When does a melanoma metastasize? Implications for management.

Selecting which patients with clinically-localized melanoma require treatment other than wide excision of the primary tumor is based on the risk or presence of metastatic disease. This in turn is linked to survival. Knowing if and when a melanoma is likely to metastasize is therefore of great importance. Several studies employing a range of different methodologies have suggested that many melanomas metastasize long before the primary lesion is diagnosed. Therefore, waiting for dissemination of metastatic disease to become evident before making systemic therapy available to these patients may be less effective than giving them post-operative adjuvant therapy initially if the metastatic risk is high. The identification of these high-risk patients will assist in selecting those to whom adjuvant systemic therapy can most appropriately be offered. Further studies are required to better identify high-risk patients whose primary melanoma is likely to have already metastasized.

Tumor Doubling Time and Screening Interval.

The goal of screening is to detect breast cancers when still curable to decrease breast cancer-specific mortality. Breast cancer screening in the United States is routinely performed with digital mammography and digital breast tomosynthesis. This article reviews breast cancer doubling time by tumor subtype and examines the impact of doubling time on breast cancer screening intervals. By the article's end, the reader will be better equipped to have informed discussions with patients and medical professionals regarding the benefits and disadvantages of the currently recommended screening mammography intervals.

Primary Hepatic Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders After Methotrexate Therapy.

Prior reports described cases of lymphoproliferative diseases occurring after methotrexate (MTX) administration, which are called methotrexate-associated lymphoproliferative disorders (MTX-LPDs). It has become clear that these lymphoproliferative diseases also occur following treatment with other immunosuppressive drugs, and they have been termed as other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs). In most of these cases, the duration of immunosuppressive drugs is very long, on the order of years. In the present study, we evaluated the development of lymphoproliferative disease despite the short duration of immunosuppressive treatment and determined the tumor doubling time. A 71-year-old woman was diagnosed with adult-onset Still's disease. The patient was administered prednisone 30 mg per day starting on February 25, 2022 and MTX 6 mg per week starting 2 weeks later. Because she was a hepatitis B virus (HBV) carrier, nucleic acid analog therapy was also started to prevent HBV activation. Eight weeks later, biweekly tocilizumab was started. After 5 months of MTX administration, a solitary liver tumor measuring 37 × 32 mm2 was detected. Three months later, repeat computed tomography revealed that the liver tumor had grown rapidly to 7 cm in diameter. We considered the possibility of OIIA-LPDs and stopped MTX therapy. Biopsy specimens of the liver tumor exhibited lymphocyte proliferation, which was consistent with OIIA-LPDs. The doubling time for tumor growth was 33 days. Despite withdrawing MTX for 6 weeks, the tumor continued to grow, and thus, the patient was referred to the hematology unit. In previously reported cases of MTX-LPDs of hepatic origin, the average duration of MTX administration was 7.3 (2 - 13) years. This report describes a primary hepatic OIIA-LPDs-associated tumor that rapidly increased in size after an extremely short period of MTX administration.

Progesterone from ovulatory menstrual cycles is an important cause of breast cancer.

Many factors, including reproductive hormones, have been linked to a woman's risk of developing breast cancer (BC). We reviewed the literature regarding the relationship between ovulatory menstrual cycles (MCs) and BC risk. Physiological variations in the frequency of MCs and interference with MCs through genetic variations, pathological conditions and or pharmaceutical interventions revealed a strong link between BC risk and the lifetime number of MCs. A substantial reduction in BC risk is observed in situations without MCs. In genetic or transgender situations with normal female breasts and estrogens, but no progesterone (P4), the incidence of BC is very low, suggesting an essential role of P4. During the MC, P4 has a strong proliferative effect on normal breast epithelium, whereas estradiol (E2) has only a minimal effect. The origin of BC has been strongly linked to proliferation associated DNA replication errors, and the repeated stimulation of the breast epithelium by P4 with each MC is likely to impact the epithelial mutational burden. Long-lived cells, such as stem cells, present in the breast epithelium, can carry mutations forward for an extended period of time, and studies show that breast tumors tend to take decades to develop before detection. We therefore postulate that P4 is an important factor in a woman's lifetime risk of developing BC, and that breast tumors arising during hormonal contraception or after menopause, with or without menopausal hormone therapy, are the consequence of the outgrowth of pre-existing neoplastic lesions, eventually stimulated by estrogens and some progestins.

