A retrospective study on the potential of 99m Tc-HDP imaging before therapy for individualizing treatments with 223 Ra-Cl2 for metastatic castration resistant prostate cancer.

PURPOSE: Research on dose-effect correlation is necessary to move toward an individualization of treatments of metastatic castration resistant prostate cancer (mCRPC) with 223 Ra-Cl2 . We first looked for a possible correlation of 99m Tc-HDP lesion uptake in pretreatment whole-body scans (WBSs) with lesion absorbed dose. Moreover, we looked for a possible correlation of 99m Tc-HDP lesion uptake in pretreatment WBSs and of lesion absorbed dose with relative change in the 99m Tc-HDP lesion uptake obtained from pre- and post-treatment WBSs in patients treated for mCRPC with six cycles of 223 Ra-Cl2 . METHODS: Eleven patients received six cycles of 55 kBq/kg of 223 Ra-Cl2 separated by 4 weeks. In addition, one patient received concomitant treatment with abiraterone and two patients with enzalutamide. The 99m Tc-HDP WBSs were acquired before the first cycle and after the sixth cycle of the treatment. For the lesions with the higher 99m Tc-HDP uptake, the absorbed dose was calculated for the first cycle. Lesion volume was determined from 99m Tc-HDP SPECT/CT images before the first cycle and 223 Ra-Cl2 activity in the lesions was determined from 223 Ra-Cl2 planar images after the first cycle. The effect of the treatment was evaluated from the relative change of the mean and the maximum counts in the lesions, both estimated from the WBSs acquired before the first cycle and after the sixth cycle. RESULTS: The absorbed dose was calculated for 30 lesions, with values ranging between 0.4 and 3.8 Gy (mean 1.5 Gy). A significant (P < 0.05) high positive linear correlation was found between the lesion absorbed dose in the first treatment cycle and the mean and maximum counts in the lesions in the WBSs acquired before the first cycle (R = 0.75 and 0.76, respectively). The relative change of the mean and the maximum counts in the lesions in the 99m Tc-HDP WBSs showed a significant (P < 0.05) high positive logarithmic correlation with the 99m Tc-HDP mean and maximum counts in the lesions before the first cycle (R = 0.79 and 0.78, respectively). Lastly, a significant (P < 0.05) high positive logarithmic correlation was also found between the relative change of the mean and the maximum counts in the lesions in the 99m Tc-HDP WBSs and the lesion absorbed dose (R = 0.86 and 0.85, respectively). For this correlation the influence of the administered activity and of the concomitant treatments was not found to be significant (P > 0.05). CONCLUSIONS: The high correlations found for the 99m Tc-HDP lesion uptake before the first cycle lesion with the relative change in the 99m Tc-HDP lesion uptake after the six cycles of 223 Ra-Cl2 , and with the lesion absorbed dose in the first cycle show the potential of pretreatment 99m Tc-HDP imaging in order to personalize the performance of these treatments.

Microdosimetry-based determination of tumour control probability curves for treatments with 225Ac-PSMA of metastatic castration resistant prostate cancer.

We performed Monte Carlo simulations in order to determine, by means of microdosimetry calculations, tumour control probability (TCP) curves for treatments with 225Ac-PSMA of metastatic castration resistant prostate cancer (mCRPC). Realistic values of cell radiosensitivity, nucleus size and lesion size were used for calculations. As the cell radiosensitivity decreased, the nucleus size decreased and the lesion size increased, the absorbed dose to reach a given TCP increased. The widest variations occurred with regard to the cell radiosensitivity. For the Monte Carlo simulations, in order to address a non-uniform PSMA expression, different 225Ac-PSMA distributions were considered. The effect of these different PSMA distributions resulted in small variations in the TCP curves (maximum variation of 5%). Absorbed doses to reach a TCP of 0.9 for a uniform 225Ac-PSMA distribution, considering a relative biological effectiveness (RBE) of 5, ranged between 35.0 Gy and 116.5 Gy. The lesion absorbed doses per administered activity reported in a study on treatments with 225Ac-PSMA of mCRPC ranged between 1.3 Gy MBq-1 and 9.8 Gy MBq-1 for a RBE = 5. For a 70 kg-patient to whom 100 kBq kg-1 of 225Ac-PSMA are administered, the range of lesion absorbed doses would be between 9.1 Gy and 68.6 Gy. Thus, for a single cycle of 100 kBq kg-1, a number of lesions would not receive an absorbed dose high enough to reach a TCP of 0.9.

A prospective analysis of factors that influence weight loss in patients undergoing radiotherapy.

Malnutrition occurs frequently in patients with cancer. Indeed, a variety of nutritional and tumor-related factors must be taken into account in these patients. Recognizing this relationship, we aimed to prospectively evaluate the risk factors that influence weight loss in patients undergoing radiotherapy with oral nutritional supplementation and dietetic counseling. Weight loss of 74 patients during radiotherapy and 1 month after treatment was analyzed. Parameters such as age, gender, tumor location, tumor stage, Eastern Cooperative Oncology Group performance status (ECOG PS) score, and the use of chemotherapy were analyzed to evaluate their influence on weight loss. All patients underwent oral nutritional supplementation and dietetic counseling. Forty-six (65.7%) patients lost weight, with a mean weight loss of (4.73 ± 3.91) kg, during radiotherapy. At 1 month after treatment, 45 (66.2%) patients lost weight, presenting a mean weight loss of (4.96 ± 4.04) kg, corresponding to a (6.84 ± 5.24)% net reduction from their baseline weight. Head and neck cancer patients had a mean weight loss of (3.25 ± 5.30) kg, whereas the remaining patients had a mean weight loss of (0.64 ± 2.39) kg (P = 0.028) during radiotherapy. In the multivariate analysis, the head and neck tumor location (P = 0.005), use of chemotherapy (P = 0.011), and ECOG PS score of 2-3 (P = 0.026) were considered independent risk factors. Nutritional status and parameters, such as tumor location (especially the head and neck), the use of chemotherapy, and the ECOG PS score, should be evaluated before radiotherapy because these factors can influence weight loss during radiotherapy and 1 month after treatment.

The role of re-irradiation of secondary and recurrent head and neck carcinomas. Is it a potentially curative treatment? A practical approach.

Despite aggressive efforts to cure head and neck cancer patients, including altered fractionation and the addition of chemotherapy to radiation, locoregional recurrence remains a serious issue to face in clinical practice. Indeed, recurrent and second primary tumors occurring in previously irradiated area are common clinical challenge. Whenever possible, patients are advised to undergo salvage surgery. Nevertheless, few patients are suitable candidates for curative resection. In such cases, chemotherapy alone has traditionally been considered, with a poor response rate. It has been questioned whether re-irradiation toxicity outweighs the potential benefits, considering that the median survival of re-irradiated patients marginally exceeds the benefits observed with chemotherapy alone. However, full-dose re-irradiation is a viable treatment option, offering long-term survival for selected patients. Moreover, several prognostic factors should be considered for patients undergoing re-irradiation, such as basic patient characteristics, performance status, the location and extension of recurrent disease, patient co-morbidities, current speech and swallowing function, the interval from the initial radiation therapy to recurrence, previously received doses by critical structures and prior treatment toxicity. Nevertheless, several questions remain unanswered. The purpose of this review is to evaluate the major issues in the field of re-irradiation regarding the current evidence. Therefore, the major selection criteria and new treatment strategies are discussed to define the ideal candidates to undergo re-irradiation and describe a practical approach to these patients. Given the limited evidence in this field, the optimal treatment of recurrent and second primary cancers remains to be defined. Future prospective study of this approach is warranted.