Assessment for the timing of comprehensive genomic profiling tests in patients with advanced solid cancers.

Comprehensive genomic profiling (CGP) tests have been covered by public insurance in Japan for patients with advanced solid tumors who have completed or are completing standard treatments or do not have them. Therefore, genotype-matched drug candidates are often unapproved or off-label, and improving clinical trial access is critical, involving the appropriate timing of CGP tests. To address this issue, we analyzed the previous treatment data for 441 patients from an observational study on CGP tests discussed by the expert panel at Hokkaido University Hospital between August 2019 and May 2021. The median number of previous treatment lines was two; three or more lines accounted for 49%. Information on genotype-matched therapies was provided to 277 (63%). Genotype-matched clinical trials were ineligible because of an excess number of previous treatment lines or use of specific agents were found in 66 (15%) patients, with the highest proportion in breast and prostate cancers. Many patients met the exclusion criteria of one to two or more treatment lines across cancer types. In addition, previous use of specific agents was a frequent exclusion criterion for breast, prostate, colorectal, and ovarian cancers. The patients with tumor types with a low median number (two or fewer) of previous treatment lines, including most rare cancers, primary unknown cancers, and pancreatic cancers, had significantly fewer ineligible clinical trials. The earlier timing of CGP tests may improve access to genotype-matched clinical trials, with their proportion varying by cancer type. Each relevant society needs to advocate the desirable timing of CGP testing nationwide.

Patterns and predictors of site-specific recurrence in cervical cancer after radical hysterectomy.

AIM: This study examines patterns and predictors of site-specific recurrence to explore the causes of local recurrence of cervical cancer. METHODS: Radical hysterectomy was performed in 121 patients (stage IB-IIB). Nerve-sparing was performed whenever possible. The first recurrence in local, regional, and distant areas was examined. We investigated the possibility of nerve involvement in local recurrence, focusing on paravaginal tissues containing the pelvic plexus. We provide Supporting Information on local recurrence in the paravaginal area. RESULTS: Local recurrence was an independent event from regional or distant recurrence. Local recurrence was seen only in high-risk patients, while regional and distant recurrences were not or less related to the risk category. The independent risk factors by logistic regression for local, regional, and distant recurrence were parametrial invasion, vaginal invasion, and lymph node metastasis, respectively. Local recurrence showed a comparable or more significant negative impact on survival than distant recurrence. Among seven patients with local recurrences, five had a recurrence in the paravagina. The rate of paravaginal recurrence was one in 76 early-stage and four in 45 locally advanced diseases. Four sites of paravaginal recurrence occurred on the nerve-sparing side and two on the non-nerve-sparing side. Supporting Information demonstrated histological evidence of perineural spread into the pelvic plexus and perineural invasion of the primary tumor. CONCLUSIONS: A high percentage of local recurrences are in paravaginal tissue containing the pelvic plexus. The causal association of nerve-sparing surgery and perineural invasion with local recurrence needs to be investigated in large prospective studies.

Clinical significance of comprehensive genomic profiling tests covered by public insurance in patients with advanced solid cancers in Hokkaido, Japan.

BACKGROUND: Comprehensive cancer genomic profiling has been used recently for patients with advanced solid cancers. Two cancer genomic profiling tests for patients with no standard treatment are covered by Japanese public health insurance since June 2019. METHODS: We prospectively analyzed data of 189 patients with solid cancers who underwent either of the two-cancer genomic profiling tests at Hokkaido University Hospital and its liaison hospitals and whose results were discussed in molecular tumor board at Hokkaido University Hospital between August 2019 and July 2020. RESULTS: All 189 patients had appropriate results. Actionable gene alterations were identified in 93 patients (49%). Frequent mutations included PIK3CA (12%) mutation, BRCA1/2 alteration (7%), ERBB2 amplification (6%) and tumor mutation burden-High (4%). The median turnaround time from sample shipping to acquisition by the expert panel was 26 days. Although 115 patients (61%) were provided with information for genotype-matched therapies, only 21 (11%) received them. Notably, four of eight patients below the age of 20 years were provided information for genotype-matched therapies, and three received them. Their response rates and disease control rates were 29% and 67%, respectively. Most patients who did not undergo the genotype-matched therapies were provided information for only investigational drugs in phases I and II at distant clinical trial sites in central Japan. Twenty-six patients were informed of suspected germline findings, while 11 patients (42%) received genetic counseling. CONCLUSIONS: The publicly reimbursed cancer genomic profilings may lead to the modest but favorable therapeutic efficacy of genotype-matched therapy for solid cancer patients with no standard therapy. However, poor access to genotype-matched therapy needs to be resolved.

