- Email: [email protected]
74 poster: PET Scan Guided Interstitial Brachytherapy in Cervical Cancer Patients with Clinically Suspected Residual Disease
R ESPONSE EVALUATION / FOLLOW UP mius muscle of NMRI mice and tumor cell death was induced by x-ray irradiation. Accumulation of the intravenously administered USPIO-E3 particles in treated and untreated TLT tumors was compared to the accumulation of control particles (ungrafted USPIO and USPIO grafted to a scrambled peptide) ex vivo by X-band EPR, and in vivo by L-band EPR and T2-weighted MRI. MRI and X-band EPR were also used to compare USPIO-E3 accumulation in three different tumor models presenting different degrees of radiosensitivity (fibrosarcoma FsaII
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73 poster MOLECULAR REMISSION AFTER NEOADJUVANT CHEMORADIATION IN MEDIASTINAL LYMPH NODE METASTASES AS DETECTED BY F-18 FDG PET IN PATIENTS WITH NSCLC V. Prasad1 , M. Schmuecking2 , R. P. Baum1 , C. P. Schneider3 , N. Presselt4 , J. Leonhardi5 , K. Hoeffken6 , K. M. Mueller7 , T. Wendt8 , R. Bonnet3 1 Z ENTRALKLINIK B AD B ERKA, Department of Nuclear Medicine / Center for P.E.T., Bad Berka, Germany 2 G REIZ C OUNTY H OSPITAL, Center for Radiology, Greiz, Germany 3 Z ENTRALKLINIK B AD B ERKA, Department of Pneumology, Bad Berka, Germany 4 Z ENTRALKLINIK B AD B ERKA, Department of Thoracic Surgery, Bad Berka, Germany 5 Z ENTRALKLINIK B AD B ERKA, Department of Radiology, Bad Berka, Germany 6 U NIVERSITY HOSPITAL J ENA, Department of Hematology / Oncology, Jena, Germany 7 U NIVERSITY H OSPITAL B ERGMANNSHEIL, Department of Pathology, Bochum, Germany 8 U NIVERSITY HOSPITAL J ENA, Department of Radiation Oncology, Jena, Germany
72 poster MOLECULAR IMAGING OF RADIATION RESPONSE IN PRECLINICAL MODELS USING A NOVEL SMALL ANIMAL RADIOTHERAPY SYSTEM G. Nelson1 , M. Vilalta2 , J. Pérez1 , M. Bazalova1 , A. Giaccia2 , E. Graves3 1 S TANFORD U NIVERSITY S CHOOL OF M EDICINE, Radiation Physics, Stanford, USA 2 S TANFORD U NIVERSITY S CHOOL OF M EDICINE, Division of Radiation Oncology , Stanford, USA 3 S TANFORD C ANCER C ENTER, Raditaion Oncoloy, Stanford, USA Purpose: Typical small animal irradiation methods are incapable of the spatial accuracy routinely achieved in a modern cancer center. To mitigate this, a microCT system was modified to produce a clinically similar system for small animal image-guided conformal radiotherapy. By collimating the x-ray beam from the microCT, beams as small as 1 mm at isocenter can be delivered to anesthetized subjects. Combined with a custom bed capable of 3D movement, arbitrary targets within a mouse can be imaged, localized, targeted, and irradiated. Application of this technology to mouse models of disease allows for exploration of functional imaging in radiotherapy using preclinical molecular imaging. The biological response of tissues to emerging radioand chemotherapies have been evaluated with γ H2AX immunohistochemistry, positron emission tomography (PET) with the tracers fluorodeoxyglucose (FDG), fluorothymidine (FLT), fluoroazomycin arabinoside (FAZA), and bioluminescence imaging (BLI). Materials: We evaluated the ability of the system to induce a biological response in a small target by conformally irradiating a spontaneous murine model of lung cancer. Immediately after treatment the mice were sacrificed and the tumors were excised, sectioned, and stained for γ H2AX stained to evaluate DNA double strand breaks. We investigated the effect of treatment on normal and neoplastic tissue by performing BLI and FDG and FLT PET scans before and after treatment to a variety of radiation doses to establish the dose response. Finally, the utility of combined radiotherapy and anti-HIF-1 chemotherapy was evaluated using BLI and FAZA PET. Results: The system is capable of accurate dose delivery. It is able to deliver dose to targeted areas while sparing others using radiation delivery techniques analogous to those commonly employed in the clinic. Dose fractionation is feasible and allows the system to deliver a greater total dose. Dose response of tissues was evident from serial BLI of tumors treated with radiation. Molecular imaging of therapeutic responses varied greatly between molecular targets and tumor types and encourages further study of the potential role of these imaging modalities in clinical radiation oncology. Conclusions: A system for clinically-relevant small animal image-guided conformal radiotherapy has been constructed, validated, and employed to investigate molecular imaging of radiation response using a variety of modalities.
