Sarcopenia is Associated with Chemotherapy Toxicity in Patients Undergoing Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis from Colorectal Cancer.

BACKGROUND: Despite the positive survival results of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), criticisms have been put forward regarding the safety of this treatment as a result of a high morbidity rate. Muscle depletion (sarcopenia) is associated with the occurrence of postoperative complications. The purpose of this study was to determine the association between sarcopenia and postoperative morbidity after CRS-HIPEC for peritoneal carcinomatosis from colorectal cancer by distinguishing the complications linked to CRS itself and those associated with chemotherapy (HIPEC) toxicities. METHODS: Data concerning 97 consecutive patients who had undergone CRS-HIPEC were recorded. We analyzed the events occurring within 30 days after surgery that were prospectively recorded in a database. Sarcopenia was assessed using the L3 muscle index on computed tomography performed during the 2 months preceding surgery. RESULTS: The sarcopenic patients experienced significantly more chemotherapy toxicities (57 vs. 26 %; p = 0.004) and especially neutropenia (36 vs. 17 %; p = 0.04) than their nonsarcopenic counterparts. There was no difference in complications linked to the CRS procedure between sarcopenic and nonsarcopenic patients. In the multivariate analysis, sarcopenia was the only parameter independently associated with the risk of chemotherapy toxicity (odds ratio 3.97; 95 % confidence interval 1.52-10.39; p = 0.005). CONCLUSIONS: Despite the local administration of chemotherapy, systemic toxicity was observed in sarcopenic patients after CRS-HIPEC. This relationship favors new treatment strategies with white blood cell growth factors or chemotherapy dosing based on muscle value.

[Impact of cancer muscle mass loss on anticancer treatment toxicities]. / Conséquences de la diminution de la masse musculaire sur la tolérance des traitements anticancéreux.

Administration of targeted therapies as a flat dose and administration of chemotherapy based on body surface area do not take into account several important sources of inter-individual variation. These variations could be responsible partially for the occurrence of toxicity. Furthermore, the availability of high-resolution CT images in the record of cancer patients, from which key body composition information may be derived, allows us to study the relationship between body composition and toxicity. If many studies have highlighted this relationship, the mechanisms are not completely understood. There are some arguments for a pharmacokinetic hypothesis: low muscle mass i.e. sarcopenia, is associated with high drug plasma concentration which in turn is associated with an increase in the incidence of toxicity. The other hypothesis is that sarcopenic patients have a higher susceptibility to medical events leading to an increase in chemotherapy toxicity. This concept of frailty was widely described in studies in the elderly. This body composition analysis opened a huge area of research and many questions still need to be resolved. Defining the cut-offs values for low muscle mass is important since in most of the studies, the cut-offs values used were defined using survival studies. What could be the physiological link between cut-off values defined by survival studies and chemotherapy toxicities? Authors also used the median values, the level which predicted the occurrence of toxicity most accurately and sometimes the measure of the psoas. The final and crucial question is the capacity of reducing toxicity by body composition based dosing.

Extended 21-sample needle biopsy protocol for diagnosis of prostate cancer in 1000 consecutive patients.

OBJECTIVE: To prospectively evaluate the diagnostic yield of a 21-sample ultrasound-guided needle biopsy protocol as the initial diagnostic strategy for detection of prostate cancer. MATERIALS AND METHODS: Between December 2001 and October 2005, 1000 consecutive patients underwent 21-sample needle biopsies under local anesthesia, comprising sextant biopsies, 3 additional posterolateral biopsies in each peripheral zone, 3 biopsies in each transition zone (TZ), and 3 biopsies in the midline peripheral zone. Each prostate core was numbered and analyzed separately. The patients were divided into subgroups according to the result of digital rectal examination (DRE), serum prostate-specific antigen (PSA), and prostate volume. We evaluated the cancer detection rate overall and in each subgroup. We compared the results of our biopsy protocol to those from 6-, 12-, and 18-core biopsy protocols by analyzing only those cores from our protocol that would correspond to these biopsy schemes. RESULTS: Cancer detection rates using 6 biopsy samples (sextant biopsies only), 12 samples (sextant plus lateral biopsies), 18 samples (sextant, lateral, and TZ biopsies), and 21 samples (sextant, lateral, TZ, plus midline biopsies) were 31.7%, 38.7%, 41.5%, and 42.5%, respectively. The 12-sample procedure improved the cancer detection rate by 22% compared with the 6-sample procedure (p=0.0001). The improvement in the diagnostic yield was most marked in patients with a prostate volume > or =55 ml (36.9%), in patients with normal DRE (26.6%), and in patients with PSA<4 (37.5%). The addition of TZ biopsies to a 12-biopsy scheme increased the diagnostic yield by 7.2% overall (p=0.023). Only 10 of 425 (2.3%) patients were diagnosed on the sole basis of midline biopsies. CONCLUSIONS: Patients with suspected localized prostate cancer should be offered at least 12 biopsies in the peripheral zone and far lateral peripheral zone (statistically significant). TZ biopsies have to be considered, because these biopsies improve the diagnostic yield. For patients with abnormal DRE and/or PSA> or =20 ng/ml, the 6-biopsy scheme seems sufficient (statistically), but 6 far lateral peripheral zone biopsies as well as the TZ biopsies add little incremental value (not significant). Evidence does not support the use of routine midline peripheral zone needle biopsies in the initial biopsy to enhance the detection of prostate cancer.

Saturation biopsy protocol enhances prediction of pT3 and surgical margin status on prostatectomy specimen.

A 21-samples saturation biopsy procedure (SBP) was developed in order to improve prostate cancer detection rate. Out of 650 patients who underwent this protocol, 150 had a clinically localized prostate cancer and underwent a radical prostatectomy. The number of cores positive for tumor was assessed in the SBP, and also in the sextant component of the SBP (SC) and in the non-sextant component of the SBP (NSC). Numbers of cores positive for tumor on SBP, SC, and NSC were significantly higher in pT3 group versus pT2 (P < 0.001 each) and in positive surgical margins (PSM) group versus no PSM (P < 0.001 each). When comparing area under the curve obtained from SBP with those obtained from NSC and SC, the SBP showed higher accuracy than the NSC and the SC for the prediction of pT3 and PSM. On multivariate analyses, SC and NSC were independent predictors of pT3 and PSM on radical prostatectomy.