A predictive model to guide management of the overlap region between target volume and organs at risk in prostate cancer volumetric modulated arc therapy

Mattes, Malcolm D.,Lee, Jennifer C.,Elnaiem, Sara,Guirguis, Adel,Ikoro, N.C.,Ashamalla, Hani The Korean Society for Radiation Oncology 2014 Radiation Oncology Journal Vol.32 No.1

Purpose: The goal of this study is to determine whether the magnitude of overlap between planning target volume (PTV) and rectum ($Rectum_{overlap}$) or PTV and bladder ($Bladder_{overlap}$) in prostate cancer volumetric-modulated arc therapy (VMAT) is predictive of the dose-volume relationships achieved after optimization, and to identify predictive equations and cutoff values using these overlap volumes beyond which the Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) dose-volume constraints are unlikely to be met. Materials and Methods: Fifty-seven patients with prostate cancer underwent VMAT planning using identical optimization conditions and normalization. The PTV (for the 50.4 Gy primary plan and 30.6 Gy boost plan) included 5 to 10 mm margins around the prostate and seminal vesicles. Pearson correlations, linear regression analyses, and receiver operating characteristic (ROC) curves were used to correlate the percentage overlap with dose-volume parameters. Results: The percentage $Rectum_{overlap}$ and $Bladder_{overlap}$ correlated with sparing of that organ but minimally impacted other dose-volume parameters, predicted the primary plan rectum $V_{45}$ and bladder $V_{50}$ with $R^2$ = 0.78 and $R^2$ = 0.83, respectively, and predicted the boost plan rectum $V_{30}$ and bladder $V_{30}$ with $R^2$ = 0.53 and $R^2$ = 0.81, respectively. The optimal cutoff value of boost $Rectum_{overlap}$ to predict rectum $V_{75}$ >15% was 3.5% (sensitivity 100%, specificity 94%, p < 0.01), and the optimal cutoff value of boost $Bladder_{overlap}$ to predict bladder $V_{80}$ >10% was 5.0% (sensitivity 83%, specificity 100%, p < 0.01). Conclusion: The degree of overlap between PTV and bladder or rectum can be used to accurately guide physicians on the use of interventions to limit the extent of the overlap region prior to optimization.

Delayed radiation-induced inflammation accompanying a marked carbohydrate antigen 19-9 elevation in a patient with resected pancreatic cancer

Mattes, Malcolm D.,Cardinal, Jon S.,Jacobson, Geraldine M. The Korean Society for Radiation Oncology 2016 Radiation Oncology Journal Vol.34 No.2

Although carbohydrate antigen (CA) 19-9 is a useful tumor marker for pancreatic cancer, it can also become elevated from a variety of benign and malignant conditions. Herein we describe an unusual presentation of elevated CA 19-9 in an asymptomatic patient who had previously undergone adjuvant chemotherapy and radiation therapy for resected early stage pancreatic cancer. The rise in CA 19-9 might be due to delayed radiation-induced inflammation related to previous intra-abdominal radiation therapy with or without radiation recall induced by gemcitabine. After treatment with corticosteroids the CA 19-9 level decreased to normal, and the patient has not developed any evidence of recurrent cancer to date.

Dosimetric comparison of axilla and groin radiotherapy techniques for high-risk and locally advanced skin cancer

Mattes, Malcolm D.,Zhou, Ying,Berry, Sean L.,Barker, Christopher A. The Korean Society for Radiation Oncology 2016 Radiation Oncology Journal Vol.34 No.2