Purpose: To evaluate the role of molecular remission in mediastinal lymph node metastases after neoadjuvant chemoradiation as detected by 18F FDG PET/CT, findings in 32 patients with NSCLC stage III were analyzed prospectively. Materials: Inclusion criteria: histologically confirmed NSCLC stage IIIA/IIIB. ECOG PS 0-1, adequate hematologic, renal, hepatic function. Primary end points: OS, DFS. Secondary end points: TTP, QoL, RR. Neoadjuvant treatment: 2-3 cycles of paclitaxel/carboplatin and a block of chemoradiation (45Gy, 1.5Gy b.i.d., concomitant paclitaxel/carboplatin) followed by surgery. Randomization: late (Arm1) vs. early (Arm2) chemoradiation. Staging: PET in addition to CT and/or MRI after randomization, second PET after completion of neoadjuvant therapy prior to surgery. Assessment of standardized uptake values (SUV) in primary tumor (PT) and all metastatic lymph nodes (LN). Documentation of involved LN as detected by PET and LN sampling during surgery according to Naruke/ATS-LCSG classification. Evaluation of histological regression grade (RG) and correlation with PET for PT and each LN. Molecular radiation treatment planning (MRTP) using fused PET/CT data. Evaluation of ’out-field’ and ’in-field’ recurrences after PET planned radiation treatment by follow-up studies using PET/CT, CT and MRI). Intent to treat analyses using Kaplan-Meier estimates, log rank tests and Cox multivariate models. Results: So far 32/210 eligible pts were analyzed (192 lymph node regions, 576 lymph nodes). Actuarial tumor specific survival: complete vs. incomplete metabolic remission after 60 months: 43% vs. 24% (p = .018), RG III/IIb (no/less than 10% of vital tumor cells) vs. RG IIa/I (more than 10% vital tumor cells) after 60 months: 46% vs. 18% (p < .006). So far, follow-up studies showed no mediastinal ’out-field’ recurrences in mediastinal lymph nodes which received no radiation treatment. ’In-field’ recurrences were observed in 11/32 pts, 7/11 pts had initially an incomplete remission after neoadjuvant chemoradiation. Conclusions: Molecular remission in mediastinal lymph nodes as detected by 18F-FDG PET correlates well with RG and may predict (long-term) therapeutic outcome in pts with stage III NSCLC. 18F-FDG PET precedes CT in measuring the tumor response. Integration of PET in clinical trials enables a more accurate therapy management. Our preliminary data of 32 pts suggest that an elective nodal irradiation (ENI) of inconspicuous lymph nodes as detected by PET may not be necessary for NSCLC stage III. 74 poster PET SCAN GUIDED INTERSTITIAL BRACHYTHERAPY IN CERVICAL CANCER PATIENTS WITH CLINICALLY SUSPECTED RESIDUAL DISEASE D. N. Sharma1 , G. K. Rath1 , S. Kumar2 , R. Kumar3 , P. K. Julka1 , P. Jagadesan1 , V. Subramani1 1 A LL I NDIA I NSTITUTE OF M EDICAL S CIENCES, Radiation Oncology, NewDelhi, India 2 A LL I NDIA I NSTITUTE OF M EDICAL S CIENCES, Gynaecology, NewDelhi, India 3 A LL I NDIA I NSTITUTE OF M EDICAL S CIENCES, Nuclear Medicine, NewDelhi, India Purpose: To evaluate the role of PET Scan guided consolidation interstitial brachytherapy (IBT) in cervical carcinoma patients with clinically suspected residual disease after 4 weeks of completion of concurrent chemoradiotherapy (CCRT). Materials: During the year 2006-2007, 23 cervical carcinoma patients having clinically suspected residual disease showing FDG uptake in the cervical/ para cervical region after 4 weeks of completion of the standard course of CCRT were enrolled into the study. Patients with clinically evident or frank residual disease were excluded from this study. Before consolidation IBT,
