Prognostic Value of Body Composition and Systemic Inflammatory Markers in Patients with Locally Advanced Cervical Cancer Following Chemoradiotherapy.

Background: Abnormal changes in body composition and systemic inflammation response have been associated with poor survival of cancer patients. Our study was to explore the prognostic value of the association between body composition indicators and systemic inflammation markers among patients with locally advanced cervical cancer (LACC) who underwent concurrent chemoradiotherapy (CCRT). Methods: We retrospectively reviewed medical records of LACC patients treated between 2016 and 2019. Subcutaneous, visceral and intra-muscular adipose index (SAI, VAI and IMAI) and skeletal muscle index (SMI) were derived from computed tomography (CT). Kaplan-Meier analysis and Univariate and multivariate Cox analyses were used to evaluate the survival. A nomogram was constructed to assess the prognostic value. Results: The study included 196 patients treated with CCRT. According to multivariable Cox analyses, IIIC1r (P = 0.045), high systemic immune-inflammation index (SII) (P = 0.004), sarcopenia (P = 0.008), high SAI (P = 0.016) and high VAI (P = 0.001) were significantly risk factors for overall survival (OS). Kaplan-Meier analysis showed that patients with low lymphocyte-to-monocyte ratio (LMR) and sarcopenia had longer OS than those with high LMR and sarcopenia (P = 0.023). The high neutrophil-to-lymphocyte ratio (NLR) in non-sarcopenic patients showed better survival (P = 0.022). Low VAI (P = 0.019) or low IMAI (P = 0.019) combined with low SII had a favorable OS. Low LMR combined with low SAI was associated with longer OS (P = 0.022). The calibration plots of nomogram predicting the 3-year and 5-year OS rates were close to the ideal models. Conclusion: Inflammation factors were closely associated with abnormal muscle and fat distribution. The combined prognostic value of body composition indicators and systemic inflammation markers was reliable in predicting survival for LACC patients.

Comparing dosimetric and cancer control outcomes after intensity-modulated radiation therapy and tomotherapy for advanced cervical cancer.

Concurrent chemoradiation therapy (CCRT) is the standard treatment for locally advanced cervical cancer. The present study aimed to compare the therapeutic responses, toxicities and dosimetric parameters between intensity-modulated radiation therapy (IMRT) and tomotherapy (TOMO) in patients with advanced cervical cancer. This retrospective study included 310 patients with stage IIB-IIIB cervical cancer who underwent CCRT, with 155 patients in each group. Intracavitary brachytherapy was performed after a course of external beam radiation therapy (EBRT), or in the last week of pelvic EBRT. The treatment planning aim at point A (defined as a reference location 2 cm above the vaginal fornix and 2 cm beside the mid axis of the uterus) was >85 Gy in an equivalent dose at 2 Gy. There was no statistical difference with regard to clinicopathological characteristics between the two groups (P>0.05). Improved dose conformity and dose homogeneity (P<0.05) were observed in TOMO planning. TOMO provided more efficacious critical organ sparing than IMRT when assessing the percentage of normal tissue receiving at least 20 Gy (V20) for the bladder, the percentage of normal tissue receiving at least 40 Gy (V40) for the femoral head, and the V40 and V20 for the rectum (P<0.05). TOMO demonstrated a greater ability to protect the ovary (P<0.05). The acute radiation toxicity of proctitis and leukopenia were significantly lower in the TOMO group (P<0.05). The chronic radiation toxicity of radiation enterocolitis and cystitis was lower in the TOMO group (P<0.05). Thus, TOMO provided better critical organ sparing than IMRT. The radiation toxicities were acceptable. Therefore, TOMO appears to be a good option for the treatment of stage IIB-IIIB cervical cancer.

Dosimetric predictors and Lyman normal tissue complication probability model of hematological toxicity in cervical cancer patients with treated with pelvic irradiation.

