Assessment of tumor response to neoadjuvant chemotherapy in patients with breast cancer using MRI and FDG-PET/CT-RECIST 1.1 vs. PERCIST 1.0.

Therapeutic response to neoadjuvant chemotherapy (NAC) for breast cancer based on Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0 with FDG-PET/CT measurements was evaluated, and the results compared to those obtained with currently widely used Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, based on MRI measurements. MRI and FDG-PET/CT examinations were performed in 32 breast cancer patients before and after the NAC prior to a surgical resection. Chemotherapeutic response of the primary tumor and relapse-free survival (RFS) were investigated using RECIST 1.1 and PERCIST 1.0. Pathological complete response (pCR) was seen in 14 (43.8%) patients, while complete response (CR) was noted in 5, partial response in 25, stable disease in 2, and progressive disease in 0 with RECIST 1.1, and in 28, 2, 1, and 1, respectively, with PERCIST 1.0. For pCR prediction, the sensitivity, specificity, and accuracy with RECIST 1.1 were 28.6% (4/14), 94.4% (17/18), and 65.6% (21/32), and those with PERCIST 1.0 were 100% (14/14), 22.2% (4/18), and 56.3% (18/32). Five patients (15.6%) had recurrent development after a median period of 24 months (range 7.8-66.8 months). Patients who achieved CR shown by RECIST 1.1 showed slightly longer RFS than those who did not (p=0.46), whereas those with complete metabolic response (CMR) based on PERCIST 1.0 showed a relatively longer RFS than non-CMR patients (p=0.087). For prediction of pathological response to NAC in breast cancer, RECIST 1.1 and PERCIST 1.0 have complementary functions, however, FDG-PET as a post-NAC treatment assessment modality remains to be confirmed.

Diagnostic Performance of 11C-choline PET/CT and FDG PET/CT in Prostate Cancer.

We compared 11C-choline and FDG PET/CT scan findings for the staging and restaging of prostate cancer. Twenty Japanese prostate cancer patients underwent 11C-choline and FDG PET/CT before (n=5) or after (n=15) treatment. Using a five-point scale, we compared these scanning modalities regarding patient- and lesion-based diagnostic performance for local recurrence, untreated primary tumor, and lymph node and bony metastases. Of the 20 patients, documented local lesions, and node and bony metastases were present in 11 (55.0%), 9 (45.0%), and 13 (65.0%), respectively. The patient-based sensitivity/specificity/accuracy/area under the receiver-operating-characteristic curve (AUC) values for 11C-choline-PET/CT for diagnosing local lesions were 90.9% /100%/ 95.0% / 1.0, whereas those for FDG-PET/CT were 45.5% /100%/ 75.0% / 0.773. Those for 11C-choline-PET/CT for node metastasis were 88.9% /100%/ 95.0% / 0.944, and those for FDG-PET/CT were 44.4%/100%/75.0%/0.722. Those for 11C-choline-PET/CT for bone metastasis were 84.6%/100%/90.0%/0.951, and those for FDG-PET/CT were 76.9% /100%/ 85.0% / 0.962. The AUCs for local lesion and node metastasis differed significantly (p=0.0039, p=0.011, respectively). The lesion-based detection rates of 11C-choline compared to FDG PET/CT for local lesion, and node and bone metastases were 91.7% vs. 41.7%, 92.0% vs. 32.0%, and 94.8% vs. 83.0% (p=0.041, p=0.0030, p<0.0001), respectively. 11C-choline-PET/CT is more useful for the staging and restaging of prostate cancer than FDG-PET/CT in Japanese men.

Diagnostic performance of 11C-choline PET/CT and bone scintigraphy in the detection of bone metastases in patients with prostate cancer.