Tumor doubling time as preoperative predictor of malignancy and recurrence in newly diagnosed meningioma.

Most meningiomas are benign, and the indications for surgery are determined by size and symptoms, but some are malignant and have a high recurrence rate. Currently, no preoperative prognostic factors have been established. The purpose of this study was to investigate whether tumor doubling time (Td) is useful in predicting tumor prognosis. Patients who underwent surgery for newly diagnosed meningioma at our hospital between 2007 and 2021 with preoperative magnetic resonance (MR) imaging evaluation over a period of 6 months were included in this study. We calculated the Td from the preoperative MR images and examined the correlation between Td and WHO grade, MIB-1 SI, and other conditions. A total of 269 newly diagnosed meningiomas were operated on during the study period, of which 62 met inclusion criteria. The median Td was 1082 days (54-8579 days), and MIB-1 SI was 2.45% (0.7-14.6%). Td and MIB-1 SI had a negative correlation (r = - 0.319, p = 0.0122). MIB-1 SI was higher in patients with Td < 3 years than in those with Td ≥ 3 (p = 0.005), and the incidence of high WHO grade (grade2) was higher in patients with Td < 1 year than in patients with Td ≥ 1 (p = 0.014). Meningiomas with Td < 3 years had significantly higher MIB-1 SI, and tumors with Td < 1 year had a higher likelihood of malignancy. Therefore, early treatment should be considered in patients with short Td meningioma even if asymptomatic, and further consideration could be given to radical resection at the time of surgery.

Preoperative Prediction of Intracranial Meningioma Grade Using Conventional CT and MRI.

Objective Preoperative diagnosis of tumor grade can assist in treatment-related decision-making for patients with intracranial meningioma. This study aimed to distinguish between high-grade and low-grade meningiomas using conventional CT and MRI. Methodology We retrospectively analyzed 173 consecutive patients with intracranial meningioma (149 low-grade and 24 high-grade tumors) who were treated surgically at the National Hospital Organization Kyushu Medical Center from 2008 to 2020. Clinical and radiological features, including tumor doubling time (Td) and relative growth rate (RGR), were compared between low-grade and high-grade meningiomas. Results Multivariate logistic regression analysis showed that symptomatic tumor (p=0.001), non-skull base location (p=0.006), irregular tumor shape (p=0.043), tumor heterogeneity (p=0.025), and peritumoral brain edema (p=0.003) were independent predictors of high-grade meningioma. In 53 patients who underwent surgery because of tumor progression, progression to symptoms (p=0.027), intratumoral heterogeneity (p<0.001), peritumoral brain edema (p=0.001), larger tumor volume (p=0.005), shorter Td (p<0.001), and higher RGR (P<0.001) were significantly associated with high-grade meningioma. Receiver operating characteristics (ROC) curve analysis showed that the optimal Td and annual RGR cut-off values to distinguish high-grade from low-grade meningioma were 460.5 days and 73.2%, respectively (100% sensitivity and 78.6% specificity). Conclusion Based on our findings, conventional CT and MRI are useful methods to predict meningioma grades before surgery. High-grade lesions are associated with non-skull base location, irregular tumor shape, intratumoral heterogeneity, and peritumoral brain edema. High-grade meningioma should be suspected in tumors that exhibit Td <460.5 days or annual RGR >73.2% or those that develop intratumoral heterogeneity or surrounding brain edema on surveillance imaging.

Surgical indication of pulmonary metastasis arising from osteosarcoma or soft tissue sarcoma.