The disease sites of female genital cancers of BRCA1/2-associated hereditary breast and ovarian cancer: a retrospective study.

Disease sites of female genital tract cancers of BRCA1/2-associated hereditary breast and ovarian cancer (HBOC) are less understood than non-hereditary cancers. We aimed to elucidate the disease site distribution of genital cancers in women with the germline BRCA1 and BRCA2 pathogenic variants (BRCA1+ and BRCA2+) of HBOC. For the primary disease site, the proportion of fallopian tube and peritoneal cancer was significantly higher in BRCA2+ (40.5%) compared with BRCA1+ (15.4%) and BRCA- (no pathogenic variant, 12.8%). For the metastatic site, the proportion of peritoneal dissemination was significantly higher in BRCA1+ (71.9%) than BRCA- (55.1%) and not different from BRCA2+ (71.4%). With one of the most extensive patients, this study supported the previous reports showing that the pathogenic variants of BRCA1/2 were involved in the female genitalia's disease sites.

The difficulty to diagnose cervical cancer developing in the perinatal period with the first-trimester cytology: A retrospective study.

AIM: Cytological cervical cancer screening for pregnant women is routinely performed and still plays an essential role in Japan because of the considerably low rate of human pappillomavirus (HPV) vaccination. Though almost all pregnant women undergo cytological screening at their first trimester, we experienced invasive cervical cancers (ICC) diagnosed during pregnancy or postpartum period. We investigated the characteristics of perinatally diagnosed ICCs to clarify the difficulty in diagnosis during the pregnancy. METHODS: We retrospectively reviewed the clinical data on ICC diagnosed during pregnancy or within 1 year after delivery from 2010 to 2018 at Hokkaido University Hospital. RESULTS: We identified 18 ICC patients, and the median follow-up period was 46.5 months. Among eight patients with negative for intraepithelial lesion or malignancy (NILM), the mean duration to reach ICC diagnosis was 10.7 months, seven had stage IB1 or worse, and one was dead. On the other hand, among 10 women with abnormal cytology, the mean duration for diagnosis was 1.4 months, and 6 had stage IB1 or worse, and 1was dead. In terms of the timing of the final diagnosis, 8 were during pregnancy and 10 in the postpartum periods. Among eight pregnant patients, three resulted in a preterm delivery (33, 34, and 35 gestational weeks), and four terminated their pregnancies. One decided to continue the pregnancy until the term period. We performed conization in one patient and hysterectomy in seven. CONCLUSION: A part of cytological examinations of pregnant women may result in presumed false-negative or underestimation, which keeps them away from the additional examination to find ICC.

L1CAM Predicts Adverse Outcomes in Patients with Endometrial Cancer Undergoing Full Lymphadenectomy and Adjuvant Chemotherapy.