The aim of this study was to compare 11C-choline PET/CT and bone scintigraphy (BS) for detection of bone metastases in patients with prostate cancer. Twenty-one patients with histologically proven prostate cancer underwent 11C-choline PET/CT and BS before (n = 4) or after (n = 17) treatment. Patient-, region-, and lesion-based diagnostic performances of bone metastasis of both 11C-choline PET/CT and BS were evaluated using a five-point scale by two experienced readers. Bone metastases were present in 11 (52.4%) of 21 patients and 48 (32.7%) of 147 regions; 111 lesions were found to have bone metastases. Region-based analysis showed that the sensitivity, specificity, accuracy, and area under the receiver-operating-characteristic curves (AUC) of 11C-choline PET/CT were 97.9%, 99.0%, 98.6%, and 0.9989, respectively; those of BS were 72.9%, 99.0%, 90.5%, and 0.8386, respectively. Sensitivity, accuracy, and AUC significantly differed between the two methods (McNemar test, p = 0.0015, p = 0.0015, and p < 0.0001, respectively). 11C-choline PET/CT detected 110/111 metastatic lesions (99.1%); BS detected 85 (76.6%) (p < 0.0001). According to the CT morphological type, the visualization rates of 11C-choline-PET/BS were 100%/90.3% for the blastic type, 91.7%/8.3% for the lytic type, 100%/100% for the mixed type, and 100%/53.3% for the invisible type, respectively. Significant differences in blastic, lytic, and invisible types were observed between the two methods (p = 0.013, p = 0.0044, and p = 0.023, respectively). In conclusion, 11C-choline PET/CT had greater sensitivity and accuracy than BS for detection of bone involvement in patients with prostate cancer.

11C-Choline positive but 18F-FDG negative pancreatic metastasis from renal cell carcinoma on PET.

Choline is a new PET tracer, which uptake may occur via a choline-specific transporter protein and be accelerated during the proliferation of tumor cells. We report a 61-year-old woman with a metastatic pancreatic tumor from renal cell carcinoma, measuring 35×40 mm. PET scans demonstrated accumulation of 11C-choline in the metastatic pancreatic tumor, but no accumulation of 18F-FDG. Choline PET/CT may play a useful and complementary imaging modality, especially when FDG-PET/CT does not show expected findings or when the evaluation of tumor viability is needed, in patients with renal cell carcinoma.

Tumor response to neoadjuvant chemotherapy in patients with esophageal cancer assessed with CT and FDG-PET/CT - RECIST 1.1 vs. PERCIST 1.0.

PURPOSE: We compared the response classification systems Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0 for assessment of response to neoadjuvant chemotherapy in patients with esophageal cancer. MATERIALS AND METHODS: Prior to planned surgical resection, 62 patients with esophageal cancer underwent fluorodeoxyglucose (FDG)-PET/CT and contrast-enhanced CT examinations before and after receiving neoadjuvant chemotherapy. Primary tumor largest diameter, maximum standardized uptake value (SUVmax), peak lean body mass SUV (SULpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were determined. Patients were divided into responders (grade 1b-3) and non-responders (grade 0-1a) according to pathological response. RESULTS: Concordance between RECIST 1.1 and PERCIST 1.0 for response classification was seen in 28 (45.2%) patients. For 18 defined as responders, the number of metabolic responders (partial metabolic response + complete metabolic response) shown by PERCIST 1.0 was 17 and the number of anatomic responders (partial response + complete response) shown by RECIST 1.1 was 13. To distinguish responders from non-responders, the area under the receiver operating characteristics curve values for reduced primary tumor largest diameter, SUVmax, SULpeak, MTV, and TLG were 0.724, 0.775, 0.781, 0.756, and 0.759, respectively. An optimal percent decrease in largest diameter cut-off value of 39.2% was found to have 66.7% sensitivity and 70.5% specificity, while that for SULpeak of 55.8% was 77.8% and 75.0%, respectively. CONCLUSIONS: As compared to RECIST 1.1, PERSIST 1.0 may be more suitable for evaluation of neoadjuvant therapeutic response to esophageal cancer.

Prognostic value of FDG-PET and DWI in breast cancer.