Purpose: Radiation therapy targeting axilla and groin lymph nodes improves regional disease control in locally advanced and high-risk skin cancers. However, trials generally used conventional two-dimensional radiotherapy (2D-RT), contributing towards relatively high rates of side effects from treatment. The goal of this study is to determine if three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or volumetric-modulated arc therapy (VMAT) may improve radiation delivery to the target while avoiding organs at risk in the clinical context of skin cancer regional nodal irradiation. Materials and Methods: Twenty patients with locally advanced/high-risk skin cancers underwent computed tomography simulation. The relevant axilla or groin planning target volumes and organs at risk were delineated using standard definitions. Paired t-tests were used to compare the mean values of several dose-volumetric parameters for each of the 4 techniques. Results: In the axilla, the largest improvement for 3D-CRT compared to 2D-RT was for homogeneity index (13.9 vs. 54.3), at the expense of higher lung $V_{20}$ (28.0% vs. 12.6%). In the groin, the largest improvements for 3D-CRT compared to 2D-RT were for anorectum $D_{max}$ (13.6 vs. 38.9 Gy), bowel $D_{200cc}$ (7.3 vs. 23.1 Gy), femur $D_{50}$ (34.6 vs. 57.2 Gy), and genitalia $D_{max}$ (37.6 vs. 51.1 Gy). IMRT had further improvements compared to 3D-CRT for humerus $D_{mean}$ (16.9 vs. 22.4 Gy), brachial plexus $D_5$ (57.4 vs. 61.3 Gy), bladder $D_5$ (26.8 vs. 36.5 Gy), and femur $D_{50}$ (18.7 vs. 34.6 Gy). Fewer differences were observed between IMRT and VMAT. Conclusion: Compared to 2D-RT and 3D-CRT, IMRT and VMAT had dosimetric advantages in the treatment of nodal regions of skin cancer patients.

The protective and antioxidant effect of Solanum lycopersicum extract in liver fibrosis induced rats

Andrea mattes,Kim KiYoung,Kim HeeSeok,Lee SangHee,Park JunHo,Oh Semi 大韓藥學會 2003 大韓藥學會 總會 및 學術大會 Vol.2003 No.1

Delayed radiation-induced inflammation accompanying a marked carbohydrate antigen 19-9 elevation in a patient with resected pancreatic cancer

Malcolm D. Mattes,Jon S. Cardinal,Geraldine M. Jacobson 대한방사선종양학회 2016 Radiation Oncology Journal Vol.34 No.2

Although carbohydrate antigen (CA) 19-9 is a useful tumor marker for pancreatic cancer, it can also become elevated from a variety of benign and malignant conditions. Herein we describe an unusual presentation of elevated CA 19-9 in an asymptomatic patient who had previously undergone adjuvant chemotherapy and radiation therapy for resected early stage pancreatic cancer. The rise in CA 19-9 might be due to delayed radiation-induced inflammation related to previous intra-abdominal radiation therapy with or without radiation recall induced by gemcitabine. After treatment with corticosteroids the CA 19-9 level decreased to normal, and the patient has not developed any evidence of recurrent cancer to date.

The incidence of pelvic and para-aortic lymph node metastasis in uterine papillary serous and clear cell carcinoma according to the SEER registry

Malcolm D. Mattes, MD,Jennifer C. Lee,Daniel J. Metzger,Hani Ashamalla,Evangelia Katsoulakis 대한부인종양학회 2015 Journal of Gynecologic Oncology Vol.26 No.1

Objective: In this study we utilized the Surveillance, Epidemiology and End-Results (SEER) registry to identify risk factors for lymphatic spread and determine the incidence of pelvic and para-aortic lymph node metastases in patients with uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC) who underwent complete surgical staging and lymph node dissection. Methods: Nine hundred seventy-two eligible patients diagnosed between 1998 to 2009 with International Federation of Gynecology and Obstetrics (FIGO) 1988 stage IA-IVA UPSC (n=685) or UCCC (n=287) were identified for analysis. Binomial logistic regression was used to determine risk factors for lymph node metastasis, with the incidence of pelvic and para-aortic lymph node metastases reported for each FIGO primary tumor stage. The Cox proportional hazards regression model was used to determine factors associated with overall survival. Results: FIGO primary tumor stage was the only independent risk factor for lymph node metastasis (p<0.01). The incidence of pelvis-only and para-aortic lymph node involvement according to the FIGO primary tumor stage were as follows: IA (2.3%/3.8%), IB (7.5%/5.2%), IC (22.5%/16.9%), IIA (20.8%/13.2%), IIB (25.7%/14.9%), and III/IV (25.7%/24.3%). Prognostic factors for overall survival included lymph node involvement (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.09 to 1.85; p<0.01), patient age >60 years (HR, 1.70; 95% CI, 1.21 to 2.41; p<0.01), and advanced FIGO primary tumor stage (p<0.01). Tumor grade, histologic subtype, and patient race did not predict for either lymph node metastasis or overall survival. Conclusion: There is a high incidence of both pelvic and para-aortic lymph node metastases for FIGO stages IC and above uterine papillary serous and clear cell carcinomas, suggesting a potential role for lymph node-directed therapy for these patients.