OBJECTIVES: Metastasectomy is often the local treatment for pulmonary metastases arising from osteosarcoma or soft tissue sarcoma. However, there have been few investigations on the outcomes of patients who undergo this procedure. In this study, we identified prognostic factors in patients with pulmonary metastases arising from osteosarcoma and soft tissue sarcoma to determine more appropriate eligibility criteria for metastasectomy. METHODS: We retrospectively examined 37 patients who underwent metastasectomy of pulmonary nodules arising from osteosarcomas or soft tissue sarcomas at our institute between 2005 and 2020. Overall and recurrence-free survival intervals were determined using univariate and multivariate analyses. RESULTS: A tumor doubling time > 1 month and a primary tumor histological type of osteosarcoma were independent predictors of longer overall survival on multivariate analysis (hazard ratios: 3.618 and 2.979, p = 0.00986 and 0.0373, respectively). Moreover, a > 1-month tumor doubling time and > 10-cm diameter of the primary tumor were independent predictors of longer recurrence-free survival (hazard ratios: 3.293 and 2.67, p = 0.0121 and 0.0134, respectively). Patients who underwent repeat pulmonary metastasectomy after complete resection of sarcoma-derived pulmonary metastases had significantly longer overall survival than those who did not (median: 5.91 years vs. 0.81 years, p < 0.0001). CONCLUSIONS: Tumor doubling time is a significant predictor of clinical outcomes in patients who undergo resection of pulmonary metastases originating from sarcomas. The surgical indication for this procedure should be decided carefully, particularly for patients with metastatic lesion doubling times ≤ 1 month.

A novel tumor doubling time-related immune gene signature for prognosis prediction in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) has become a global health issue of wide concern due to its high prevalence and poor therapeutic efficacy. Both tumor doubling time (TDT) and immune status are closely related to the prognosis of HCC patients. However, the association between TDT-related genes (TDTRGs) and immune-related genes (IRGs) and the value of their combination in predicting the prognosis of HCC patients remains unclear. The current study aimed to discover reliable biomarkers for anticipating the future prognosis of HCC patients based on the relationship between TDTRGs and IRGs. METHODS: Tumor doubling time-related genes (TDTRGs) were acquired from GSE54236 by using Pearson correlation test and immune-related genes (IRGs) were available from ImmPort. Prognostic TDTRGs and IRGs in TCGA-LIHC dataset were determined to create a prognostic model by the LASSO-Cox regression and stepwise Cox regression analysis. International Cancer Genome Consortium (ICGC) and another cohort of individual clinical samples acted as external validations. Additionally, significant impacts of the signature on HCC immune microenvironment and reaction to immune checkpoint inhibitors were observed. RESULTS: Among the 68 overlapping genes identified as TDTRG and IRG, a total of 29 genes had significant prognostic relevance and were further selected by performing a LASSO-Cox regression model based on the minimum value of λ. Subsequently, a prognostic three-gene signature including HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1), C-type lectin domain family 1 member B (CLEC1B), and Collectin sub-family member 12 (COLEC12) was finally identified by stepwise Cox proportional modeling. The signature exhibited superior accuracy in forecasting the survival outcomes of HCC patients in TCGA, ICGC and the independent clinical cohorts. Patients in high-risk subgroup had significantly increased levels of immune checkpoint molecules including PD-L1, CD276, CTLA4, CXCR4, IL1A, PD-L2, TGFB1, OX40 and CD137, and are therefore more sensitive to immune checkpoint inhibitors (ICIs) treatment. Finally, we first found that overexpression of CLEC1B inhibited the proliferation and migration ability of HuH7 cells. CONCLUSIONS: In summary, the prognostic signature based on TDTRGs and IRGs could effectively help clinicians classify HCC patients for prognosis prediction and individualized immunotherapies.

Relationship between the three-dimensionally measured tumor doubling time of lung cancer and underlying interstitial lung disease: A retrospective case-control study.

