CT Guided, Dose Painting IMRT for Nasopharyngeal Carcinoma

I. J. Radiation Oncology d Biology d Physics

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Volume 72, Number 1, Supplement, 2008

Intensity Modulated Radiation Therapy (IMRT) and Concomitant Chemotherapy for Advanced Stage Hypopharynx and Laryngeal Cancer

E. M. Landau1, K. J. Skinner1, E. C. Oppenheimer2, M. Haigentz1, R. V. Smith1, B. A. Schiff1, M. Garg1 1

Montefiore Medical Center, Bronx, NY, 2Yeshiva University, New York, NY

Purpose/Objective(s): To perform and interim outcome analysis of patients with advanced stage hypopharynx and laryngeal cancer patients treated with concomitant IMRT and chemotherapy. Materials/Methods: This is the first report on 37 consecutive patients with stage III+ IV hypopharynx and laryngeal squamous cell cancer treated with IMRT and concomitant cisplatin (100 mg/m2 day 1 and 21). IMRT was delivered using Simultaneous Integrated Boost Technique with Gross disease PTV receiving 69.96 Gy in 2.12 Gy/Fraction, High Risk PTV receiving 59.4 Gy in 1.8 Gy/Fraction and Sub clinical disease receiving 54.12 Gy in 1.64 Gy/Fraction. Contrast enhanced CT -PET co-registered images were used for treatment planning. The RTOG common toxicity scale was used to assess short and long-term toxicity. Results: Twenty-nine patients (78%) were Stage IV and 8 (22%) were stage III. 32 patients were treated definitively and 5 were treated post-operatively. The average treatment completion time was 53 days (SD ± 10). The rate of acute grade II mucositis, xerostomia and dysphagia were 42%, 22% and 30% respectively. Acute grade III oral mucositis, xerostomia and dysphagia rates were 8.6%, 3% and 21% respectively. Overall, no grade IV or higher toxicities were noted. The average absolute weight loss reported during treatment was 16.53lbs (STD 10.53), and the percent BMI lost was 10% (SD ± 6.56). The rate of prophylactic PEG placement and PEG placement during treatment were both 21%. 18% (n = 7) of patients required re-planning due to significant change in contour/treatment volumes. The average follow-up was 10 months (SD ± 5.8). The local recurrence free, regional recurrence free, metastases free, laryngectomy free rates and overall survival were 80 %, 88%, 71%, 84% and 81.8% respectively. The average time to failure was 260 days (SD ± 117). Late grade II and III xerostomia and dysphagia rates were 21% and 43% respectively with 14 patients remained PEG dependent at the time of analysis. Conclusions: Our on going analysis of these advanced stage cancers shows IMRT has a low rate of toxicities, and excellent regional control for these locally advanced laryngeal and hypopharyngeal cancer patients. Changes in BMI remains high and as such adaptive planning is needed to adjust for the patient’s changing contour. Author Disclosure: E.M. Landau, None; K.J. Skinner, None; E.C. Oppenheimer, None; M. Haigentz, None; R.V. Smith, None; B.A. Schiff, None; M. Garg, None.

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Quantifying the Shift Uncertainty in Daily Image Guidance and its Dosimetric Significance for Head and Neck IMRT

J. M. Holland, P. J. Gagnon, T. L. McDonald, L. Ku Oregon Health & Science University, Portland, OR Purpose/Objective(s): Uncertainty in image registration (or shift determination) is one of the key residual errors in image-guided radiotherapy (IGRT) for head and neck cancer. Our goal is to quantify the uncertainty in image-guided shift determination and evaluate its dosimetric significance. Materials/Methods: Retrospective daily IGRT 2D matching setup processes were performed for ten patients using a commercial off-line review program. Four bony landmarks in three distinct regions for image registration were chosen: the sella turcica and the bony nasal septum, C2 and C5 vertebral bodies. The acquired daily kV radiographs were registered to DRRs based on each of the four landmarks. This lead to three possible directional shifts from which we defined the uncertainty of the shift determination. The average of the uncertainty in daily shifts for each patient was calculated. Post-shift plans were generated by incorporating these uncertainty values. Comparison of these post-shift plans with the original plans demonstrates the dosimetric impact. Results: The uncertainties in the Anterior-Posterior (SAP) and Lateral directions (SLat) are larger than that of the Superior-Inferior direction (SSI). In seven out of the ten patients, the largest uncertainty is in SAP. Three patients have 3 mm or larger uncertainties. For all patients, the SSI is smaller than 1.0 mm. The median of SAP, SLat and SSI are 2.5 mm, 2.0 mm and 0.4 mm respectively. These uncertainties translate to a deviation in dose to critical structures. The largest differential doses to the spinal cord and parotids are 5.5 Gy and 4.1 Gy respectively. Conclusions: We have quantified the shift uncertainty in daily image guidance when using different bony landmarks. Our results confirm the dosimetric impact on head and neck IMRT. This uncertainty can be larger than any other factors of residual error, such as mechanical stability of the OBI and intra-fractional patient motion. These positional variations should be considered when designing treatment margins and when choosing bony landmarks for daily image-guided shifts. Author Disclosure: J.M. Holland, None; P.J. Gagnon, None; T.L. McDonald, None; L. Ku, None.