Breast Cancer Subtype as a Predictor of Lymph Node Metastasis according to the SEER Registry

Malcolm D. Mattes,Jay K. Bhatia,Daniel Metzger,Hani Ashamalla,Evangelia Katsoulakis 한국유방암학회 2015 Journal of breast cancer Vol.18 No.2

Purpose: Breast cancer subtype correlates with response to systemic therapy and overall survival (OS), but its impact on lymphatic spread is incompletely understood. In this study, we used the Surveillance, Epidemiology, and End Results registry to assess whether the subtype can predict the presence of nodal metastasis or advanced nodal stage in breast cancer. Methods: A total of 7,274 eligible patients diagnosed with T1-3 infiltrating ductal carcinoma with known estrogen or progesterone hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status, who underwent surgical excision of the primary tumor and pathologic lymph node evaluation, were included in this analysis. Patients were categorized into four breast cancer subtypes: HR+/HER2−; HR+/HER2+; HR−/HER2+; and HR−/HER2−. Binary logistic regression analysis was used to determine whether breast cancer subtype, tumor size, tumor grade, patient race, and patient age at diagnosis are independently predictive of lymph node positivity or advanced nodal stage. The Pearson chi-square test was used to determine whether progesterone receptor (PR) status had an impact on the incidence of lymph node positivity in estrogen receptor (ER) positive patients. Results: Independent predictors of nodal positivity included breast cancer subtype (p=0.040), tumor size (p<0.001), tumor grade (p<0.001), and patient age (p<0.001), whereas only tumor size (p<0.001), grade (p=0.001), and patient age (p=0.005) predicted advanced nodal stage. Triple-negative cancers had a significantly lower risk of nodal positivity than the HR+/HER2− subtype (odds ratio, 0.686; p=0.004), but no other significant differences between subtypes were observed. There was also no difference in lymph node positivity between PR+ and PR− tumors amongst ER+/HER2− (p=0.228) or ER+/HER2+ tumors (p=0.713). Conclusion: The HR+/HER2− breast cancer subtype has a higher rate of lymph node involvement at diagnosis than the triple-negative subtype. These findings may play a role in guiding regional management considerations if confirmed in further studies.

Dosimetric comparison of axilla and groin radiotherapy techniques for high-risk and locally advanced skin cance

Malcolm D. Mattes,Ying Zhou,Sean L. Berry,Christopher A. Barker 대한방사선종양학회 2016 Radiation Oncology Journal Vol.34 No.2

Purpose: Radiation therapy targeting axilla and groin lymph nodes improves regional disease control in locally advanced and high-risk skin cancers. However, trials generally used conventional two-dimensional radiotherapy (2D-RT), contributing towards elatively high rates of side effects from treatment. The goal of this study is to determine if three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or volumetric-modulated arc therapy (VMAT) may improve radiation delivery to the target while avoiding organs at risk in the clinical context of skin cancer regional nodal irradiation. Materials and Methods: Twenty patients with locally advanced/high-risk skin cancers underwent computed tomography simulation. The relevant axilla or groin planning target volumes and organs at risk were delineated using standard definitions. Paired t-tests were used to compare the mean values of several dose-volumetric parameters for each of the 4 techniques. Results: In the axilla, the largest improvement for 3D-CRT compared to 2D-RT was for homogeneity index (13.9 vs. 54.3), at the expense of higher lung V20 (28.0% vs. 12.6%). In the groin, the largest improvements for 3D-CRT compared to 2D-RT were for anorectum Dmax (13.6 vs. 38.9 Gy), bowel D200cc (7.3 vs. 23.1 Gy), femur D50 (34.6 vs. 57.2 Gy), and genitalia Dmax (37.6 vs. 51.1 Gy). IMRT had further improvements compared to 3D-CRT for humerus Dmean (16.9 vs. 22.4 Gy), brachial plexus D5 (57.4 vs. 61.3 Gy), bladder D5 (26.8 vs. 36.5 Gy), and femur D50 (18.7 vs. 34.6 Gy). Fewer differences were observed between IMRT and VMAT. Conclusion: Compared to 2D-RT and 3D-CRT, IMRT and VMAT had dosimetric advantages in the treatment of nodal regions of skin cancer patients.