OBJECTIVE: The coexistence of interstitial lung disease (ILD) is associated with poor prognosis in patients with lung cancer. The tumor doubling time (TDT) of lung cancer reflects cancer aggressiveness and is related to its prognosis. However, the relationship between the TDT of lung cancer and underlying ILD has not been fully evaluated. This study aimed to identify this crucial relationship. MATERIALS AND METHODS: Patients with lung cancer who underwent surgery between 2007 and 2020 were reviewed retrospectively. The propensity score matching method was used to balance the characteristics of patients with ILD (n = 100) and those without ILD (n = 100). TDT was calculated based on the difference of three-dimensional volumes defined from the two-time CT scans before surgery. We compared the TDT of lung cancer and other characteristics between the two groups. RESULTS: The median TDT of all patients was 149 days. The TDT was significantly shorter in patients with ILD (134 days) than in those without (204 days). The rate of short-term tumor enlargement (TDT < 90 days) was significantly higher in patients with ILD than in those without ILD, and ILD was an independent factor related to short-term tumor enlargement (odds ratio, 2.30; p = 0.015). We focused on 25 patients with usual interstitial pneumonitis (UIP) findings of patients with ILD. However, the presence of the UIP pattern was not related to the TDT among patients with ILD. CONCLUSION: ILD was an independent predictor of short-term tumor enlargement in lung cancer patients, regardless of the presence of the UIP pattern.

Has tumor doubling time in breast cancer changed over the past 80 years? A systematic review.

Over the past century, epidemiologic changes and implementation of screening may have had an impact on tumor doubling time in breast cancer. Our study was designed to evaluate changes in tumor doubling time in breast cancer over the past 80 years. A systematic review of published literature and meta-regression analysis was performed. An online electronic database search was undertaken using the PubMed platform from inception until June 2020. All studies that measured tumor doubling time in breast cancer were included. A total of 151 publications were retrieved. Among them, 16 full-text articles were included in the qualitative analysis. An exponential growth model was used for quantitative characterization of tumor growth rate. Tumor doubling time has remained stable over the past 80 years. Recent studies have not only identified "fast growing tumor" (grade 3, human epidermal growth factor receptor 2-positive, triple-negative, or tumor with an elevated Ki-67) but also "inactive breast cancer" feeding the ongoing debate of overdiagnosis due to screening programs. The stability of tumor doubling time over the past 80 years, despite increasing and changing risk factors, supports the validity for our screening guidelines. Prospective studies based on more precise measurement of tumor size and adjustment for tumor characteristics are necessary to more clearly characterize the prognostic and predictive impact of tumor doubling time in breast cancer.

The Impact of 5-Year Tumor Doubling Time to Predict the Subsequent Long-Term Natural History of Asymptomatic Meningiomas.

OBJECTIVE: Meningiomas are the most frequent primary brain tumors. The long-term natural history of asymptomatic meningiomas remains unclear and difficult to predict accurately, however. The purpose of this study was to determine the subsequent course of asymptomatic meningiomas preceded by 5 years of no treatment. METHODS: We retrospectively studied patients with radiologically suspected intracranial asymptomatic meningiomas preceded by 5 years of no treatment. We volumetrically measured the lesions' chronological changes during the initial 5 years to obtain the 5-year tumor doubling time (5y-TdT). RESULTS: A total of 201 cases met the inclusion criteria. They were further divided into 3 subgroups: those who remained asymptomatic (group A; 174 cases), those who developed neurological symptoms and underwent treatment (group B; 8 cases), and those who received intentional intervention for a preventative reason (group C; 19 cases). 5y-TdT of group B (median: 46.5 months) was significantly shorter than that of group A (median: 216.3 months) (P < 0.001). Progression-free survival (PFS) was significantly different between tumors that exhibited 5y-TdT ≥ 98.8 months and <98.8 months (P < 0.001). When we combined groups B and C and set the PFS endpoint as either disease progression or treatment, we found that more than 20% of patients would require treatment within 15 years. CONCLUSIONS: The present study revealed the subsequent course of asymptomatic meningiomas after 5 years of no treatment and demonstrated that 5y-TdT is useful to detect patients who may require treatment.