PURPOSE: To identify dosimetric parameters associated with acute hematological toxicity (HT) and identify the corresponding normal tissue complication probability (NTCP) model in cervical cancer patients receiving helical tomotherapy (Tomo) or fixed-field intensity-modulated radiation therapy (ff-IMRT) in combination with chemotherapy, that is, concurrent chemoradiotherapy (CCRT) using the Lyman-Kutcher-Burman normal tissue complication probability (LKB-NTCP) model. METHODS: Data were collected from 232 cervical cancer patients who received Tomo or ff-IMRT from 2015 to 2018. The pelvic bone marrow (PBM) (including the ilium, pubes, ischia, acetabula, proximal femora, and lumbosacral spine) was contoured from the superior boundary (usually the lumbar 5 vertebra) of the planning target volume (PTV) to the proximal end of the femoral head (the lower edge of the ischial tubercle). The parameters of the LKB model predicting ≥grade 2 hematological toxicity (Radiation Therapy Oncology Group [RTOG] grading criteria) (TD50 (1), m, and n) were determined using maximum likelihood analyses. Univariate and multivariate logistic regression analyses were used to identify correlations between dose-volume parameters and the clinical factors of HT. RESULTS: In total, 212 (91.37%) patients experienced ≥grade 2 hematological toxicity. The fitted normal tissue complication probability model parameters were TD50 (1) = 38.90 Gy (95%CI, [36.94, 40.96]), m = 0.13 (95%CI [0.12, 0.16]), and n = 0.04 (95%CI [0.02, 0.05]). Per the univariate analysis, the NTCP (the use of LKB-NTCP with the set of model parameters found, p = 0.023), maximal PBM dose (p = 0.01), mean PBM dose (p = 0.021), radiation dose (p = 0.001), and V16-53 (p < 0. 05) were associated with ≥grade 2 HT. The NTCP (the use of LKB-NTCP with the set of model parameters found, p = 0.023; AUC = 0.87), V16, V17, and V18 ≥ 79.65%, 75.68%, and 72.65%, respectively (p < 0.01, AUC = 0.66∼0.68), V35 and V36 ≥ 30.35% and 28.56%, respectively (p < 0.05; AUC = 0.71), and V47 ≥ 13.43% (p = 0.045; AUC = 0.80) were significant predictors of ≥grade 2 hematological toxicity from the multivariate logistic regression analysis. CONCLUSIONS: The volume of the PBM of patients treated with concurrent chemoradiotherapy and subjected to both low-dose (V16-18 ) and high-dose (V35,36 and V47 ) irradiation was associated with hematological toxicity, depending on the fractional volumes receiving the variable degree of dosage. The NTCP were stronger predictors of toxicity than V16-18 , V35, 36 , and V47 . Hence, avoiding radiation hot spots on the PBM could reduce the incidence of severe HT.

Postoperative adjuvant chemotherapy combined with intracavitary brachytherapy achieved the equivalent survival compared with concurrent chemoradiotherapy in cervical cancer patients with intermediate-risk.

OBJECTIVES: The current study was aimed to evaluate the efficacy and toxicity of postoperative adjuvant chemotherapy (CT) combined with intracavitary brachytherapy (ICRT) in cervical cancer patients with intermediate-risk. METHODS: We analyzed the medical records of 558 patients who were submitted to radical surgery for Stage IB-IIA cervical cancer. A total of 172 of those 558 patients were considered intermediate-risk according to the GOG criteria. Among those 172 patients, 102 were subjected to CT combined with ICRT (CT+ICRT) and the remaining 70 patients were treated with concurrent chemoradiation (CCRT). The 3-year disease free survival (DFS), overall survival (OS), and complications of each group were evaluated and analyzed. RESULTS: No significant difference was observed in 3-year DFS or OS of the patients submitted to CT+ICRT and CCRT. Importantly, the frequencies of grade III to IV acute complications were significantly higher in patients submitted to CCRT than in those treated with CT+ICRT (Hematologic, P = 0.016; Gastrointestinal, P = 0.041; Genitourinary, P = 0.019). Moreover, the frequencies of grade III-IV late complications in patients treated with CCRT were significantly higher compared with CT+ICRT-treated patients (Gastrointestinal, P = 0.026; Genitourinary, P = 0.026; Lower extremity edema, P = 0.008). CONCLUSIONS: Postoperative adjuvant CT+ICRT treatment achieved equivalent 3-year DFS and OS but low complication rate compared to CCRT treatment in early stage cervical cancer patients with intermediate-risk.

