study suggest that IMRT is more conducive to maintaining the relative stability of the oral ecosystem than CRT.

Treatment of locally advanced carcinomas of head and neck with intensity-modulated radiation therapy (IMRT) in combination with cetuximab and chemotherapy: the REACH protocol

BackgroundPrimary treatment of carcinoma of the oro-/hypopharynx or larynx may consist of combined platinum-containing chemoradiotherapy. In order to improve clinical outcome (i.e. local control/overall survival), combined therapy is intensified by the addition of the EGFR inhibitor cetuximab (Erbitux®). Radiation therapy (RT) is carried out as intensity-modulated RT (IMRT) to avoid higher grade acute and late toxicity by sparing of surrounding normal tissues.Methods/DesignThe REACH study is a prospective phase II study combining chemoradiotherapy with carboplatin/5-Fluorouracil (5-FU) and the monoclonal epidermal growth factor-receptor (EGFR) antibody cetuximab (Erbitux®) as intensity-modulated radiation therapy in patients with locally advanced squamous-cell carcinomas of oropharynx, hypopharynx or larynx.Patients receive weekly chemotherapy infusions in the 1st and 5th week of RT. Additionally, cetuximab is administered weekly throughout the treatment course. IMRT is delivered as in a classical concomitant boost concept (bid from fraction 16) to a total dose of 69,9 Gy.DiscussionPrimary endpoint of the trial is local-regional control (LRC). Disease-free survival, progression-free survival, overall survival, toxicity, proteomic and genomic analyses are secondary endpoints. The aim is to explore the efficacy as well as the safety and feasibility of this combined radioimmunchemotherapy in order to improve the outcome of patients with advanced head and neck cancer.Trial registrationISRCTN87356938

Salivary Gland Tumors Treated With Adjuvant Intensity-Modulated Radiotherapy With or Without Concurrent Chemotherapy

To analyze the recent single-institution experience of patients with salivary gland tumors who had undergone adjuvant intensity-modulated radiotherapy (IMRT), with or without concurrent chemotherapy. We performed a retrospective analysis of 35 salivary gland carcinoma patients treated primarily at the Dana-Farber Cancer Institute between 2005 and 2010 with surgery and adjuvant IMRT. The primary endpoints were local control, progression-free survival, and overall survival. The secondary endpoints were acute and chronic toxicity. The median follow-up was 2.3 years (interquartile range, 1.2-2.8) among the surviving patients. The histologic types included adenoid cystic carcinoma in 15 (43%), mucoepidermoid carcinoma in 6 (17%), adenocarcinoma in 3 (9%), acinic cell carcinoma in 3 (9%), and other in 8 (23%). The primary sites were the parotid gland in 17 (49%), submandibular glands in 6 (17%), tongue in 4 (11%), palate in 4 (11%), and other in 4 (11%). The median radiation dose was 66 Gy, and 22 patients (63%) received CRT. The most common chemotherapy regimen was carboplatin and paclitaxel (n = 14, 64%). A trend was seen for patients undergoing CRT to have more adverse prognostic factors, including Stage T3-T4 disease (CRT, n = 12, 55% vs. n = 4, 31%, p = .29), nodal positivity (CRT, n = 8, 36% vs. n = 1, 8%, p = .10), and positive margins (n = 13, 59% vs. n = 5, 38%, p = .30). One patient who had undergone CRT developed an in-field recurrence, resulting in an overall actuarial 3-year local control rate of 92%. Five patients (14%) developed distant metastases (1 who had undergone IMRT only and 4 who had undergone CRT). Acute Grade 3 mucositis, esophagitis, and dermatitis occurred in 8%, 8%, and 8% (1 each) of IMRT patients and in 18%, 5%, and 14% (4, 1, and 3 patients) of the CRT group, respectively. No acute Grade 4 toxicity occurred. The most common late toxicity was Grade 1 xerostomia (n = 8, 23%). Treatment of salivary gland malignancies with postoperative IMRT was well tolerated with a high rate of local control. Chemoradiotherapy resulted in excellent local control in a subgroup of patients with adverse prognostic factors and might be warranted in select patients.