Radiotherapy Planning System to Measure Tumor Doubling Time in Cervical Cancer.

Tumor doubling time is an important clinical parameter, but it is rarely reported in cervical cancer. We encountered a case in which the tumor doubling time could be measured using a radiotherapy planning device. A woman in her 40s was diagnosed with cervical cancer stage IB1 (squamous cell carcinoma) and refused treatment. One year and five months later, definitive radiation therapy was administered. Magnetic resonance imaging was performed five times before the start of treatment. When the tumor volume was measured using the radiotherapy planning system - RayStation🄬 (RaySearch Laboratories, Stockholm, Sweden) on the T2 sagittal image, the tumor doubling time was 76 days, and the tumor volume had increased exponentially.

SPION and doxorubicin-loaded polymeric nanocarriers for glioblastoma theranostics.

Glioma is a type of cancer with a very poor prognosis with a survival of around 15 months in the case of glioblastoma multiforme (GBM). In order to advance in personalized medicine, we developed polymeric nanoparticles (PNP) loaded with both SPION (superparamagnetic iron oxide nanoparticles) and doxorubicin (DOX). The former being used for its potential to accumulate the PNP in the tumor under a strong magnetic field and the later for its therapeutic potential. The emulsion solvent and evaporation method was selected to develop monodisperse PNP with high loading efficiency in both SPION and DOX. Once injected in mice, a significant accumulation of the PNP was observed within the tumoral tissue under static magnetic field as observed by MRI leading to a reduction of tumor growth rate.

Prediction of tumor doubling time of lung adenocarcinoma using radiomic margin characteristics.

BACKGROUND: Because shape or irregularity along the tumor perimeter can result from interactions between the tumor and the surrounding parenchyma, there could be a difference in tumor growth rate according to tumor margin or shape. However, no attempt has been made to evaluate the correlation between margin or shape features and tumor growth. METHODS: We evaluated 52 lung adenocarcinoma (ADC) patients who had at least two computed tomographic (CT) examinations before curative resection. Volume-based doubling times (DTs) were calculated based on CT scans, and patients were divided into two groups according to the growth pattern (GP) of their ADCs (gradually growing tumors [GP I] vs. growing tumors with a temporary decrease in DT [GP II]). CT radiomic features reflecting margin characteristics were extracted, and radiomic features reflective of tumor DT were selected. RESULTS: Among the 52 patients, 41 (78.8%) were assigned to GP I and 11 (21.2%) to GP II. Of the 94 radiomic features extracted, eccentricity, surface-to-volume ratio, LoG uniformity (σ = 3.5), and LoG skewness (σ = 0.5) were ultimately selected for tumor DT prediction. Selected radiomic features in GP I were surface-to-volume ratio, contrast, LoG uniformity (σ = 3.5), and LoG skewness (σ = 0.5), similar to those for total subjects, whereas the radiomic features in GP II were solidity, energy, and busyness. CONCLUSIONS: This study demonstrated the potential of margin-related radiomic features to predict tumor DT in lung ADCs. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: We found a relationship between margin-related radiomic features and tumor doubling time. WHAT THIS STUDY ADDS: Margin-related radiomic features can potentially be used as noninvasive biomarkers to predict tumor doubling time in lung adenocarcinoma and inform treatment strategies.

[CLINICAL RESULTS OF TWO PATIENTS WITH LATE RECURRENCE OF RENAL CELL CARCINOMA AFTER LONG TERM OBSERVATION WITHOUT TREATMENT].