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the standard CCRT consisted of whole pelvis EBRT with 40 Gy in 22fractions over 4.5 weeks followed by 10 Gy in 5fractions over 1 week with midline shielding and then 3 sessions of weekly HDR intracavitary brachytherapy of 7 Gy each to Point A. Weekly chemotherapy (Cisplatin, 40 mg/sqm) was administered during the course of EBRT to all patients. Four weeks later, PET/CT Scan was done on dedicated PET-CT scanner (SIEMENS, BIOGRAPH 64) using 5-10 mCi of intravenous FDG. The consolidation therapy consisted of a single session of high dose rate (HDR) IBT with a dose of 8-10 Gy. IBT needles were inserted through the perineum using Martinez Universal Perineal Interstitial Template under the guidance of Trans-rectal ultrasound (TRUS). Treatment planning was done on Nucletron planning system (PLATO) using the CT Scan images. IBT treatment was carried out on Microselectron HDR remote after loading unit and the perineal template was removed immediately after completing the treatment. All patients were followed up monthly till 6 months, every 2 months till 1 year and then every 3-6 months thereafter. Results: Follow up period ranged from 3-18 months (median 11 months). Of 23 patients, 15 (65%) had pelvic disease control, 6 had pelvic failure, 1 had para-aortic node recurrence and 1 lung metastases. One patient had hematuria during postoperative period, which stopped after 24 hours. Overall late toxicity (grade III-IV) was noticed in 3 (13%) patients. Of them, 2 had recto-vaginal fistula and 1 had sub acute intestinal obstruction. Conclusions: In patients with cervical carcinoma having residual disease on PET scan after 4 weeks of completion of CCRT, consolidation treatment with single fraction of 8 Gy HDR IBT provides effective pelvic control rate and acceptable complication rate. It may be further studied with a larger sample size.
Materials: In a Phase I trial, 10 patients completed therapy with nelfinavir (1250mg bd D-2 to 45) and chemoradiation (Phase I 50.4Gy in 28#, Phase II 9.0Gy in 5# (D1 to 45) with concomitant Cisplatin 30mg/m2 + Gemcitabine 200mg/m2 (DL1) 300mg/m2 (DL2) D1, 8, 22, 29) for locally advanced pancreatic cancer. Response to treatment was evaluated with CT (RECIST criteria) and 18 FDG-PET CT (change in SUV) six weeks following completion of chemoradiotherapy and correlated with the pathological specimen in the 6 patients who underwent resection (all R0). Results: In the five evaluable resected patients with pre- and post-therapeutic 18 FDG-PET CT imaging the responses on 18 FDG-PET CT were superior to the responses on CT, however neither CT nor 18 FDG-PET CT were accurate predictors of pathological response. 18 FDG-PET CT showed a CR in four patients, three of whom had residual viable tumour on pathological examination (<10% viable tumour in two patients, but one patient had a ypT3N1 tumour with 50-80% viable tumour cells), and one patient who had a pCR.
75 poster RADIONUCLIDE EVALUATION OF RESPONSE TO NEOADJUVANT CHEMOTHERAPY IN BREAST CANCER PATIENTS O. Solodyannikova1 1
U KRAINIAN R ES .I NST. OF O NCOL ., Department of Nuclear Medicine, Kiev, Ukraine
Purpose: Searching of most informative and clinical based methods of estimation and prediction of chemotherapy treatment and monitoring among breast cancer (BC) patients is very acute medical problem, limiting advanced breast cancer treatment. The aim of present study was to evaluate whether tuomour clearance of 99mTc MIBI is capble to assess tumour response to neoadjuvant chemotherapy in patients with locally advanced BC. Materials: 40 BC patients planning for undergoing neoadjuvant chemotherapy were investigated 2-8 days prior to chemotherapy using scintimammography (SMG) with 99mTc- MIBI. Static scintimammography was performed 10 and 60 min. post intravenous injection of 400-550 MBq of 99mTc-MIBI. Time to half clearance (T1/2) of 99mTc MIBI was calculated in each patient from decay-corrected time-activity curves using monoexponential fitting. Chemotherapy was given as either standard AC courses (doxorubicin, cyclophosphamide) to 20 patients, as CEF courses (cyclophosphamide, epirubicin, 5-fluorouracil) to 15 patients, as FEC courses (5-fluorouracil, epirubicin, cyclophosphamide) to 5 patients. Patients were assessed and the size of the tumor was measured by mammography and ultrasonography before and at the end of the treatment. Due to the clinical results after the chemotherapy patients were assessed as complete and partial responders (34 patients), non-responders(4 patients) and progressinon of disease (2 patients). Results: Among non-responders patients T1/2 was significantly high (average value 159,8 min.) than among patients with complete answer to chemotherapy (average value of T1/2 122,1min). In 2 cases of BC progression showed a rapid tumour clearance of 99mTc MIBI - ≥ 113 min. Conclusions: The efflux rate of 99 mTc MIBI may be used for the in vivo identification of chemotherapy prediction to neoadjuvant chemotherapy in patients with locally advanced breast cancer. A rapid tumour clearance of 99mTc-MIBI may predict lack of tumour response to chemotherapy. 