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PET/CT Guided, Dose Painting IMRT for Nasopharyngeal Carcinoma

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¨ nalan3, C. Tecimer4, G. Ko¨ksal4, S. Turkan1, S. Okkan5 S. Igdem , M. Altun1, G. Alc¸o1, T. Ercan1, B. Kara2, B. U 1 Metropolitan Hospital, Dept of Radiation Oncology, Istanbul, Turkey, 2Metropolitan Hospital, Dept of Radiology, Istanbul, Turkey, 3Metropolitan Hospital, Dept of Nuclear Medicine, Istanbul, Turkey, 4Metropolitan Hospital, Dept of Medical Oncology, Istanbul, Turkey, 5Istanbul Bilim University, Dept of Radiation Oncology, Istanbul, Turkey

Purpose/Objective(s): To evaluate the impact of F18-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) guided Intensity Modulated Radiotherapy (IMRT) on locoregional control and general outcome in patients with nasopharyngeal carcinoma (NPC). Materials/Methods: Between June 2005 and January 2007, 19 patients with NPC received PET/CT guided IMRT. Median patient age was 48 years. Stage at presentation was II in 6, III in 8, and IV in 5 patients. 80% of the patients had WHO type III disease. All imaging and data acquisition was performed on an integrated PET/CT system in the treatment position. On the fused PET/CT

Proceedings of the 50th Annual ASTRO Meeting images, FDG avid lesions as gross target volume (GTV) were contoured visually by a team of radiation oncologist, neuroradiologist and nuclear medicine physician. All patients were treated in 33 fractions using dose painting, extended whole field IMRT with a dose of 70 Gy to the GTV and 59.4 Gy and 54 Gy to the high risk and low risk clinical tumor volumes, respectively. All patients received neoadjuvant and/or concurrent platinum based chemotherapy. Toxicity data were scored using CTCAE v3.0. Results: Median follow-up from initiation of treatment was 24 months (14-28 months). PET/CT simulation revealed a second malignancy in the lung in 1 patient and a solitary bone metastasis in another patient. No stage migration was observed according to the N status. All patients had follow-up PET/CT imaging within a period of median 5 months (3-12 months) after the treatment and all of them had complete response. Follow-up PET/CT suspected a second malignancy in the colorectal system which turned out to be a rectosigmoid cancer after colonoscopic biopsy in 1 patient at 12 months. One patient failed within the high dose (70 Gy) volume at 24 months and one patient failed in the lungs at 20 months. All patients had regional control and all patients were alive at the time of this analysis. Grade 3 acute toxicity rates for mucositis was 36%, for pharyngeal dysphagia 22%, and grade 2 acute toxicity for mouth dryness was 86%. Ten percent and 26% of the patients experienced grade 2 late dysphagia and mouth dryness, respectively. One patient who presented with intracranial extension developed temporal lobe necrosis which resolved clinically after steroid therapy. Conclusions: Early findings of this single institution experience suggest that PET/CT guided, dose painting IMRT results in high locoregional disease control with acceptable toxicity in NPC patients. In addition PET/CT detected 2 second primaries and 1 distant disease in 3 different patients leading to alterations in patient management during different steps of the treatment process. ¨ nalan, None; C. Tecimer, Author Disclosure: S. Igdem, None; M. Altun, None; G. Alc¸o, None; T. Ercan, None; B. Kara, None; B. U None; G. Ko¨ksal, None; S. Turkan, None; S. Okkan, None.