Two patients with late recurrence of renal cell carcinoma were observed long term without treatment. Case 1 is an 83-year-old woman who underwent right nephrectomy at 57 years of age following a renal tumor diagnosis. Histopathological results revealed clear cell renal cell carcinoma, G2, pT1aN0M0. Pancreatic metastasis developed at age 71, and pancreatic tail excision was performed. A metastatic lesion appeared again at the head of the pancreas at age 74. The patient has been followed by observation only for 9 years without any new lesions. Tumor doubling time calculated from abdominal ultrasonography was 13.3 months.Case 2 is a 91-year-old male. At 78 years of age, right nephrectomy and inferior vena cava tumor embolectomy were performed for renal tumor. Histopathological results revealed clear cell renal cell carcinoma, G2, pT3bN0M0. Left adrenal metastasis appeared at age 84, and the patient has been followed for 7 years without new lesions. Tumor doubling time calculated from abdominal computed tomography (CT) images was 14.1 months.In both patients, no symptoms due to tumor recurrence ever appeared, and their activities of daily living (ADL) were maintained fairly well. In the case of solitary late recurrence in elderly renal cancer patients, observation may be a treatment option that avoids adverse effects and complications caused by treatment. In addition, it appears possible to predict the need for subsequent treatment by calculating the doubling time using several sequential CT images obtained after recurrence. If a new recurrent metastatic lesion appears or if the doubling time during a 2-to 3-year follow-up period is relatively short, however, new treatment should be considered without delay.

Pulmonary sclerosing pneumocytoma demonstrating intratumoral hematoma.

Pulmonary sclerosing pneumocytoma (PSP) is a rare benign neoplasm of the lung that shows a slow growing pattern. Corresponding contrast-enhancements on chest computed tomography (CT) vary widely in both patterns and degrees. However, gross intratumoral radiolucencies, attributable to cyst formation, necrosis, or intratumoral hematoma, were rarely reported in PSP cases. We herein report on a case involving a 61-year-old Japanese women with PSP demonstrating CT-defined intratumoral radiolucency. A chest CT scan revealed a solitary and well-circumscribed nodule that showed a substantial growth over a 7-year period. The tumor was composed of a solid portion visualized with contrast-enhancement and a central radiolucency on a chest CT scan. A positron emission tomography scan revealed high uptake of fluorodeoxyglucose on the solid portion of the tumor, but the radiolucent portion showed negative uptake. The examination of a tumor specimen obtained by a percutaneous core needle biopsy aided in determining a pathological diagnosis of PSP, and the patient subsequently received a right lower lobectomy of the lung. The portion of central radiolucency on the CT scan corresponding to the surgical specimen was pathologically proven to be gross hematoma.

Hepatectomy for rapidly growing solitary liver metastasis from non-small cell lung cancer: a case report.

BACKGROUND: Patients with liver metastasis from non-small lung cancer (NSCLC) usually have multiple metastases at other sites and thus rarely undergo liver surgery. We present a case involving successful resection of rapidly growing liver metastasis from squamous cell carcinoma of the lung. CASE PRESENTATION: A 74-year-old man had undergone left lower lobectomy for squamous cell carcinoma of the lung, which was diagnosed pathologically as stage IA. A computed tomography (CT) scan that was taken 12 months after lung resection showed an irregularly shaped mass lesion (size, 8.3 cm) in segment five of the liver. Retrospectively, the mass was identifiable on CT 6 months before this initial recognition. Although the lesion showed rapid growth, positron emission tomography and brain magnetic resonance imaging ruled out the possibility of other metastatic lesions. Therefore, we performed right hepatectomy 14 months after the initial lung surgery. The patient was pathologically diagnosed with liver metastasis from lung cancer and has remained free from recurrence 41 months after the liver surgery, without receiving any adjuvant chemotherapy. CONCLUSIONS: Although there is no reliable clinical indicator for selecting oligo-recurrence, hepatectomy could be an option for solitary liver metastasis from NSCLC for patients who are in good health.

The tumor doubling time is a useful parameter for predicting the histological type of thymic epithelial tumors.