76 poster RESPONSE EVALUATION FOLLOWING CHEMORADIATION WITH NELFINAVIR IN PANCREATIC CARCINOMA – IS FDG-PET CT RELIABLE? M. Scott-Brown1 , A. Cavallaro2 , T. Brunner1 1 G RAY I NSTITUTE OF R ADIATION O NCOLOGY & B IOLOGY, U NIVERSITY OF OXFORD, Oxford, United Kingdom 2 U NIVERSITY H OSPITALS OF E RLANGEN, Radiology, Erlangen, Germany Purpose: Image based response assessment is difficult in locally advanced pancreatic cancer. In a phase I trial of chemoradiation with a signal transduction inhibitor, nelfinavir, that blocks Akt we correlated the CT and 18 FDG-PET CT response with pathological response. Preclinical work shows that nelfinavir additionally renormalizes tumour vascularisation and reduces hypoxia. These microenvironmental effects are persistent so they may be clinically useful in combination with radiation and or chemotherapy. However changes in the tumour microenvironment may impact on response assessment e.g. 18 FDG-PET CT may be less reliable.
Conclusions: CT, 18 FDG-PET CT and pathological response assessment strongly disagree. CT response systematically underestimates response due to desmoplastic reactions. On the other hand 18 FDG-PET CT may overestimate response when used with drugs impacting on the Akt pathway: these drugs may shut down the Warburg effect, result in a reduction of Glut-1 expression, and therefore reduce Glucose uptake. 18 FDG-PET CT imaging to assess response to treatment is therefore unreliable after treatment with these signal transduction inhibitors. We therefore require novel functional imaging modalities to assess response following treatment with these molecularly targeted agents. 77 poster STUDY OF THE FOLLOW UP OF SUV AND VOLUME MEASUREMENT OF 18FDG-PET POSITIVE TISSUES DURING RADIOTHERAPY K. Doyeux1 , A. Bak1 , A. Edet-Sanson1 , B. Dubray1 , S. Hapdey1 , D. Gensanne1 , P. VERA1 , I. Gardin1 1 LITIS (EA4108) ET C ENTRE H ENRI -B ECQUEREL, Rouen, France Purpose: To study the follow up of Standard Uptake Value (SUV) and volume (V) measurement of positive tissues in 18 FDG-PET imaging during radiotherapy (RT) of non-small cell lung cancer for predictive purpose. Materials: The total dose ranged between 60 to 70 Gy (2 Gy/d, 5 d/wk). Each patient (n=10), underwent 5 (n=5) to 6 PET/CT (n=5) 60+ /- 5 min after the injection of 3.5 MBq/kg of FDG (Siemens Biograph Sensation). All PET examinations consist in 2 thoracic acquisitions: ungated (3 min) and gated using a respiratory gated system (ANZAI, 15 min, 5 images/cycle). PET0 corresponded to a pre-treatment acquisition. PET 1 to 5 were acquired every 14 Gy covering the whole RT course. The studied parameters were the maximum SUV (SUVmax) in the lesion, and its volume, V, using 3 thresholding methods: a threshold of 40% (M40), a threshold defined visually, (MVi), a semi-automatic thresholding method, MTh (Vauclin et al. Phys Med Biol 2009). For the follow up analysis of each lesion, the parameters were normalized to 100 at PET0. A one sample analysis t-test with a 95% confidence interval was used to compare the mean SUV or V at PETn to 100 (PET0). Results: The follow up concerned 17 lesions corresponding to 93 positive tissues detected on PET images. No movement of lesions was observed on respiratory gated images and the measurements were carried out on the ungated data.The whole 93 SUVmax could be measured (range: 1.2 to 18.2), even for very low ones (SUV < 2), due to the follow up context. Only 77 positive tissues could be segmented by MVi (0.2 mL to 70.6 mL) vs. 75 for MTh and M40. Due to the decrease of the SUV over the time, V40 tends to increase during RT. The mean normalized volume (± 1 Std Dev) was V40(PET4) = 226 ± 198 (p=0.076, n=10 lesions), whereas the mean Vth remains stable with no statistical difference between PET4 and PET0
