Operational classification of cutaneous squamous cell carcinomas based on unsupervised clustering of real cases by experts.

BACKGROUND: There is currently no staging system for cutaneous squamous cell carcinoma (cSCC) that is adapted to decision-making and universally used. Experts have unconscious ability to simplify the heterogeneity of clinical situations into a few relevant groups to drive their therapeutic decisions. Therefore, we have used unsupervised clustering of real cases by experts to generate an operational classification of cSCCs, an approach that was successful for basal cell carcinomas. OBJECTIVE: To generate a consensual and operational classification of cSCCs. METHOD: Unsupervised independent clustering of 248 cases of cSCCs considered difficult-to-treat. Eighteen international experts from different specialties classified these cases into what they considered homogeneous clusters useful for management, each with freedom regarding clustering criteria. Convergences and divergences between clustering were analysed using a similarity matrix, the K-mean approach and the average silhouette method. Mathematical modelling was used to look for the best consensual clustering. The operability of the derived classification was validated on 23 new practitioners. RESULTS: Despite the high heterogeneity of the clinical cases, a mathematical consensus was observed. It was best represented by a partition into five clusters, which appeared a posteriori to describe different clinical scenarios. Applicability of this classification was shown by a good concordance (94%) in the allocation of cases between the new practitioners and the 18 experts. An additional group of easy-to-treat cSCC was included, resulting in a six-group final classification: easy-to-treat/complex to treat due to tumour and/or patient characteristics/multiple/locally advanced/regional disease/visceral metastases. CONCLUSION: Given the methodology based on the convergence of unguided intuitive clustering of cases by experts, this new classification is relevant for clinical practice. It does not compete with staging systems, but they may complement each other, whether the objective is to select the best therapeutic approach in tumour boards or to design homogeneous groups for trials.

Ultrahypofractionated CyberKnifeTM based stereotactic radiotherapy versus conventional radiotherapy in patients with prostate cancer - acute toxicity evaluation in two phase II prospective studies.

Our purpose was to compare the acute toxicity of ultrahypofractionated CyberKnifeTM based stereotactic radiotherapy (SBRT Arm) and conventional radiotherapy (EBRT Arm) in prostate cancer patients. Two-hundred-sixteen men with prostate cancer were enrolled in our prospective studies. One-hundred and nine were irradiated using CyberKnife to total dose of 36,25 Gy in 5 fractions. One-hundred and seven were irradiated conventionally to total dose of 76 Gy in 38 fractions. Mean age of patients was 69. Acute genitourinary (GU) and gastrointestinal (GI) adverse-events were collected. The maximal acute toxicity EORTC/RTOG score was assumed. A total of 41%, 44%, 12% and 3% of patients presented grade 0, 1, 2 and 3 acute genitourinary toxicity in SBRT arm, respectively. A total of 21%, 33%, 43% and 3% of patients demonstrated acute grade 0, 1, 2 and 3 genitourinary toxicity in EBRT arm. A significant difference between number of patients with grade 2 GU toxicity was observed (p-0.000) and between patients without any toxicity (p-0.0017).A significant difference in frequency of acute GI toxicity between both groups was observed, too. 71% vs. 44% had no toxicity (p-0.0001), and 3% vs. 18% (p-0.0004) presented grade 2 GI toxicity in SBRT and EBRT arms respectively.The acute toxicity rates of fractionated stereotactic radiotherapy is lower compared to conventional irradiation.

Daily image-guidance in prostate cancer radiotherapy - implications for treatment margins.

UNLABELLED: Our purpose was to evaluate interfractional organ and patient movement during radiotherapy of prostate cancer and to calculate the necessary CTV to PTV margins. Fifty patients irradiated between 2009 and 2011were included into the prospective study. The 2D-2D KV system combined with the intraprostatic fiducial marker were used for daily position verification. Based on the 8629 measurements of isocentre displacement an interfractional motion of pelvis and prostate was evaluated. The CTV to PTV margins were calculated. Margins of 0.7 cm (AP), 1 cm (SI) and 0.35 cm (LR) are necessary when only bony based IGRT is performed. Margins of 1.0 cm, 1.8 cm and 0.5 cm in AP, SI and LR directions respectively are necessary in case of no IGRT.There was no clinically relevant changes in patient/target mobility throughout the whole treatment. The IGRT is essential for state of art radiotherapy of prostate cancer. Necessary CTV to PTV margins are much bigger in case of no IGRT performed. Changing of margins size throughout regular treatment is not necessary. KEYWORDS: IGRT, prostate cancer, fiducial marker.

Acute toxicity of robotic ultrahypofractionated radiotherapy CyberKnifeTM in prostate cancer patients.

Our purpose was to evaluate the toxicity of CyberKnifeTM based fractionated stereotactic radiotherapy (FSRT) in prostate cancer patients. One-hunred-thirty-two men with low (62) and intermediate (70) prostate cancer were enrolled in our prospective study. Mean age was 69. Total dose of 36,25 Gy in 5 fractions was prescribed. Image guided FSRT was performed on CyberKnife. Minimum follow-up ranged from 3 to 28 months. EORTC/RTOG scale was used to evaluate toxicity. A total of 47%, 10% and 2% of patients presented grade 1, 2 and 3 acute genitourinary toxicity, respectively. In 25% and 3% of patients, respectively, grade 1 and 2 acute gastrointestinal toxicity was observed. No significant association between acute grade ≥ 2 toxicity and clinical factors: age, androgen deprivation therapy or infections were found. Neither CTV nor PTV volumes had significant impact on acute grade ≥ 2 toxicity. Late toxicity was assessed in 104 patients. In 16% and 1% of patients late GU toxicity in grade 1 and 2, respectively, was presented. Late GI toxicity grade 1, 2 and 3 occurred in 8%, 3% and 1% of patients, respectively. The acute toxicity rates of fractionated stereotactic radiotherapy are low. Early data suggest also low late toxicity rates.