OBJECTIVE: To investigate the prognostic value of preoperative FDG-PET/CT and diffusion weighted imaging (DWI) in patients with breast cancer. METHODS: A total of 73 patients with newly diagnosed invasive breast cancer who had undergone preoperative whole-body FDG-PET/CT and 3-Tesla breast MRI including DWI followed by surgery were identified. Effects of primary tumor PET parameters [maximum standardized uptake value (SUVmax), mean SUV (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] and DWI parameters [mean apparent diffusion coefficient (ADCmean) and minimum ADC (ADCmin)] including clinicopathologic factors on disease-free survival (DFS) were retrospectively evaluated using the log-rank and Cox methods. RESULTS: After a median overall follow-up of 32.3 months in all patients, 6 (8.2%) of the 73 patients had recurrence. Receiver operating characteristic curve analysis and log-rank tests showed that patients with a high primary tumor SUVmax (≥ 3.60), MTV (≥ 3.15), and TLG (≥ 16.0) had a significantly lower DFS rate than those with a low SUVmax (< 3.60), MTV (< 3.15), and TLG (< 16.0), respectively (p = 0.0054, p = 0.0054, and p < 0.0001, respectively). SUVmean, ADCmean, and ADCmin were not significantly associated with recurrence. Univariate analysis showed that SUVmax (p = 0.0054), MTV (p = 0.0054), TLG (p < 0.0001), tumor size (p = 0.0083), estrogen receptor negativity (p = 0.046), progesterone receptor negativity (p = 0.0023), human epidermal growth factor receptor 2 positivity (p = 0.043), and the presence of axillary lymph node metastasis (p = 0.0037) were also significantly associated with recurrence. However, in multivariate analysis, none of them were an independent factor. CONCLUSIONS: The preoperative SUVmax, MTV, and TLG of primary breast cancer are prognostic factors for recurrence, whereas ADC values are not.

Tiny Obturator Node Metastasis from Prostate Cancer Not Shown by FDG-PET/CT, CT, or MRI Detected by 11C-Choline PET/CT.

We report a 65-year-old male with histopathologically proven prostate cancer and multiple pelvic node metastases using a robotic-assisted radical prostatectomy procedure plus extended pelvic lymph node dissection. Positron emission tomography (PET) scan findings demonstrated a moderate accumulation of 11C-choline in a metastatic left obturator node sized 8 × 8 mm, though only a faint uptake of fluorodeoxyglucose (FDG) was noted. 11C-choline PET/computed tomography (CT) may be useful for the diagnosis of a tiny metastatic lymph node not demonstrated by CT, magnetic resonance imaging, or FDG-PET/CT and to determine the need for an extended pelvic lymph node dissection.

Pravastatin reduces radiation-induced damage in normal tissues.

Pravastatin is an inhibitor of 3-hydroxy-3-methyl- glutaryl-coenzyme A reductase that has been reported to have therapeutic applications in a range of inflammatory conditions. The aim of the present study was to assess the radioprotective effects of pravastatin in an experimental animal model. Mice were divided into two groups: The control group received ionizing radiation with no prior medication, while the pravastatin group received pravastatin prior to ionizing radiation. Pravastatin was administered orally at 30 mg/kg body weight in drinking water at 24 and 4 h before irradiation. Intestinal crypt epithelial cell survival and the incidence of apoptosis in the intestine and lung were measured post-irradiation. The effect of pravastatin on intestinal DNA damage was determined by immunohistochemistry. Finally, the effect of pravastatin on tumor response to radiotherapy was examined in a mouse mesothelioma xenograft model. Pravastatin increased the number of viable intestinal crypts and this effect was statistically significant in the ileum (P<0.0001). The pravastatin group showed significantly lower apoptotic indices in all examined parts of the intestine (P<0.0001) and tended to show reduced apoptosis in the lung. Pravastatin reduced the intestinal expression of ataxia-telangiectasia mutated and gamma-H2AX after irradiation. No apparent pravastatin-related differences were observed in the response of xenograft tumors to irradiation. In conclusion, pravastatin had radioprotective effects on the intestine and lung and reduced radiation-induced DNA double-strand breaks. Pravastatin may increase the therapeutic index of radiotherapy.

Polaprezinc protects normal intestinal epithelium against exposure to ionizing radiation in mice.