PURPOSE: We assessed the utility of the tumor doubling time (TDT) for predicting the histological type of thymic epithelial tumors. METHODS: We retrospectively reviewed 130 patients with thymic epithelial tumors who underwent computed tomography two or more times before surgery. The patients were divided into low-risk thymoma (types A, AB and B1), high-risk thymoma (types B2 and B3) and thymic carcinoma (thymic carcinoma and thymic neuroendocrine tumor) groups. In the 96 patients who showed tumor enlargement, the relationship between the histological type and the TDT of the tumor was investigated. RESULTS: The study population included 55 men and 41 women from 26 to 82 years of age. The TDT of the thymic carcinoma group (median 205 days) was significantly shorter in comparison to the low-risk thymoma (median 607 days) and high-risk thymoma (median 459 days) groups. No significant differences were observed between the low-risk thymoma and high-risk thymoma groups. When we set the cutoff time for differentiating thymic carcinoma group from thymoma at 313 days, the sensitivity and specificity were 83.8% and 82.1%, respectively. CONCLUSIONS: The TDT is a useful parameter for differentiating between thymoma and thymic carcinoma group.

Tumor doubling time predicts response to sorafenib in radioactive iodine-refractory differentiated thyroid cancer.

Sorafenib has emerged as an effective therapeutic option for radioactive iodine (RAI)-refractory, locally advanced or metastatic differentiated thyroid cancer (DTC). We investigated the efficacy and safety of sorafenib treatment in a real-world setting and unveil predictive markers of responsiveness to sorafenib. The treatment response, progression-free survival (PFS), overall survival, and adverse events (AEs) of sorafenib-treated RAI-refractory, locally advanced or metastatic DTC patients at three institutes were retrospectively reviewed, and their tumor doubling time was calculated by three investigators. Total eighty-five patients were treated with sorafenib, and seven patients discontinued sorafenib due to AEs before the first tumor assessment. The median PFS was 14.4 months, and the objective response rate was 10.3% in 78 patients who were able to evaluate the tumor response. Age, sex, histologic type, tumor location, RAI avidity, or the presence of FDG-PET uptake did not affect PFS. However, smaller tumor size (≤1.5 cm) of the target lesions in lung showed better PFS (hazard ratio [HR] 0.39, p = 0.01), and tumors with the shortest doubling time (≤6 months) had worse outcome (HR 2.70, p < 0.01). Because of AEs, dose reductions or drug interruptions were required in 64% of patients, and eventually, 23% of patients discontinued sorafenib permanently. The most common AE was hand-foot skin reaction (HFSR). Patients with severe HFSR showed better PFS, but there were no statistical significance (HR 0.65, p = 0.05). In conclusion, small tumor size and long doubling time of each target lesion can be a prognostic marker to predict the responsiveness to sorafenib in RAI-refractory DTC patients.

Solid component tumor doubling time is a prognostic factor in non-small cell lung cancer patients.

BACKGROUND: Recently, several reports investigating tumor doubling times (TDTs) in lung cancer have demonstrated that lung cancer patients with shorter TDTs have poor prognoses. Although data have shown that the solid component of a tumor is clinically more important, relationships between solid component TDTs and lung cancer prognoses remain unclear. METHODS: To evaluate relationships between TDT and survival, we retrospectively evaluated 231 patients who underwent surgical resection for non-small cell lung cancer. The TDTs of whole and solid components were calculated using preoperative thin-slice chest computed tomography scans with a cut-off of 400 d between scans. RESULTS: Patients with short TDTs (< 400 d) both in the solid and whole components had poor prognoses. Among pathological stage I patients (n = 176), short solid component TDT (< 400 d) significantly influenced prognosis only in pathological stage IB patients. Moreover, we found that patients with shorter solid component TDTs had significantly worse prognosis compared with patients who showed shorter whole component TDTs. CONCLUSIONS: Short solid component TDTs (< 400 d) could be a poor prognostic indicator for non-small cell lung cancer patients undergoing surgical resection; furthermore, clinicians should pay particularly close attention to cases with rapid growth of the solid tumor component.