A predictive model to guide management of the overlap region between target volume and organs at risk in prostate cancer volumetric modulated arc therapy

Malcolm D,Mattes,Jennifer C,Lee,Sara Elnaiem,Adel Guirguis,N,C,Ikoro,Hani Ashamalla 대한방사선종양학회 2014 Radiation Oncology Journal Vol.32 No.1

Purpose: The goal of this study is to determine whether the magnitude of overlap between planning target volume (PTV) and rectum (Rectumoverlap) or PTV and bladder (Bladderoverlap) in prostate cancer volumetric-modulated arc therapy (VMAT) is predictive of the dose-volume relationships achieved after optimization, and to identify predictive equations and cutoff values using these overlap volumes beyond which the Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) dose-volume constraints are unlikely to be met. Materials and Methods: Fifty-seven patients with prostate cancer underwent VMAT planning using identical optimization conditions and normalization. The PTV (for the 50.4 Gy primary plan and 30.6 Gy boost plan) included 5 to 10 mm margins around the prostate and seminal vesicles. Pearson correlations, linear regression analyses, and receiver operating characteristic (ROC) curves were used to correlate the percentage overlap with dose-volume parameters. Results: The percentage Rectumoverlap and Bladderoverlap correlated with sparing of that organ but minimally impacted other dose-volume parameters, predicted the primary plan rectum V45 and bladder V50 with R2 = 0.78 and R2 = 0.83, respectively, and predicted the boost plan rectum V30 and bladder V30 with R2 = 0.53 and R2 = 0.81, respectively. The optimal cutoff value of boost Rectumoverlap to predict rectum V75 >15% was 3.5% (sensitivity 100%, specificity 94%, p < 0.01), and the optimal cutoff value of boost Bladderoverlap to predict bladder V80 >10% was 5.0% (sensitivity 83%, specificity 100%, p < 0.01). Conclusion: The degree of overlap between PTV and bladder or rectum can be used to accurately guide physicians on the use of interventions to limit the extent of the overlap region prior to optimization.

Two-photon fluorescence lifetime imaging of intracellular chloride in cockroach salivary glands

Hille, Carsten,Lahn, Mattes,Lohmannsroben, Hans-Gerd,Dosche, Carsten Korean Society of Photoscience 2009 Photochemical & photobiological sciences Vol.8 No.3

Although chloride plays an important role in many cellular processes, there is a lack of data about intracellular chloride concentrations $[Cl^-]_i$, particularly due to technical problems. To overcome that, in this study fluorescence lifetime imaging microscopy in the time-domain by using time-correlated single-photon counting was combined with two-photon excitation (2P-FLIM). This 2P-FLIM setup has been successfully used with the $Cl^-$-sensitive fluorescent dye N-(ethoxycarbonylmethyl)-6-methoxy-quinolinium bromide (MQAE) in order to measure $[Cl^-]_i$ in cockroach salivary glands, a well-established model system for studying epithelial ion transport processes. MQAE was well suitable for two-photon excitation, when loaded into cells, and displayed a sufficient dynamic range of its fluorescence decay time changes in response to variation of $[Cl^-]_i$ according to the Stern-Volmer relationship. On this basis a uniform $[Cl^-]_i$ in the range of 42.80 mM with a mean value of $59\;mM{\pm}1\;mM$ was found in resting cockroach salivary ducts, indicating active $Cl^-$ accumulation. However, exposure to $Cl^-$-free saline caused only a moderate $[Cl^-]_i$ drop to $48\;mM{\pm}4\;mM$, suggesting a relatively low basolateral $Cl^-$ permeability in ducts, at least under resting conditions. Additionally, bath application of the biogenic amine dopamine, known to stimulate the saliva modification in the ducts, caused no significant $[Cl^-]_i$ changes. These results suggest a more complex scenario of $[Cl^-]_i$ homeostasis in cockroach salivary ducts. In conclusion, 2P-FLIM seems to be a suitable technique for quantitative $[Cl^-]_i$ measurements in many biological systems.