Polaprezinc (PZ), an antiulcer drug, has been reported to have antioxidant effects. The purpose of the present study was to assess the radioprotective effects of PZ in the normal intestine of C57BL/6J mice. PZ was orally administered at 100 mg/kg body weight in the drinking water. Firstly, the present study compared the survival of normal intestinal crypt epithelial cells with mice that received PZ prior to or following irradiation. Next, the present study examined the sequential changes of the incidence of apoptosis in the normal intestine of mice that received irradiation. The mice that received PZ prior to irradiation demonstrated a stronger protective effect on the normal intestine compared with those that received PZ after irradiation. The present study therefore administrated PZ 2 h before irradiation in the subsequent experiments. The mice receiving PZ developed fewer apoptotic cells in the duodenum, jejunum and ileum. Radiation-induced cell death occurred with a peak at position 10 or lower from the base of the crypt axis, and was subsequently reduced by PZ treatment. Pretreatment with PZ protected the normal intestinal tissues from radiation-induced apoptosis.

Arterial chemoradiotherapy for carcinomas of the external auditory canal and middle ear.

OBJECTIVES/HYPOTHESIS: The purpose of this study was to estimate the efficacy of superselective arterial chemoradiotherapy for locally advanced carcinomas of the external auditory canal and middle ear. STUDY DESIGN: A retrospective study of clinical data for consecutive patients with locally advanced carcinomas of the external auditory canal and middle ear. METHODS: Thirteen patients with locally advanced carcinomas of the external auditory canal and middle ear (T3: one patient, T4: 12 patients) were reviewed. The median follow-up duration in the living patients was 33 months. The total dose of radiation therapy was 60 Gy using conventional fractionation. Four, five, or six courses of a superselective arterial infusion (cisplatin 50 mg) were given weekly. RESULTS: The overall survival and progression-free survival rates at 2 years, calculated by the Kaplan-Meier method, were 58.7% and 53.8%, respectively. No late-phase adverse effects due to chemoradiation and no adverse effects due to catheterization were observed. CONCLUSIONS: These results suggest that superselective arterial chemoradiation can be a treatment option for locally advanced carcinomas of the external auditory canal and middle ear.

The threshold of hypothyroidism after radiation therapy for head and neck cancer: a retrospective analysis of 116 cases.

The purpose of the present study was to determine the risk factors for developing thyroid disorders based on a dose-volume histograms (DVHs) analysis. Data from a total of 116 consecutive patients undergoing 3D conformal radiation therapy for head and neck cancers was retrospectively evaluated. Radiation therapy was performed between April 2007 and December 2010. There were 108 males and 8 females included in the study. The median follow-up term was 24 months (range, 1-62 months). The thyroid function was evaluated by measuring thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels. The mean thyroid dose, and the volume of thyroid gland spared from doses ≥10, 20, 30 and 40 Gy (VS10, VS20, VS30 and VS40) were calculated for all patients. The thyroid dose and volume were calculated by the radiotherapy planning system (RTPS). The cumulative incidences of hypothyroidism were 21.1% and 36.4% at one year and two years, respectively, after the end of radiation therapy. In the DVH analyses, the patients who received a mean thyroid dose <30 Gy had a significantly lower incidence of hypothyroidism. The univariate analyses showed that the VS10, VS20, VS30 and VS40 were associated with the risk of hypothyroidism. Hypothyroidism was a relatively common type of late radiation-induced toxicity. A mean thyroid dose of 30 Gy may be a useful threshold for predicting the development of hypothyroidism after radiation therapy for head and neck cancers.

Polaprezinc reduces the severity of radiation-induced mucositis in head and neck cancer patients.