Comparison of intensity‐modulated radiotherapy and 3‐dimensional conformal radiotherapy as adjuvant therapy for gastric cancer

The current study was performed to compare the clinical outcomes and toxicity in patients treated with postoperative chemoradiotherapy for gastric cancer using intensity-modulated radiotherapy (IMRT) versus 3-dimensional conformal radiotherapy (3D CRT). Fifty-seven patients with gastric or gastroesophageal junction cancer were treated postoperatively: 26 with 3D CRT and 31 with IMRT. Concurrent chemotherapy was capecitabine (n=31), 5-fluorouracil (5-FU) (n=25), or none (n=1). The median radiation dose was 45 Gy. Dose volume histogram parameters for kidney and liver were compared between treatment groups. The 2-year overall survival rates for 3D CRT versus IMRT were 51% and 65%, respectively (P=.5). Four locoregional failures occurred each in the 3D CRT (15%) and the IMRT (13%) patients. Grade>or=2 acute gastrointestinal toxicity was found to be similar between the 3D CRT and IMRT patients (61.5% vs 61.2%, respectively) but more treatment breaks were needed (3 vs 0, respectively). The median serum creatinine from before radiotherapy to most recent creatinine was unchanged in the IMRT group (0.80 mg/dL) but increased in the 3D CRT group from 0.80 mg/dL to 1.0 mg/dL (P=.02). The median kidney mean dose was higher in the IMRT versus the 3D CRT group (13.9 Gy vs 11.1 Gy; P=.05). The median kidney V20 was lower for the IMRT versus the 3D CRT group (17.5% vs 22%; P=.17). The median liver mean dose for IMRT and 3D CRT was 13.6 Gy and 18.6 Gy, respectively (P=.19). The median liver V30 was 16.1% and 28%, respectively (P<.001). Adjuvant chemoradiotherapy was well tolerated. IMRT was found to provide sparing to the liver and possibly renal function.

Vector Analysis of Prostate Patient Setup With Image-Guided Radiation Therapy via kV Cone Beam Computed Tomography

To analyze the daily setup variations in a cohort of intensity-modulated radiation therapy (IMRT) prostate cancer patients who had received daily image-guided RT without the use of fiducial markers to determine if daily image guidance is necessary. 2134 Kilovoltage (kV) cone beam computed tomography (CBCT) images were analyzed, with three shifts recorded for each image. The number of times that the vector of the combined shifts would have exceeded the planning tumor volume (PTV) margin was tallied. Then, the average scalar shift of the first five images was removed from all subsequent images for a given patient, and the number of days for which the shift vector was greater than the three-dimensional clinical tumor volume-PTV (3D CTV-PTV) margin (8 mm, created with rolling ball technique) was recorded. Additionally, the scalar shifts from every other fraction were studied to determine if the individual patient's shift vector would be adequately sampled if CBCT was not performed daily, thus reducing patient imaging dose without compromising treatment quality. There were 297 cases where the vector shift was initially greater than the PTV margin. By correcting each patient's data set by the average shift of their first five images the total was 248 cases. By considering only every other image of each patient data set (after correction for the first 5 days), only 137 days in which the CTV was outside the PTV would have been seen. Daily imaging is recommended for prostate cancer IMRT patients in order to know the 3D (vector) position of the CTV and to ensure that it is always within the PTV margin. Correcting the data set by the average shift from the first 5 days reduces the overall number of outlier days but does not eliminate them completely.