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Retrospective Analysis of 271 Patients with T1N0M0 Glottic Laryngeal Cancer

M. Gultekin, E. Ozyar, M. Cengiz, U. Selek, G. Ozyigit, F. Akyol Hacettepe University, Department of Radiation Oncology, Ankara, Turkey Purpose/Objective(s): To analyze treatment results and prognostic factors in patients with T1N0M0 glottic laryngeal cancer treated with radiotherapy. Materials/Methods: In this study, 271 T1N0M0 glottic laryngeal cancer patients treated at our department with definitive radiotherapy between 1993 and 2007 were retrospectively evaluated. All patients were treated with curative intent. Thirteen patients were excluded from this analysis. There were 6 (2%) female and 252 (98%) male with a median age of 59 years (range, 35-86 years). Of the 258 patients, 226 (88%) had Stage T1a and 32 (12%) had Stage T1b according to AJCC staging system. The anterior commissure was involved in 40 (15%) patients. Patients were diagnosed with biopsy (76%), stripping (18%) or cordectomy (4%). Radiotherapy doses were given 2 to 2.3 Gy per fraction (median 2.3 Gy) to the total dose of 59.8-70 Gy (median 64.4 Gy). The overall treatment time ranged from 30 to 70 days (median 38). Median field size was 38 cm2 (range 22-132 cm2). The follow-up ranged from 4 to 159 months (Median 43 months). Results: Two and 5 year overall survival rate (OS) was 96% and 89%, locoregional control rate (LRC) was 89% and 88% and cause-specific survival rate (CSS) was 98% and 94%, respectively. Thirty-one patients (12%) had local recurrence and 2 patients (0.8%) had regional recurrence during follow-up. Two patients (1%) died due to second primary cancer and 5 patients died due to intercurrent disease. The patient and treatment variables tested included; sex (female vs. male), age (\60 vs. $60), T stage (T1a vs. T1b), subglottic extension (present vs. absent), anterior commissure involvement (present vs. absent) and fraction dose (2 vs. 2.3 Gy). The multivariate analysis did not reveal any significant factor. No grade IV or V acute complications were observed. Late complications were observed in a patient with tracheoesophageal fistula). Fifteen patients (6%) developed various second primary malignancies. Conclusions: Radiotherapy is an effective modality in patients with T1N0M0 glottic carcinoma which is a parallel finding to the literature. Author Disclosure: M. Gultekin, None; E. Ozyar, None; M. Cengiz, None; U. Selek, None; G. Ozyigit, None; F. Akyol, None.

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Prehistory of the M.D. Anderson Cancer Center Ovoids for the Treatment of Cervical Cancer

J. S. Yordy, P. Almond M.D. Anderson Cancer Center, Houston, TX Dr. Gilbert Fletcher published his first paper on the gynecological radiation applicators he had developed at the MD Anderson Hospital (MDAH) in Houston in 1955. At the beginning of the 1940s there were three main systems for treating gynecological cancer with radiation: the Paris, Manchester and Stockholm systems. During that decade, detailed analyses and the development of variations of these systems took place, especially in the United Kingdom. From the citations in Fletcher’s original paper it is clear that his thinking was influenced by the work of Neary and Donaldson at the Mt. Vernon Hospital in London, where they developed a single metal ovoid applicator with built-in shielding, as well as that of Lederman and Lamerton at the Royal Cancer Hospital, also in London, where they used the Spiers stereo-radiographic tube-shift method to determine dose around their applicators, following this up with in vivo measurements. Examination of the newly discovered primary notebook of Dr. Leonard Grimmett (chair of the Physics Department at MDAH), as well as published articles, provides evidence that Dr. Fletcher merged ideas from the London, Stockholm and Paris systems when creating the MDAH gynecological applicators. He retained the two-ovoid system from Manchester but made them from stainless steel instead of plastic and added tungsten shielding, the first time these two materials were combined in an ovoid. The metal vaginal vault-measuring instrument discussed by Lederman was modified to hold two ovoids, creating a colpostat, and in vivo measurements were initiated using a scintillation detector. Dr. Grimmett was involved in all aspects of the development of the gynecological radiation applicator system at MDAH. Original unpublished hand-written data from Dr. Grimmett’s laboratory notebook show the initial measured comparisons of dose distribution using small condenser chambers between the plastic unshielded ovoids and the shielded stainless steel ovoids, demonstrating a 10% attenuation of dose by the stainless steel compared to the plastic ovoids while retaining similar dose distributions, and also document the shielding effect of tungsten. From May through July 1950, Dr. Grimmett conducted a detailed analysis and modification of the Spiers tube-shift method for use

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