Polaprezinc (PZ), an antiulcer drug, has been reported to have antioxidant properties. The aim of the present study was to assess the feasibility and efficacy of administering PZ for radiation-induced mucositis in head and neck cancer patients. Patients with newly diagnosed head and neck cancer were enrolled in this prospective study. PZ was prepared as an oral rinse. The PZ oral rinse was used four times per day during the course of radiotherapy. Sequential changes in radiation mucositis were assessed during and after radiotherapy according to the Common Terminology Criteria for Adverse Events, version 3.0. Furthermore, a retrospective comparison analysis was performed to assess the efficacy of PZ for radiation-induced mucositis. A total of 32 patients were enrolled in the prospective study of the PZ oral rinse. Radiotherapy was performed up to a total dose of 60-66 Gy using a conventional schedule combined with chemotherapy. Of the 32 patients, 30 (93.8%) reported no complaints due to the PZ oral rinse. In addition, PZ was not associated with severe adverse effects. Among the patients who received PZ, grade 3 mucositis was observed in 29.0% based on the mucosal findings and in 39.3% based on the symptoms. In the patients who did not receive PZ, the incidence of grade 3 mucositis was 40.0% based on the mucosal findings and 60.7% based on the symptoms. Moreover, PZ promoted the recovery from mucositis caused by chemoradiotherapy and was not associated with reduced tumor response to radiotherapy. Therefore, the PZ oral rinse was well tolerated and proved to be efficient for the treatment of radiotherapy-induced oral mucositis.

Body mass index can affect gastrointestinal and genitourinary toxicity in patients with prostate cancer treated with external beam radiation therapy.

The aim of the present study was to determine the impact of obesity on radiation-induced gastrointestinal (GI) and genitourinary (GU) toxicity. The cases of 54 patients with prostate cancer, treated with three-dimensional conformal radiation therapy (RT), were reviewed. For each patient, the body mass index (BMI), distance between the prostate and rectum (D) on a computerised tomography scan and the dosimetric parameters of the rectum and bladder in the planning data of RT, were analyzed. GI and GU toxicity was assessed during and following RT. The results of the patients with a BMI of <25 (lower BMI) were compared with those of the patients with a BMI of ≥25 (higher BMI). The higher BMI group exhibited significantly lower doses of V60 and V65 in the rectum than the lower BMI group. No significant differences were found in D and bladder doses between the two groups. The incidence of acute GI and GU toxicity and late GI and GU toxicity were 41.7, 19.4, 35.3 and 5.7% in the lower BMI group, respectively, and 27.8, 27.8, 5.9 and 35.3% in the higher BMI group, respectively. In addition, a significant difference was found in the incidence of late GU toxicity between the two groups. Among patients who underwent RT for prostate cancer, those with higher BMIs had a tendency to show lower incidences of GI toxicity and higher incidences of GU toxicity than patients with lower BMIs. To conclude, an increased effort must be made to reduce rectal doses in patients with lower BMIs. Conversely, increased care for GU toxicity must be provided for overweight patients.

Neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer.

The purpose of this study was to examine the safety and feasibility of a novel protocol of neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer. A total of 56 patients with lower rectal cancer of cT3N1M0 (Stage III b) was treated with SC-HART followed by radical surgery, and were analyzed in the present study. SC-HART was performed with a dose of 2.5 Gy twice daily, with an interval of at least 6 hours between fractions, up to a total dose of 25 Gy (25 Gy in 10 fractions for 5 days) combined with S-1 for 10 days. Radical surgery was performed within three weeks following the end of the SC-HART. The median age was 64.6 (range, 39-85) years. The median follow-up term was 16.3 (range, 2-53) months. Of the 56 patients, 53 (94.4%) had no apparent adverse events before surgery; 55 (98.2%) completed the full course of neoadjuvant therapy, while one patient stopped chemotherapy because of Grade 3 gastrointestinal toxicity (CTCAE v.3). The sphincter preservation rate was 94.6%. Downstaging was observed in 45 patients (80.4%). Adjuvant chemotherapy was administered to 43 patients (76.8%). The local control rate, disease-free survival rate and disease-specific survival rate were 100%, 91.1% and 100%, respectively. To conclude, SC-HART combined with S-1 for locally advanced rectal cancer was well tolerated and produced good short-term outcomes. SC-HART therefore appeared to have a good feasibility for use in further clinical trials.