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73 poster MOLECULAR REMISSION AFTER NEOADJUVANT CHEMORADIATION IN MEDIASTINAL LYMPH NODE METASTASES AS DETECTED BY F-18 FDG PET IN PATIENTS WITH NSCLC V. Prasad1 , M. Schmuecking2 , R. P. Baum1 , C. P. Schneider3 , N. Presselt4 , J. Leonhardi5 , K. Hoeffken6 , K. M. Mueller7 , T. Wendt8 , R. Bonnet3 1 Z ENTRALKLINIK B AD B ERKA, Department of Nuclear Medicine / Center for P.E.T., Bad Berka, Germany 2 G REIZ C OUNTY H OSPITAL, Center for Radiology, Greiz, Germany 3 Z ENTRALKLINIK B AD B ERKA, Department of Pneumology, Bad Berka, Germany 4 Z ENTRALKLINIK B AD B ERKA, Department of Thoracic Surgery, Bad Berka, Germany 5 Z ENTRALKLINIK B AD B ERKA, Department of Radiology, Bad Berka, Germany 6 U NIVERSITY HOSPITAL J ENA, Department of Hematology / Oncology, Jena, Germany 7 U NIVERSITY H OSPITAL B ERGMANNSHEIL, Department of Pathology, Bochum, Germany 8 U NIVERSITY HOSPITAL J ENA, Department of Radiation Oncology, Jena, Germany
72 poster MOLECULAR IMAGING OF RADIATION RESPONSE IN PRECLINICAL MODELS USING A NOVEL SMALL ANIMAL RADIOTHERAPY SYSTEM G. Nelson1 , M. Vilalta2 , J. Pérez1 , M. Bazalova1 , A. Giaccia2 , E. Graves3 1 S TANFORD U NIVERSITY S CHOOL OF M EDICINE, Radiation Physics, Stanford, USA 2 S TANFORD U NIVERSITY S CHOOL OF M EDICINE, Division of Radiation Oncology , Stanford, USA 3 S TANFORD C ANCER C ENTER, Raditaion Oncoloy, Stanford, USA Purpose: Typical small animal irradiation methods are incapable of the spatial accuracy routinely achieved in a modern cancer center. To mitigate this, a microCT system was modified to produce a clinically similar system for small animal image-guided conformal radiotherapy. By collimating the x-ray beam from the microCT, beams as small as 1 mm at isocenter can be delivered to anesthetized subjects. Combined with a custom bed capable of 3D movement, arbitrary targets within a mouse can be imaged, localized, targeted, and irradiated. Application of this technology to mouse models of disease allows for exploration of functional imaging in radiotherapy using preclinical molecular imaging. The biological response of tissues to emerging radioand chemotherapies have been evaluated with γ H2AX immunohistochemistry, positron emission tomography (PET) with the tracers fluorodeoxyglucose (FDG), fluorothymidine (FLT), fluoroazomycin arabinoside (FAZA), and bioluminescence imaging (BLI). Materials: We evaluated the ability of the system to induce a biological response in a small target by conformally irradiating a spontaneous murine model of lung cancer. Immediately after treatment the mice were sacrificed and the tumors were excised, sectioned, and stained for γ H2AX stained to evaluate DNA double strand breaks. We investigated the effect of treatment on normal and neoplastic tissue by performing BLI and FDG and FLT PET scans before and after treatment to a variety of radiation doses to establish the dose response. Finally, the utility of combined radiotherapy and anti-HIF-1 chemotherapy was evaluated using BLI and FAZA PET. Results: The system is capable of accurate dose delivery. It is able to deliver dose to targeted areas while sparing others using radiation delivery techniques analogous to those commonly employed in the clinic. Dose fractionation is feasible and allows the system to deliver a greater total dose. Dose response of tissues was evident from serial BLI of tumors treated with radiation. Molecular imaging of therapeutic responses varied greatly between molecular targets and tumor types and encourages further study of the potential role of these imaging modalities in clinical radiation oncology. Conclusions: A system for clinically-relevant small animal image-guided conformal radiotherapy has been constructed, validated, and employed to investigate molecular imaging of radiation response using a variety of modalities.