Distribution pattern of lymph node metastases and its implication in individualized radiotherapeutic clinical target volume delineation of regional lymph nodes in patients with stage IA to IIA cervical cancer.

BACKGROUND: To study the distribution pattern of lymph node metastases of stage IA to IIA cervical cancer and to clarify the individualized clinical target volume delineation of regional lymph nodes (CTVn). METHODS: A total of 665 cases with International Federation Gynecology and Obstetrics stage IA to IIA cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy were retrospectively reviewed. The clinicopathological factors related to lymph node metastases were analyzed using logistic regression analysis. RESULTS: Pelvic lymph node metastases were found in 168 of 665 patients resulting in a metastasis rate of 25.3%. Binary logistic regression analysis showed that age, lymph vascular space involvement, and deep stromal invasion statistically influenced pelvic lymph node metastases (p = 0.017, < 0.001, < 0.001, respectively). Pathological morphology type, lymph node metastases of the obturator, the external iliac and internal iliac, and the para-aortic had a strong influence on lymph node metastases of the common iliac (p = 0.022, 0.003, < 0.001, 0.009, respectively). Tumor size and lymph node metastases of the common iliac were significantly related to lymph node metastases of the para-aortic (p = 0.045, < 0.001, respectively). Lymph node metastases of the obturator, the external iliac and internal iliac were strongly correlated to lymph node metastases of the circumflex iliac node distal to the external iliac node (CINDEIN; p = 0.027, 0.024, respectively). CONCLUSIONS: Factors related to lymph node metastases should be comprehensively considered to design and tailor CTVn for radiotherapy of cervical cancer. Selective regional irradiation including the correlated lymphatic drainage regions should be performed.

The Treatment of Pelvic Locoregional Recurrence of Cervical Cancer After Radical Surgery With Intensity-Modulated Radiation Therapy Compared With Conventional Radiotherapy: A Retrospective Study.

OBJECTIVE: The aim of this study was to investigate the therapeutic response and toxicity of intensity-modulated radiation therapy (IMRT) or conventional radiotherapy (c-RT) as adjuvant therapy in patients with pelvic locoregional recurrence of cervical cancer after radical surgery. METHODS: This retrospective study included 161 patients with unresectable pelvic locoregional recurrence of cervical cancer after radical surgery between March 2003 and May 2012. All patients were initially diagnosed with International Federation of Gynecology and Obstetrics stage IB-IIA cervical cancer and received radical hysterectomy and pelvic lymphadenectomy. A total of 82 patients were treated with c-RT, whereas the remaining 79 patients underwent IMRT. Intracavitary brachytherapy and concurrent chemotherapy were performed during external irradiation. RESULTS: The mean dose delivered to the planning target volume was significantly higher in the IMRT group than in the c-RT group (61.8 vs 50.3 Gy, P = 0.029). Intensity-modulated radiation therapy plans yielded better dose sparing of small bowel, bladder, and rectum than did c-RT (P < 0.05). Moreover, the IMRT patients experienced less acute and chronic toxicities (P < 0.05) and better short-term effects (complete response + partial response) than did those treated with c-RT (89.9% vs 63.4%, P = 0.03). Three- and 5-year overall survival rates were significantly higher in the IMRT group than in the c-RT group (3-year: 58.4% vs 39.1%, P = 0.012; 5-year: 35.4% vs 21.4%, P = 0.007). Furthermore, 5-year progression-free survival rates were significantly higher in the IMRT group than in the c-RT group (26.1% vs 15.1%, P = 0.031). CONCLUSIONS: Intensity-modulated radiation therapy achieved outcomes superior to c-RT in patients with pelvic locoregional recurrence of cervical cancer after radical surgery. The acute and chronic toxicities were acceptable, and the adjacent organs at risk were well protected.