BACKGROUND: L1 cell adhesion molecule (L1CAM) has been established as an important predictor of poor survival of early-stage endometrial cancer patients. We investigated whether L1CAM remains a significant predictor of poor survival of patients with advanced-stage endometrial cancer undergoing extensive surgical staging and adjuvant chemotherapy. METHODS: We prepared tissue microarray (TMA) from surgical tissue specimens of 161 endometrial cancer patients who underwent full lymphadenectomy combined with adjuvant chemotherapy for patients at risk for recurrence, and evaluated expression of L1CAM using immunohistochemistry. The correlation between L1CAM positivity and clinicopathological factors and the prognostic significance of L1CAM expression was investigated. RESULTS: Among 161 cases who had a follow-up duration of over 3 years, 48 cases (29.8%) showed positive staining for L1CAM. L1CAM positivity was significantly correlated with non-endometrioid histology (p < 0.0001), vascular invasion (p = 0.0157), and positive cytology (p = 0.005), and was a significant predictor of poor survival among advanced-stage patients, but not early-stage patients in our cohort. L1CAM-positive patients showed a higher recurrence rate and frequency of distant failure than L1CAM-negative patients. Multivariate analysis revealed that para-aortic lymph node metastasis (PANM) and L1CAM positivity were independent predictors of poor survival. Overall survival can be stratified into three groups by the combination of PANM and L1CAM positivity. CONCLUSION: L1CAM is an independent predictor of poor survival in endometrial cancer patients undergoing full lymphadenectomy and adjuvant chemotherapy, thus indicating that L1CAM can be clinically used as a biomarker to identify those patients at increased risk of recurrence.

Risk factors for lymph node metastasis of ovarian, fallopian tube and primary peritoneal cancer in hereditary breast and ovarian cancer syndrome.

BACKGROUND: To establish an individualized surgical strategy for lymphadenectomy in ovarian cancer patients with the germline BRCA1 and BRCA2 pathogenic variants (BRCA1+ and BRCA2+), we investigated the clinicopathological characteristics that are involved in the increased risk of lymph node metastasis. METHODS: We retrospectively reviewed the data of Japanese women registered in the database of the Japanese Hereditary Breast and Ovarian Cancer Consortium, who underwent BRCA1 and BRCA2 genetic testing. RESULTS: We evaluated the predictors of lymph node metastasis in all patients with the information of age at the diagnosis, disease site, histological subtype, 2014 FIGO stage, personal breast cancer history and family history; 233, 153 and 32 patients in the BRCA- (no pathogenic variant), BRCA1+ and BRCA2+ groups, respectively. The prevalence of lymph node metastasis was not markedly different between BRCA- (20.0%), BRCA1+ (18.4%) and BRCA2+ (26.2%). Multivariate analysis revealed an absence of a family history of ovarian cancer as an independent predictor for an increased risk of lymph node metastasis in BRCA1+, and the prevalence of lymph node metastasis was 11.7 and 42.0% in the groups with and without a family history of ovarian cancer, respectively. This subgroup without a family history of ovarian cancer did not show any correlation with a particular variant of BRCA1, including two common variants of c.188 T > A and c.2800C > T. CONCLUSIONS: This study suggested that certain genetic factors related to the penetrance of hereditary breast and ovarian cancer syndrome altered the frequency of lymph node metastasis in BRCA1+ ovarian cancer, and family history may be useful to personalize the indication of lymphadenectomy.

Four versus six chemotherapy cycles in endometrial carcinoma with a high risk of recurrence: a retrospective study.

OBJECTIVE: This study compared the survival outcomes and the incidence of chemotherapy-related adverse events in endometrial cancer patients who received four and six cycles of adjuvant chemotherapy to examine the optimal number of adjuvant chemotherapy cycles. METHODS: A total of 112 patients with endometrial cancer with a high risk of recurrence were retrospectively enrolled; 46 patients received four cycles and 66 received six cycles of adjuvant chemotherapy. Between-group differences of overall survival, disease-free survival, hematological and non-hematological toxicities were analyzed. Baseline patient's background differences were assessed with inverse probability of treatment weighting using propensity score. RESULTS: Overall and disease-free survivals between the two groups were not significantly different. Paclitaxel + carboplatin, every 3-4 weeks was the most frequently used chemotherapy regimen in both groups. Patients in the six-cycle chemotherapy group developed neutropenia G4 or febrile neutropenia more frequently than those in the four-cycle group; odds ratio (95% confidence interval) is 4.07 (1.51-10.96). Peripheral sensory neuropathy was the most frequently observed non-hematological toxicity; the incidence of peripheral sensory neuropathy was not significantly different between four- and six-cycle chemotherapy group, P = 0.832. The result was same in the subgroup analysis in patients who received TC regimen, P = 0.455. CONCLUSION: This study implies a possible benefit of fewer cycles of adjuvant chemotherapy in endometrial cancer patients with a high risk of recurrence because of the lower incidence of hematological toxicities without impairing survival outcomes.