Purpose: To evaluate the role of molecular remission in mediastinal lymph node metastases after neoadjuvant chemoradiation as detected by 18F FDG PET/CT, findings in 32 patients with NSCLC stage III were analyzed prospectively. Materials: Inclusion criteria: histologically confirmed NSCLC stage IIIA/IIIB. ECOG PS 0-1, adequate hematologic, renal, hepatic function. Primary end points: OS, DFS. Secondary end points: TTP, QoL, RR. Neoadjuvant treatment: 2-3 cycles of paclitaxel/carboplatin and a block of chemoradiation (45Gy, 1.5Gy b.i.d., concomitant paclitaxel/carboplatin) followed by surgery. Randomization: late (Arm1) vs. early (Arm2) chemoradiation. Staging: PET in addition to CT and/or MRI after randomization, second PET after completion of neoadjuvant therapy prior to surgery. Assessment of standardized uptake values (SUV) in primary tumor (PT) and all metastatic lymph nodes (LN). Documentation of involved LN as detected by PET and LN sampling during surgery according to Naruke/ATS-LCSG classification. Evaluation of histological regression grade (RG) and correlation with PET for PT and each LN. Molecular radiation treatment planning (MRTP) using fused PET/CT data. Evaluation of ’out-field’ and ’in-field’ recurrences after PET planned radiation treatment by follow-up studies using PET/CT, CT and MRI). Intent to treat analyses using Kaplan-Meier estimates, log rank tests and Cox multivariate models. Results: So far 32/210 eligible pts were analyzed (192 lymph node regions, 576 lymph nodes). Actuarial tumor specific survival: complete vs. incomplete metabolic remission after 60 months: 43% vs. 24% (p = .018), RG III/IIb (no/less than 10% of vital tumor cells) vs. RG IIa/I (more than 10% vital tumor cells) after 60 months: 46% vs. 18% (p < .006). So far, follow-up studies showed no mediastinal ’out-field’ recurrences in mediastinal lymph nodes which received no radiation treatment. ’In-field’ recurrences were observed in 11/32 pts, 7/11 pts had initially an incomplete remission after neoadjuvant chemoradiation. Conclusions: Molecular remission in mediastinal lymph nodes as detected by 18F-FDG PET correlates well with RG and may predict (long-term) therapeutic outcome in pts with stage III NSCLC. 18F-FDG PET precedes CT in measuring the tumor response. Integration of PET in clinical trials enables a more accurate therapy management. Our preliminary data of 32 pts suggest that an elective nodal irradiation (ENI) of inconspicuous lymph nodes as detected by PET may not be necessary for NSCLC stage III. 74 poster PET SCAN GUIDED INTERSTITIAL BRACHYTHERAPY IN CERVICAL CANCER PATIENTS WITH CLINICALLY SUSPECTED RESIDUAL DISEASE D. N. Sharma1 , G. K. Rath1 , S. Kumar2 , R. Kumar3 , P. K. Julka1 , P. Jagadesan1 , V. Subramani1 1 A LL I NDIA I NSTITUTE OF M EDICAL S CIENCES, Radiation Oncology, NewDelhi, India 2 A LL I NDIA I NSTITUTE OF M EDICAL S CIENCES, Gynaecology, NewDelhi, India 3 A LL I NDIA I NSTITUTE OF M EDICAL S CIENCES, Nuclear Medicine, NewDelhi, India Purpose: To evaluate the role of PET Scan guided consolidation interstitial brachytherapy (IBT) in cervical carcinoma patients with clinically suspected residual disease after 4 weeks of completion of concurrent chemoradiotherapy (CCRT). Materials: During the year 2006-2007, 23 cervical carcinoma patients having clinically suspected residual disease showing FDG uptake in the cervical/ para cervical region after 4 weeks of completion of the standard course of CCRT were enrolled into the study. Patients with clinically evident or frank residual disease were excluded from this study. Before consolidation IBT,