Adaptive Planning in Intensity-Modulated Radiation Therapy for Head and Neck Cancers: Single-Institution Experience and Clinical Implications

Anatomic changes and positional variability during intensity-modulated radiation therapy (IMRT) for head and neck cancer can lead to clinically significant dosimetric changes. We report our single-institution experience using an adaptive protocol and correlate these changes with anatomic and positional changes during treatment. Twenty-three sequential head and neck IMRT patients underwent serial computed tomography (CT) scans during their radiation course. After undergoing the planning CT scan, patients underwent planned rescans at 11, 22, and 33 fractions; a total of 89 scans with 129 unique CT plan combinations were thus analyzed. Positional variability and anatomic changes during treatment were correlated with changes in dosimetric parameters to target and avoidance structures between planning CT and subsequent scans. A total of 15/23 patients (65%) benefited from adaptive planning, either due to inadequate dose to gross disease or to increased dose to organs at risk. Significant differences in primary and nodal targets (planning target volume, gross tumor volume, and clinical tumor volume), parotid, and spinal cord dosimetric parameters were noted throughout the treatment. Correlations were established between these dosimetric changes and weight loss, fraction number, multiple skin separations, and change in position of the skull, mandible, and cervical spine. Variations in patient positioning and anatomy changes during IMRT for head and neck cancer can affect dosimetric parameters and have wide-ranging clinical implications. The interplay between random positional variability and gradual anatomic changes requires careful clinical monitoring and frequent use of CT- based image-guided radiation therapy, which should determine variations necessitating new plans.

Intensity-Modulated Radiotherapy in Patients with Cervical Cancer. An intra-individual Comparison of Prone and Supine Positioning

BackgroundChemoradiation for cervical cancer patients is associated with considerable gastrointestinal toxicity. Intensity-modulated radiotherapy (IMRT) has demonstrated superiority in terms of target coverage and normal tissue sparing in comparison to conventional 3D planning in gynaecological malignancies. Whether IMRT in prone (PP) or supine position (SP) might be beneficial for cervical cancer patients remains partially unanswered.Methods10 patients on FIGO stage IB-III cervical cancer, 6 patients for definitive and 4 patients for adjuvant external beam pelvic RT, were planned in PP and SP using a 7-field IMRT technique. IMRT plans for PP and SP (mean dose, Dmean 50.4 Gy) were optimized in terms of PTV coverage (1st priority) and small bowel sparing (2nd priority). A comparison of DVH parameters for PTV, small bowel, bladder, and rectum was performed.ResultsThe comparison showed a similar PTV coverage of 95% of the prescribed dose and for target conformity in IMRT plans (PP, SP). PTV, rectum and bladder volumes were comparable for PP and SP. Significantly larger volumes of small bowel were found in PP (436 cc, + 35%, p = 0.01). PP decreased the volume of small bowel at 20-50.4 Gy (p < 0.05) and increased the rectum volumes covered by doses from 10-40 Gy (p < 0.01), the V50.4 was < 5% in both treatment positions. Bladder sparing was significant better at 50.4 Gy (p = 0.03) for PP.ConclusionIn this dosimetric study, we demonstrated that pelvic IMRT in prone position for patients with cervical cancer seems to be beneficial in reducing small bowel volume at doses ≥20 Gy while providing similar target coverage and target conformity. The use of frequent image guidance with KV (kilovolt) or MV (megavolt) computertomography can reduce set-up deviations, and treatment in prone position can be done with a higher set-up accuracy. Clinical outcome studies are needed to affirm lower toxicity.

SU‐GG‐J‐65: CBCT Image Guidance for Head and Neck IMRT Radiation Therapy—A Study on the Tumor Coverage and Critical Structure Avoidance

Purpose: Cone beam computed tomography (CBCT) is becoming more prevalently used for image‐guided radiation therapy (IGRT). The ideal CBCT frequency and protocol will limit patient imaging dose, while insuring the accuracy of the radiation therapy (RT). We herein examine the effects of a possible CBCT imaging protocol on the delivered RT. Methods and Materials: The intensity modulated radiation therapy (IMRT) plans for 6 head and neck cancer patients undergoing IGRT with CBCT were retrospectively studied. The CBCT protocol called for daily IGRT for the first treatment week, followed by twice‐weekly imaging for the remaining RT fractions. The statistics of the IGRT patient set‐up shifts throughout the treatment course was used to create the treatment dose for non‐IGRT days using our in‐house TPS PlanUNC. The cumulative dose from the entire treatment course is the sum of the non‐IGRT daily doses and the planned daily doses for IGRT days. The resulting cumulative doses to the clinical target volume (CTV) and critical structures were examined.Results: The delivered treatment plans maintained the CTV treatment planning goals for 6 patients. Incorporating the IGRT shift statistics caused the CTV of one patient to be under dosed. The hotspots for the optic chiasm, cord, and brainstem were all within the treatment goals, and the absolute doses were within 5% of the planned RT. The dose constraints for the larynx and parotids were all maintained in the delivered treatment plans.Conclusions: The proposed CBCT protocol is sufficient for accurate RT delivery to the target volumes and critical structures of head and neck IMRT patients.