Tailored radical hysterectomy for locally advanced cervical cancer.

OBJECTIVE: The survival and prognostic factors for locally advanced cervical cancer treated with nerve-sparing Okabayashi-Kobayashi radical hysterectomy have not been elucidated. We aimed to evaluate the oncological outcomes of those patients after radical hysterectomy with adjuvant chemotherapy. METHODS: This retrospective cohort study was conducted from January 2002 to December 2011. Treatment was conducted at a single tertiary center in northern Japan. We used the Okabayashi-Kobayashi radical hysterectomy with lymphadenectomy. We applied unilateral nerve preservation for stage IIA/IIB cancer if there was a one-sided extension of the disease outside the cervix. Indication for adjuvant therapy was based on Sedlis criteria. High-risk was defined as evidence of lymph node metastasis, pathological parametrial invasion, and a positive/close surgical margin. The choice of adjuvant therapy was chemotherapy which consisted of paclitaxel and cisplatin. RESULTS: The study included 76 early-stage IB1 (≤4 cm) and IIA1 cervical cancer and 45 locally advanced stage IB2 (>4 cm), IIA2, and IIB disease treated consecutively. The median follow-up was 106 (range: 6-203) months. There were 18 (15%) patients with recurrence, with five of 76 in the early-stage (7%) and 13 of 45 in the locally advanced disease (29%) (P<0.001). For locally advanced cervical cancer, pT classification (P<0.001), lymph node metastasis (P=0.007), and histology (P=0.05) were associated with locoregional recurrence. The five-year locoregional recurrence rate in the locally advanced disease was 20% and 5% in the early-stage disease (P=0.01). The five-year disease-free survival in the locally advanced cervical cancer was 71% and 93% in the early-stage disease (P<0.001). The overall survival in locally advanced disease depended on the adeno-type histology and lymph node metastasis. CONCLUSION: The tailored use of nerve-sparing Okabayashi-Kobayashi radical hysterectomy with adjuvant chemotherapy based on tumor histology and lymph node metastasis may be a possible option as a treatment of locally advanced cervical cancer in selected patients.

Role of ADP receptors on platelets in the growth of ovarian cancer.

We investigated the effect of platelets on ovarian cancer and the role of adenosine diphosphate (ADP) receptors (P2Y12 and P2Y1) on platelets in the growth of primary ovarian cancer tumors. We showed that in murine models of ovarian cancer, a P2Y12 inhibitor (ticagrelor) reduced tumor growth by 60% compared with aspirin and by 75% compared with placebo. In P2Y12-/- mice, the growth of syngeneic ovarian cancer tumors was reduced by >85% compared with wild-type (WT) mice. In contrast, there was no difference in tumor growth between P2Y1-/- and WT mice. Reconstitution of hematopoiesis in irradiated P2Y12-/- mice by hematopoietic progenitor cells from WT mice (WT→P2Y12-/-) restored tumor growth in P2Y12-/- mice. Finally, knockdown of ecto-apyrase (CD39) on ovarian cancer cells increased tumor growth in tumor-bearing mice. Although in the absence of platelets, ADP, the P2Y12 inhibitor, recombinant apyrase, or knockdown of CD39 did not affect cancer cell proliferation, in the presence of platelets, the P2Y12 inhibitor and recombinant apyrase reduced and knockdown of CD39 increased platelet-enhanced cancer cell proliferation. These results suggest that P2Y12 on platelets and ADP concentration at the interface between cancer cells and platelets affect the growth of primary ovarian cancer tumors in mice. If additional studies in mice and in pilot human trials confirm our results, inhibition of P2Y12 might be a new therapeutic option that can be used in adjuvant to the traditional surgery and chemotherapy in patients with ovarian cancer.

Molecular-targeted therapies and precision medicine for endometrial cancer.