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the standard CCRT consisted of whole pelvis EBRT with 40 Gy in 22fractions over 4.5 weeks followed by 10 Gy in 5fractions over 1 week with midline shielding and then 3 sessions of weekly HDR intracavitary brachytherapy of 7 Gy each to Point A. Weekly chemotherapy (Cisplatin, 40 mg/sqm) was administered during the course of EBRT to all patients. Four weeks later, PET/CT Scan was done on dedicated PET-CT scanner (SIEMENS, BIOGRAPH 64) using 5-10 mCi of intravenous FDG. The consolidation therapy consisted of a single session of high dose rate (HDR) IBT with a dose of 8-10 Gy. IBT needles were inserted through the perineum using Martinez Universal Perineal Interstitial Template under the guidance of Trans-rectal ultrasound (TRUS). Treatment planning was done on Nucletron planning system (PLATO) using the CT Scan images. IBT treatment was carried out on Microselectron HDR remote after loading unit and the perineal template was removed immediately after completing the treatment. All patients were followed up monthly till 6 months, every 2 months till 1 year and then every 3-6 months thereafter. Results: Follow up period ranged from 3-18 months (median 11 months). Of 23 patients, 15 (65%) had pelvic disease control, 6 had pelvic failure, 1 had para-aortic node recurrence and 1 lung metastases. One patient had hematuria during postoperative period, which stopped after 24 hours. Overall late toxicity (grade III-IV) was noticed in 3 (13%) patients. Of them, 2 had recto-vaginal fistula and 1 had sub acute intestinal obstruction. Conclusions: In patients with cervical carcinoma having residual disease on PET scan after 4 weeks of completion of CCRT, consolidation treatment with single fraction of 8 Gy HDR IBT provides effective pelvic control rate and acceptable complication rate. It may be further studied with a larger sample size.
Materials: In a Phase I trial, 10 patients completed therapy with nelfinavir (1250mg bd D-2 to 45) and chemoradiation (Phase I 50.4Gy in 28#, Phase II 9.0Gy in 5# (D1 to 45) with concomitant Cisplatin 30mg/m2 + Gemcitabine 200mg/m2 (DL1) 300mg/m2 (DL2) D1, 8, 22, 29) for locally advanced pancreatic cancer. Response to treatment was evaluated with CT (RECIST criteria) and 18 FDG-PET CT (change in SUV) six weeks following completion of chemoradiotherapy and correlated with the pathological specimen in the 6 patients who underwent resection (all R0). Results: In the five evaluable resected patients with pre- and post-therapeutic 18 FDG-PET CT imaging the responses on 18 FDG-PET CT were superior to the responses on CT, however neither CT nor 18 FDG-PET CT were accurate predictors of pathological response. 18 FDG-PET CT showed a CR in four patients, three of whom had residual viable tumour on pathological examination (<10% viable tumour in two patients, but one patient had a ypT3N1 tumour with 50-80% viable tumour cells), and one patient who had a pCR.
75 poster RADIONUCLIDE EVALUATION OF RESPONSE TO NEOADJUVANT CHEMOTHERAPY IN BREAST CANCER PATIENTS O. Solodyannikova1 1
U KRAINIAN R ES .I NST. OF O NCOL ., Department of Nuclear Medicine, Kiev, Ukraine
Purpose: Searching of most informative and clinical based methods of estimation and prediction of chemotherapy treatment and monitoring among breast cancer (BC) patients is very acute medical problem, limiting advanced breast cancer treatment. The aim of present study was to evaluate whether tuomour clearance of 99mTc MIBI is capble to assess tumour response to neoadjuvant chemotherapy in patients with locally advanced BC. Materials: 40 BC patients planning for undergoing neoadjuvant chemotherapy were investigated 2-8 days prior to chemotherapy using scintimammography (SMG) with 99mTc- MIBI. Static scintimammography was performed 10 and 60 min. post intravenous injection of 400-550 MBq of 99mTc-MIBI. Time to half clearance (T1/2) of 99mTc MIBI was calculated in each patient from decay-corrected time-activity curves using monoexponential fitting. Chemotherapy was given as either standard AC courses (doxorubicin, cyclophosphamide) to 20 patients, as CEF courses (cyclophosphamide, epirubicin, 5-fluorouracil) to 15 patients, as FEC courses (5-fluorouracil, epirubicin, cyclophosphamide) to 5 patients. Patients were assessed and the size of the tumor was measured by mammography and ultrasonography before and at the end of the treatment. Due to the clinical results after the chemotherapy patients were assessed as complete and partial responders (34 patients), non-responders(4 patients) and progressinon of disease (2 patients). Results: Among non-responders patients T1/2 was significantly high (average value 159,8 min.) than among patients with complete answer to chemotherapy (average value of T1/2 122,1min). In 2 cases of BC progression showed a rapid tumour clearance of 99mTc MIBI - ≥ 113 min. Conclusions: The efflux rate of 99 mTc MIBI may be used for the in vivo identification of chemotherapy prediction to neoadjuvant chemotherapy in patients with locally advanced breast cancer. A rapid tumour clearance of 99mTc-MIBI may predict lack of tumour response to chemotherapy. 