Intensity-modulated Radiation Therapy Versus Para-aortic Field Radiotherapy to Treat Para-aortic Lymph Node Metastasis in Cervical Cancer: Prospective Study

To compare dosimetry, efficacy, and toxicity of intensity-modulated radiation therapy (IMRT) with para-aortic field radiotherapy in patients with para-aortic lymph node (PALN) metastasis of cervical cancer. This prospective study examined 60 patients with cervical cancer with PALN metastasis who underwent whole-pelvis radiotherapy followed by brachytherapy between November 1, 2004 and May 31, 2008. After 3 cycles of chemotherapy, patients were serially allocated into two groups and treated with IMRT or para-aortic field RT at doses of 58-68 Gy and 45-50 Gy, respectively. Treatment response was evaluated and toxicities were assessed. Patients in the IMRT group were treated with both para-aortic field RT and IMRT in order to compare the exposure dose of organs at risk. In the IMRT group, the mean dose delivered to the planning target volume was 67.5 Gy. At least 99% of the gross tumor volume received effective coverage and radical dose (median, 63.5 Gy; range, 54.5-66) during treatment. IMRT plans yielded better dose conformity to the target and better sparing of the spinal cord and small intestine than para-aortic field RT. The IMRT patients experienced less acute and chronic toxicities. The IMRT group also had higher 2- and 3-year survival rates than the para-aortic RT group (2-year, 58.8% vs 25.0%, P = 0.019; 3-year, 36.4% vs 15.6%, P = 0.016). However, no significant difference was found in 1-year survival (67.7% vs 51.3%, P =0.201). The median survival in the IMRT group was 25 months (range, 3 to 37 months). The actuarial overall survival, disease-free survival, and locoregional control rates at 2 years were 67%, 77%, and 88%, respectively, in the IMRT group. IMRT provides better clinical outcomes than para-aortic field radiotherapy in patients with PALN metastasis. However, cervical local and distal recurrence remain a problem. Long-term follow-up and studies involving more patients are needed to confirm our results.

Pre-treatment verification of intensity modulated radiation therapy plans using a commercial electronic portal dosimetry system

We commissioned a commercially available portal dosimetry system for quality assurance of intensity modulated radiation therapy (IMRT) treatment plans. The system included gamma analysis software to compare the measured and predicted fluence maps from individual IMRT fields. The portal dosimetry system was tested using six head and neck IMRT patient plans, and we demonstrated that the accuracy of the alignment of measured and predicted images improved by retracting and repositioning the electronic portal imaging device (EPID) at each new gantry angle. The mean gamma score (fraction of pixels passing the gamma criteria) for the six test plans (after initial testing and using the EPID retracting and repositioning method) was 0.987 (2SD = 0.018), using gamma criteria of a dose difference of 2% of the maximum field dose and 2 mm distance to agreement. The mean gamma score was 0.989 (2SD = 0.017) for 24 head and neck IMRT patient plans carried out with portal dosimetry. Using gamma criteria of 2% maximum field dose and 2 mm distance to agreement, a gamma score tolerance of 0.980 is a useful way of highlighting only those fields requiring further analysis. Portal dosimetry is a quick way of assessing individual field fluence distributions and can be integrated into an IMRT quality assurance programme.