The overall survival rate of patients with early-stage endometrial cancer is relatively high; however, there are few treatment options for patients with advanced or recurrent endometrial cancer, and the prognosis of such patients remains poor. Recent progress in molecular-targeted therapies demonstrated that they have the potential to improve the long-term survival of cancer patients with appropriate biomarkers. However, the median progression-free survival of patients who received single-agent molecular-targeted therapy was <5 months, and the development of molecular-targeted therapies for endometrial cancer patients is urgently needed. This review highlights the previous efforts, including antiangiogenesis therapy, PI3K/AKT/mTOR pathway inhibitor treatment and epidermal growth factor receptor inhibitor treatment and reports on ongoing phase 2 clinical trials, including immune checkpoint inhibitor and PARP inhibitor. We also summarized the genetic background of endometrial cancer according to The Cancer Genome Atlas data and considered the theoretical background for future efforts to prolong the survival of patients with refractory endometrial cancer and for other interesting challenges.

Prediction of anti-angiogenesis escape.

Many clinical trials have demonstrated the benefit of anti-angiogenesis therapy in the treatment of gynecologic cancer. However, these benefits have often been in terms of progression-free rather than overall survival and in some cases, the magnitude of benefit demonstrated in the pivotal phase 3 trials has been disappointing when compared with the percentage of patients who responded in earlier phase 2 trials. Two potential explanations for this are the current inability to stratify patients according to chance of benefit and the development of resistance mechanisms within the tumor. In this article, we review the prediction of response and the proposed resistance and escape mechanisms involved in anti-angiogenesis therapy, including the up-regulation of alternative proangiogenic pathways, vascular co-option, and resistance to hypoxia. These insights may offer a personalized strategy for anti-angiogenesis therapy and help us to consider the best selection of other therapies that should be combined with anti-angiogenesis therapy to improve the outcome of patients with gynecologic cancer.

Human papillomavirus type 16 sequence variation in concurrent vulvar and penile carcinoma in a married couple.

We encountered an elderly married couple with concurrent vulvar and penile carcinoma with an Asian variant of human papillomavirus type 16. Asian variants might have an elevated risk of concurrent external genital carcinomas of a male and a female, and analysis of human papillomavirus variants might be important to understand the mechanism of carcinogenesis.

microRNA 31 functions as an endometrial cancer oncogene by suppressing Hippo tumor suppressor pathway.

BACKGROUND: We aimed to investigate whether MIR31 is an oncogene in human endometrial cancer and identify the target molecules associated with the malignant phenotype. METHODS: We investigated the growth potentials of MIR31-overexpressing HEC-50B cells in vitro and in vivo. In order to identify the target molecule of MIR31, a luciferase reporter assay was performed, and the corresponding downstream signaling pathway was examined using immunohistochemistry of human endometrial cancer tissues. We also investigated the MIR31 expression in 34 patients according to the postoperative risk of recurrence. RESULTS: The overexpression of MIR31 significantly promoted anchorage-independent growth in vitro and significantly increased the tumor forming potential in vivo. MIR31 significantly suppressed the luciferase activity of mRNA combined with the LATS2 3'-UTR and consequently promoted the translocation of YAP1, a key molecule in the Hippo pathway, into the nucleus. Meanwhile, the nuclear localization of YAP1 increased the transcription of CCND1. Furthermore, the expression levels of MIR31 were significantly increased (10.7-fold) in the patients (n = 27) with a high risk of recurrence compared to that observed in the low-risk patients (n = 7), and this higher expression correlated with a poor survival. CONCLUSIONS: MIR31 functions as an oncogene in endometrial cancer by repressing the Hippo pathway. MIR31 is a potential new molecular marker for predicting the risk of recurrence and prognosis of endometrial cancer.

Distribution of lymph node metastasis sites in endometrial cancer undergoing systematic pelvic and para-aortic lymphadenectomy: a proposal of optimal lymphadenectomy for future clinical trials.

