A TCP-based early regression index predicts the pathological response in neo-adjuvant radio-chemotherapy of rectal cancer.

PURPOSE: Introducing a radiobiological index based on early tumor regression during neo-adjuvant radio-chemotherapy (RCT, including oxaliplatin) of rectal adenocarcinoma and testing its discriminative power in predicting the tumor response. METHODS: Seventy-four patients were treated with Helical Tomotherapy following an adaptive (ART) protocol (41.4 Gy/18 fr, 2.3 Gy/fr) delivering a simultaneous integrated boost on the residual tumor in the last 6 fractions up to 45.6 Gy. T2-weighted MRI were taken before (MRIpre) and at mid (MRImid) therapy and the corresponding tumor volumes were considered (Vpre,Vmid). The "Early Regression Index" [Formula: see text] was introduced and its discriminative power was assessed in terms of AUC, sensitivity/specificity, positive/negative predictive value (PPV/NPV). Two end-points were considered: (a) pathological complete response (pCR) or clinical complete response followed by watch-and-wait, (cCR); (b) limited response (residual vital cells (RVC) in the surgical specimen >10%). RESULTS: Complete data were available for 65 patients: pCR, cCR and RVC >10% were 20, 2 and 19 respectively. The discriminative power of ERITCP was moderately high (AUC = 0.81/0.75 for /pCRorcCR/RVC >10% respectively, p < 0.0005). ERITCP was highly sensitive (86-89%) with very high NPV (90-94%). The discriminative power of ERITCP was confirmed on a subgroup of 44/65 patients when considering tumor volumes delineated by a skilled radiologist. CONCLUSION: A radiobiologically consistent index based on early regression showed high performances in predicting the pathological response after neo-adjuvant RCT for rectal cancer with relevant potentialities for ART/treatment customization.

Early volume variation of positive lymph nodes assessed by in-room mega voltage CT images predicts risk of loco-regional relapses in head and neck cancer patients treated with intensity-modulated radiotherapy.

BACKGROUND: We investigated the possibility to early identify non-responding patients based on FDG-PET positive lymph nodes (PNs) volume variation assessed with in-room images. MATERIAL AND METHODS: Twenty-seven head and neck cancer patients with at least one pre-treatment PNs were retrospectively analyzed; they received 54 Gy, 66 Gy, 69 Gy in 30 fractions on precautionary lymph nodal (N), primary (T) and PET positive (BTV) planning target volumes (PTVs), respectively with Helical TomoTherapy (SIB approach). PNs volume changes during treatment were assessed based on megavoltage computed tomography (MVCT) used for image guidance as ratio between volumes at fractions 10/20/30 and at first fraction. Data on T, N and M relapses (rT, rN, rM) were collected for all patients. The difference of PNs volume changes, during treatment, between patients with versus without relapses was tested (Mann-Whitney test). The impact of shrinkage on the corresponding survival curves (Cox proportional-hazard regression), dividing between no/moderate versus large shrinkage (based on ROC curve best cut-off value) was also investigated. RESULTS: Median follow-up was 27.4 m (3.7-108.9). The numbers for rT, rN, rM were 5, 4, 6, respectively. Differences in PNs shrinkage were found between patients with and without rT/rN at all considered timing [fr 20, rT: 0.56 vs. 1.07 (median), p = 0.06; rN: 0.57 vs. 1.25, p = 0.07]. Differences were lower for rM. Survival curves provide high hazard ratios (HR) between PNs changes and rT/rN at all considered timing [fr 20, rT: best cut-off = 0.58, HR 5.1 (95% CI 0.5-49.4), p = 0.12; rN: best cut-off = 0.98, HR 14.9 (1.6-142.9), p = 0.01]. CONCLUSION: A limited shrinkage of PNs during treatment is associated with poorer outcome in terms of T/N relapses. The early variation of PNs observed on in-room images may provide useful information about the individual response with potential application in guiding an early adaptation of the treatment.

Characterization of volume and shape modifications of PET-positive nodes during Tomotherapy for head and neck cancer as assessed by MVCTs.

PURPOSE: Characterizing the changes of PET-positive lymphnodes (PNs) of head-neck cancer patients during image-guided Tomotherapy in order to verify if our clinical margin for PTV(boost) are adequate. MATERIAL AND METHODS: Weekly MVCTs of 30 patients were matched with the planning kVCT (kVCT_pl) on bony anatomy: 42 visible PNs were contoured on kVCT_pl/MVCTs. Intra/inter-observer and inter-modality variability in contouring PNs was evaluated by blind re-delineation. Shrinkage of PNs and center-of-mass (CM) shifts were measured and Van Herk margins for the residual error were estimated. In addition, due to the PNs' shrinkage during therapy, probability coverage maps were considered to estimate the fraction of the high probability contours missed by the clinical PTV (5 mm margin); larger margins were tried for PNs showing some missing. RESULTS: MVCTs were adequate for PNs' delineation (DICE=0.85; range=0.79-0.91). Twenty-seven PNs showed a significant volume shrinkage at the end of therapy (median: 71%, range: 27-94%, ρ=-0.93). Time-trend of 3D-CM shift was significant for 38% of PNs (median: 5.1 mm at the end of treatment, range: 1.0-8.9). The clinical PTV included 95% of the 90%/100% probability contours in 40/36 (95%/86%) PNs respectively. Van Herk margins (not considering shrinkage) were approximately 7 mm for all three main axes. The clinical PTV included 95% of the 90%/100% probability contours in 40/36 (95%/86%) PNs respectively. CONCLUSIONS: The residual error relative to PNs after bone match is relatively small; the impact of CM shifts is partially counterbalanced by shrinkage. Our results do not seem to support an extensive use of adaptive re-planning to avoid the missing of PNs in dose-escalated protocols, although more information about the dosimetry impact of the reported changes is warranted.

Assessment and clinical validation of margins for adaptive simultaneous integrated boost in neo-adjuvant radiochemotherapy for rectal cancer.

PURPOSE: An adaptive concomitant boost (ACB) for the neo-adjuvant treatment of rectal cancer was clinically implemented. In this study population margins M(90,90) considering rectal deformation were derived for 10 consecutive patients treated at 18 × 2.3Gy with Helical Tomotherapy (HT) and prospectively validated on 20 additional patients treated with HT, delivering ACB in the last 6 fractions. METHODS: Sectorial margins M(90,90) of the whole and second treatment parts were assessed for 90% population through a method combining the 90% coverage probability maps of rectal positions (CPC90%) with 3D local distance measurements between the CPC90% and a reference rectal contour. M(90,90) were compared with the margins M(90,90)(95%/99%), ensuring CPC90% coverage with 95%/99% confidence level. M(90,90) of the treatment second part were chosen as ACB margins which were clinically validated for each patient by means of %volume missing of CPC5/6 excluded by the ACB margins. RESULTS: The whole treatment M(90,90) ranged between 1.9 mm and 9 mm in the lower-posterior and upper-anterior sectors, respectively. Regarding ACB, M(90,90) were 7 mm in the anterior direction and <5 mm elsewhere. M(90,90)(95%/99%) did not significantly differ from M(90,90). The %volume excluded by the ACB margin was<2% for all male and <5% for 9/10 female patients. The dosimetry impact on R_adapt for the patients with the largest residual error was negligible. CONCLUSIONS: Local deformation measurements confirm an anisotropic motion of rectum once set-up error is rigidly corrected. Margins of 7 mm anterior and 5 mm elsewhere are adequate for ACB. Female patients show a slightly larger residual error.