Phase I dose-finding study of paclitaxel with panitumumab, carboplatin and intensity-modulated radiotherapy in patients with locally advanced squamous cell cancer of the head and neck

BackgroundPanitumumab has the potential to improve the therapeutic ratio of concurrent chemoradiotherapy for squamous cell carcinoma of the head and neck (SCCHN). Patients and methodsThis phase I dose-finding study investigated escalating doses of paclitaxel (Taxol) given concurrently with panitumumab, carboplatin and intensity-modulated radiotherapy (IMRT) for stage III–IVB SCCHN. Untreated patients with oral cavity, oropharynx, larynx, hypopharynx or unknown primaries were eligible. Additional eligibility criteria included measurable disease, good performance status and no contraindication to therapy. Patients received weekly fixed doses of panitumumab and carboplatin plus escalating doses of paclitaxel with IMRT. ResultsNineteen patients were enrolled on to two dose levels (DLs): weekly paclitaxel 15 mg/m2 (n=3) and 30 mg/m2 (n=16). One dose-limiting toxicity occurred in DL 2, which was declared the maximum tolerated dose. All patients experienced mucositis, primarily grade 3 or more. Oral pain, xerostomia, dysphagia, weight loss, dermatitis, nausea and acneiform rash were frequent. All patients had partial response according to RECIST, whereas the overall complete clinical response rate was 95%. At median follow-up of 21 months, 18 of 19 patients (95%) remained disease free. ConclusionsPanitumumab, carboplatin, paclitaxel and IMRT are well tolerated and appear highly active in the treatment of SCCHN. Further study of this regimen in SCCHN is warranted.

Simultaneous Integrated Boost Intensity-Modulated Radiotherapy in Patients With High-Grade Gliomas

We analyzed outcomes of simultaneous integrated boost (SIB) intensity-modulated radiotherapy (IMRT) in patients with high-grade gliomas, compared with a literature review. Forty consecutive patients (WHO grade III, 14 patients; grade IV, 26 patients) treated with SIB-IMRT were analyzed. A dose of 2.0 Gy was delivered to the planning target volume with a SIB of 0.4 Gy to the gross tumor volume with a total dose of 60 Gy to the gross tumor volume and 50 Gy to the planning target volume in 25 fractions during 5 weeks. Twenty patients received temozolomide chemotherapy. At a median follow-up of 13.4 months (range, 3.7-55.9 months), median survival was 14.8 months. One- and 2-year survival rates were 78% and 65%, respectively, for patients with grade III tumors and 56% and 31%, respectively, for patients with grade IV tumors. Age (≤50 vs. >50), grade (III vs. IV), subtype (astrocytoma vs. oligodendroglioma or mixed), and a Zubrod performance score (0-1 vs. >2) were predictive of survival. Of 25 (63%) patients who had recurrences, 17 patients had local failure, 9 patients had regional failure, and 1 patient had distant metastasis. Toxicities were acceptable. SIB-IMRT with the dose/fractionation used in this study is feasible and safe, with a survival outcome similar to the historical control. The shortening of treatment time by using SIB-IMRT may be of value, although further investigation is warranted to prove its survival advantage.

Effect of Brain Stem and Dorsal Vagus Complex Dosimetry on Nausea and Vomiting in Head and Neck Intensity-Modulated Radiation Therapy

Intensity-modulated radiation therapy (IMRT) is becoming the treatment of choice for many head and neck cancer patients. IMRT reduces some toxicities by reducing radiation dose to uninvolved normal tissue near tumor targets; however, other tissues not irradiated using previous 3D techniques may receive clinically significant doses, causing undesirable side effects including nausea and vomiting (NV). Irradiation of the brainstem, and more specifically, the area postrema and dorsal vagal complex (DVC), has been linked to NV. We previously reported preliminary hypothesis-generating dose effects associated with NV in IMRT patients. The goal of this study is to relate brainstem dose to NV symptoms. We retrospectively studied 100 consecutive patients that were treated for oropharyngeal cancer with IMRT. We contoured the brainstem, area postrema, and DVC with the assistance of an expert diagnostic neuroradiologist. We correlated dosimetry for the 3 areas contoured with weekly NV rates during IMRT. NV rates were significantly higher for patients who received concurrent chemotherapy. Post hoc analysis demonstrated that chemoradiation cases exhibited a trend towards the same dose-response relationship with both brainstem mean dose ( p = 0.0025) and area postrema mean dose ( p = 0.004); however, both failed to meet statistical significance at the p ≤ 0.002 level. Duration of toxicity was also greater for chemoradiation patients, who averaged 3.3 weeks with reported Common Terminology Criteria for Adverse Events (CTC-AE), compared with an average of 2 weeks for definitive RT patients ( p = 0.002). For definitive RT cases, no dose-response trend could be ascertained. The mean brainstem dose emerged as a key parameter of interest; however, no one dose parameter (mean/median/EUD) best correlated with NV. This study does not address extraneous factors that would affect NV incidence, including the use of antiemetics, nor chemotherapy dose schedule specifics before and during RT. A prospective study will be required to depict exactly how IMRT dose affects NV.