PURPOSE: The aim of this study was to demonstrate the precise mapping of lymph node metastasis (LNM) sites in endometrial cancer. METHODS: A total of 266 patients who underwent primary radical surgery including systematic pelvic and para-aortic lymphadenectomy for endometrial cancer from 1993 to 2010 were enrolled in this study. We removed lymph nodes from the femoral ring to the para-aortic node up to the level of renal veins. We analyzed the distribution of positive-node sites according to their anatomical location. RESULTS: Overall, 42 of 266 patients (15.8 %) showed LNM. The median number of nodes harvested was 62.5 (range 40-119) in pelvic nodes (PLN), and 20 (range 3-47) in para-aortic nodes (PAN). Among 42 cases with positive-nodes, 16 cases (38.1 %) showed positive PLN alone, 7 cases (16.7 %) in PAN alone, and 19 cases (45.2 %) in both PLN and PAN. The most prevalent site of positive-nodes was PAN (9.8 %) followed by obturator nodes (9.4 %), internal iliac nodes (7.1 %), and common iliac nodes (5.6 %). Six of 19 cases (31.6 %) of positive PAN above the inferior mesenteric artery (IMA) showed negative PAN below IMA. Metastasis to the deep inguinal nodes was found to be extremely rare (0.38 %). Single-site LNM was the most frequently observed in obturator nodes, followed by PAN above IMA. CONCLUSION: Routine resection of deep inguinal nodes is not recommended, whereas para-aortic lymphadenectomy should be extended up to the level of renal veins for endometrial cancer.

A low-risk group for lymph node metastasis is accurately identified by Korean gynecologic oncology group criteria in two Japanese cohorts with endometrial cancer.

OBJECTIVE: The Korean Gynecologic Oncology Group (KGOG) recently proposed new pre-operative criteria to identify a low-risk group for lymph node metastasis in endometrial cancer. The aim of this study was to test whether the good performance of the criteria can be reproducible in diverse clinical settings. METHODS: From two Japanese hospitals, 319 patients with endometrial cancer who underwent systemic lymphadenectomy were retrospectively reviewed. In one hospital, para-aortic lymphadenectomy was routinely performed, but it was selectively performed in the other hospital. The performance of the criteria was determined by adjusting the false-negative rate (FNR) at the given prevalence of nodal metastasis of 10% using Bayes' theorem. RESULTS: Nodal metastasis rate of the study population was 12.9%. The KGOG low-risk criteria identified 181 of 319 patients as a low-risk group (51%), and three false-negative cases were found (1.9%). Despite a significant difference in the nodal metastasis rate (18.2% and 8.8%, P=.012) and the surgical policy for para-aortic lymphadenectomy (100% and 48.9%, P<.001) between the two hospitals, KGOG criteria consistently showed a very low adjusted FNR at the prevalence of 10% in both hospitals (1.8% vs. 1.1%, respectively). Among the entire study population, the adjusted FNR was 1.4% (95% confidence interval, .5% to 4.3%), which was similar to the FNR of 1.3% in our previous study. CONCLUSION: The KGOG low-risk criteria accurately identified a low-risk group for lymph node metastasis with acceptable false negativity regardless of diverse clinical settings.

Combination therapy with bevacizumab and a CCR2 inhibitor for human ovarian cancer: An in vivo validation study.