[Incidence and influencing factors of distal external iliac lymph node metastasis in early cervical cancer].

OBJECTIVE: The distal external iliac lymph nodes are located along the external iliac artery between the deep circumflex iliac vein and the inguinal canal. Our study aimed to investigate the incidence of metastasis in distal external iliac lymph nodes and its association with clinicopathological factors in patients with early stage cervical cancer, and to determine the role of distal external iliac lymph nodes dissection in the surgery. METHODS: Five hundred and twenty-four patients with early stage cervical cancer underwent radical hysterectomy and bilateral pelvic lymphadenectomy in the Shandong Province Cancer Hospital between June 1995 and December 2011, and their clinicopathological features were analyzed retrospectively. RESULTS: Of the 524 patients, 124 (23.7%) had pelvic lymph node metastasis. The metastasis rates were 16.2% (85 of 524 patients) in the obturator lymph nodes, 12.2% (64 of 524 patients) in the internal and external iliac lymph nodes, 2.9% (15 of 524 patients) in the common iliac lymph nodes, 2.1% (11 of 524 patients) in the distal external iliac lymph nodes, and 1.7% (9 of 524 patients) in the para-aortic nodes. The incidence of isolated positive distal external iliac lymph nodes was 0.2%. Univariate analysis showed that lymphovascular space invasion, pelvic lymph node metastases (excluding distal external iliac lymph nodes) were significantly associated with distal external iliac lymph node metastasis (P < 0.05). Logistic regression analysis showed that pelvic lymph node metastasis (excluding distal external iliac lymph nodes) was the independent risk factor for metastasis to distal external iliac lymph nodes. CONCLUSIONS: In early stage cervical cancer, distal external iliac lymph node metastasis is rare, especially in cases with stage IA or without pelvic lymph node metastasis. Less extensive pelvic lymphadenectomy may be considered in these patients in order to reduce operative complications and improve patients' quality of life. The deep circumflex iliac vein may be an appropriate landmark for the caudal limit of external iliac lymphadenectomy. However, if pelvic lymph node metastasis (excluding distal external iliac lymph nodes) is found by intraoperative rapid pathological diagnosis, systematic pelvic lymphadenectomy including removal of the distal external iliac lymph nodes should be performed in order to reduce the risk of distant metastasis.

Distribution pattern of circumflex iliac node distal to the external iliac node metastasis in stage IA to IIA cervical carcinoma.

OBJECTIVES: This study aimed to investigate the metastatic rate of circumflex iliac node distal to the external iliac node (CINDEIN) and its associations with clinicopathological factors in patients with stage IA to IIA cervical cancer to determine whether dissection of CINDEIN had a role in surgery of these patients. METHODS: Six hundred thirty-three patients with the International Federation of Gynecology and Obstetrics stage IA to IIA cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy were retrospectively reviewed. The metastatic rate and distribution of the pelvic lymph nodes (PLNs) and CINDEINs were analyzed. RESULTS: The PLN metastatic rate was 25.6% (162 of 633 patients). Sixteen of 162 node-positive patients had CINDEIN metastases. Only 1 patient without PLN metastases had positive CINDEIN nodes. Univariate analysis revealed that other PLNs (including lymph nodes collected from obturator, external iliac, and internal iliac regions) and lymph vascular space involvement were the risk factors of CINDEIN metastases (P < 0.05). Other PLN metastasis (odds ratio, 50.6; 95% confidence interval, 6.6-386.7) was an independent risk factor for metastasis to CINDEIN by binary logistic regression analysis. CONCLUSIONS: Circumflex iliac node distal to the external iliac node metastases seemed to occur secondarily to widespread PLN metastases. In early stage cervical cancer, removal of the CINDEIN as a routine surgical procedure might be omitted to reduce operation time and minimize surgical morbidity.