Cognitive Function Before and After Intensity-Modulated Radiation Therapy in Patients With Nasopharyngeal Carcinoma: A Prospective Study

To evaluate the effects of radiation therapy (RT) on neurocognitive function in patients with nasopharyngeal carcinoma (NPC). Thirty patients with NPC treated with intensity-modulated RT were included. Dose-volume histograms of the temporal lobes were obtained in every patient. Neurocognitive tests were administered individually to each patient 1 day before initiation of RT and at least 12 months after completion of RT. Cognitive functioning status was evaluated as change in scores over time. Among the total of 30 patients, 23 patients (76.7%) had significantly lower post-RT cognitive functioning scores compared with their pre-RT scores (p = 0.033). The cognitive functioning scores had significantly declined in the domains of short-term memory, language abilities, and list-generating fluency (p = 0.020, 0.023, and 0.001, respectively). Compared with patients with a mean dose to the temporal lobes of 36 Gy or less, patients with a mean dose of greater than 36 Gy had a significantly greater reduction in cognitive functioning scores (p = 0.017). Patients in whom V60 of the temporal lobes (i.e., the percentage of the temporal lobe volume that had received >60 Gy) was greater than 10% also had a greater reduction in cognitive functioning scores than those in whom V60 was 10% or less (p = 0.039). The results of our study indicated that RT could have deleterious effects on cognitive function in patients with NPC. Efforts should be made to reduce the radiation dose and irradiated volume of temporal lobes without compromising the coverage of target volume.

Cone-Beam CT Assessment of Interfraction and Intrafraction Setup Error of Two Head-and-Neck Cancer Thermoplastic Masks

To prospectively compare setup error in standard thermoplastic masks and skin-sparing masks (SSMs) modified with low neck cutouts for head-and-neck intensity-modulated radiation therapy (IMRT) patients. Twenty head-and-neck IMRT patients were randomized to be treated in a standard mask (SM) or SSM. Cone-beam computed tomography (CBCT) scans, acquired daily after both initial setup and any repositioning, were used for initial and residual interfraction evaluation, respectively. Weekly, post-IMRT CBCT scans were acquired for intrafraction setup evaluation. The population random (sigma) and systematic (Sigma) errors were compared for SMs and SSMs. Skin toxicity was recorded weekly by use of Radiation Therapy Oncology Group criteria. We evaluated 762 CBCT scans in 11 patients randomized to the SM and 9 to the SSM. Initial interfraction sigma was 1.6 mm or less or 1.1 degrees or less for SM and 2.0 mm or less and 0.8 degrees for SSM. Initial interfraction Sigma was 1.0 mm or less or 1.4 degrees or less for SM and 1.1 mm or less or 0.9 degrees or less for SSM. These errors were reduced before IMRT with CBCT image guidance with no significant differences in residual interfraction or intrafraction uncertainties between SMs and SSMs. Intrafraction sigma and Sigma were less than 1 mm and less than 1 degrees for both masks. Less severe skin reactions were observed in the cutout regions of the SSM compared with non-cutout regions. Interfraction and intrafraction setup error is not significantly different for SSMs and conventional masks in head-and-neck radiation therapy. Mask cutouts should be considered for these patients in an effort to reduce skin toxicity.