BACKGROUND: Anti-angiogenic therapy with bevacizumab (BEV), an anti-VEGF antibody, plays a critical role in the treatment of ovarian cancer. However, despite an encouraging initial response, most tumors become resistant to BEV over time, and a new strategy that enables sustainable treatment using BEV is therefore needed. METHODS: To overcome the resistance to BEV in patients with ovarian cancer, we performed a validation study of combination therapy with BEV (10 mg/kg) and the CCR2 inhibitor BMS CCR2 22 (20 mg/kg) (BEV/CCR2i) using 3 consecutive patient-derived xenografts (PDXs) of immunodeficient mice. RESULTS: BEV/CCR2i demonstrated a significant effect of growth suppression in the BEV-resistant serous PDX and BEV-sensitive serous PDX compared with BEV (30.4% after the second cycle and 15.5% after the first cycle, respectively), and treatment cessation did not attenuate this effect. Tissue clearing and immunohistochemistry with an anti-α-SMA antibody suggested that BEV/CCR2i suppressed angiogenesis from the host mice more than BEV. In addition, human CD31 immunohistochemistry revealed that BEV/CCR2i decreased microvessels originating from the patients to a significantly greater degree than BEV. Regarding the BEV-resistant clear cell PDX, the effect of BEV/CCR2i was unclear during the first five cycles, but the following two cycles of increased-dose BEV/CCR2i (CCR2i 40 mg/kg) significantly suppressed tumor growth compared with BEV (28.3%) by inhibiting the CCR2B-MAPK pathway. CONCLUSIONS: BEV/CCR2i showed a sustained anticancer immunity-independent effect in human ovarian cancer that was more significant in serous carcinoma than in clear cell carcinoma.

Distribution of human papilloma virus genotypes and treatment outcomes in definitive radiotherapy for cervical cancer.

Most oncogenic human papilloma virus (HPV) genotypes stratify into two species, α-7 HPV and α-9 HPV. There are several studies that evaluate the relationship between HPV species and treatment outcomes and reports that HPV species is prognostic. The HPV genotyping was conducted using biopsy specimens which had been stored in these studies. We conducted the study using the HPV test performed by cytology specimens which is less invasive and more useful in clinical settings. This study enrolled 46 patients who received HPV genotyping before the definitive radiotherapy. The results of the HPV genotyping were classified into HPVα-7, HPVα-9 and negatives. Of the 46 patients, 10 were positive for HPVα-7, 21 positive for HPVα-9 and 15 were negative. The median follow-up period was 38 months (range 4-142). The HPVα-7, HPVα-9 and negative groups showed the 3-year overall survival (OS; 59.3%, 80.4% and 72.2% [P = 0.25]); local control (LC; 67.5%, 81% and 80% [P = 0.78]); pelvic control (PC) (50%, 81% and 72.7% [P = 0.032]); pelvic lymph node (PLN) control (78.7%, 95% and 92.3% [P = 0.012]); distant metastasis free (DMF) survival (50%, 75.4% and 42.8% [P = 0.098]); and progression free survival (PFS) rate of patients (30%, 66.7% and 38.9% [P = 0.085]), respectively. Patients with HPVα-7 showed statistically significant poorer PC than the HPVα-9 group, in multivariate analysis. This result is consistent with previous studies for HPV positive patients. The HPV negativity rate was higher in this study than in other studies and further work on this may be needed for clinical use.

Clinical efficacy of paclitaxel/cisplatin as an adjuvant chemotherapy for patients with cervical cancer who underwent radical hysterectomy and systematic lymphadenectomy.

BACKGROUND AND OBJECTIVES: The aim of this study was to compare the clinical efficacy of paclitaxel/cisplatin (TP) as an adjuvant chemotherapy to adjuvant radiotherapy (RT) after radical hysterectomy and systematic lymphadenectomy for patients with cervical cancer. METHODS: A total of 125 patients with early-stage cervical cancer, who underwent radical hysterectomy, and received adjuvant therapy due to recurrent risk factors were retrospectively analyzed. Forty-nine patients were treated with RT, and 32 received paclitaxel/cisplatin (TP) for three to six cycles at 4-week interval. Survival and postoperative complications were compared between two modalities. RESULTS: There was no significant difference of 3-year disease-free survival between two groups (P = 0.23), while significantly better 3-year overall survival in TP group than RT group (P = 0.02). Seven of 32 patients (21.9%) treated with adjuvant TP, 16 of 49 patients (32.7%) treated with RT showed disease recurrence. Median of survival time after recurrence in RT group and TP group was 8.5 months, 12.0 months, respectively. Postoperative bowel obstruction was significantly more frequent in the RT group compared to the TP group (P = 0.01). CONCLUSIONS: Postoperative chemotherapy using TP might be more beneficial for survival than adjuvant RT and can reduce postoperative complications for cervical cancer patients treated with radical hysterectomy.