76 poster RESPONSE EVALUATION FOLLOWING CHEMORADIATION WITH NELFINAVIR IN PANCREATIC CARCINOMA – IS FDG-PET CT RELIABLE? M. Scott-Brown1 , A. Cavallaro2 , T. Brunner1 1 G RAY I NSTITUTE OF R ADIATION O NCOLOGY & B IOLOGY, U NIVERSITY OF OXFORD, Oxford, United Kingdom 2 U NIVERSITY H OSPITALS OF E RLANGEN, Radiology, Erlangen, Germany Purpose: Image based response assessment is difficult in locally advanced pancreatic cancer. In a phase I trial of chemoradiation with a signal transduction inhibitor, nelfinavir, that blocks Akt we correlated the CT and 18 FDG-PET CT response with pathological response. Preclinical work shows that nelfinavir additionally renormalizes tumour vascularisation and reduces hypoxia. These microenvironmental effects are persistent so they may be clinically useful in combination with radiation and or chemotherapy. However changes in the tumour microenvironment may impact on response assessment e.g. 18 FDG-PET CT may be less reliable.
Conclusions: CT, 18 FDG-PET CT and pathological response assessment strongly disagree. CT response systematically underestimates response due to desmoplastic reactions. On the other hand 18 FDG-PET CT may overestimate response when used with drugs impacting on the Akt pathway: these drugs may shut down the Warburg effect, result in a reduction of Glut-1 expression, and therefore reduce Glucose uptake. 18 FDG-PET CT imaging to assess response to treatment is therefore unreliable after treatment with these signal transduction inhibitors. We therefore require novel functional imaging modalities to assess response following treatment with these molecularly targeted agents. 77 poster STUDY OF THE FOLLOW UP OF SUV AND VOLUME MEASUREMENT OF 18FDG-PET POSITIVE TISSUES DURING RADIOTHERAPY K. Doyeux1 , A. Bak1 , A. Edet-Sanson1 , B. Dubray1 , S. Hapdey1 , D. Gensanne1 , P. VERA1 , I. Gardin1 1 LITIS (EA4108) ET C ENTRE H ENRI -B ECQUEREL, Rouen, France Purpose: To study the follow up of Standard Uptake Value (SUV) and volume (V) measurement of positive tissues in 18 FDG-PET imaging during radiotherapy (RT) of non-small cell lung cancer for predictive purpose. Materials: The total dose ranged between 60 to 70 Gy (2 Gy/d, 5 d/wk). Each patient (n=10), underwent 5 (n=5) to 6 PET/CT (n=5) 60+ /- 5 min after the injection of 3.5 MBq/kg of FDG (Siemens Biograph Sensation). All PET examinations consist in 2 thoracic acquisitions: ungated (3 min) and gated using a respiratory gated system (ANZAI, 15 min, 5 images/cycle). PET0 corresponded to a pre-treatment acquisition. PET 1 to 5 were acquired every 14 Gy covering the whole RT course. The studied parameters were the maximum SUV (SUVmax) in the lesion, and its volume, V, using 3 thresholding methods: a threshold of 40% (M40), a threshold defined visually, (MVi), a semi-automatic thresholding method, MTh (Vauclin et al. Phys Med Biol 2009). For the follow up analysis of each lesion, the parameters were normalized to 100 at PET0. A one sample analysis t-test with a 95% confidence interval was used to compare the mean SUV or V at PETn to 100 (PET0). Results: The follow up concerned 17 lesions corresponding to 93 positive tissues detected on PET images. No movement of lesions was observed on respiratory gated images and the measurements were carried out on the ungated data.The whole 93 SUVmax could be measured (range: 1.2 to 18.2), even for very low ones (SUV < 2), due to the follow up context. Only 77 positive tissues could be segmented by MVi (0.2 mL to 70.6 mL) vs. 75 for MTh and M40. Due to the decrease of the SUV over the time, V40 tends to increase during RT. The mean normalized volume (± 1 Std Dev) was V40(PET4) = 226 ± 198 (p=0.076, n=10 lesions), whereas the mean Vth remains stable with no statistical difference between PET4 and PET0