Logo MSM

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo MSM Logo MSM Logo MSM

07 September 2021: Clinical Research

Clinical Observation of Prophylactic Extended-Field Intensity-Modulated Radiation Therapy with Synchronous Chemotherapy in Locally Advanced Cervical Cancer

Xue Huang 1ABCDEFG , Mingming Fang 2BCF , Lin Zhu 1BCDF , Cheng Gu 2ABG , Han Cui 3BCDG , Chun Yang 4ACDF* , Yuxing Yang 1ABDF*

DOI: 10.12659/MSM.930457

Med Sci Monit 2021; 27:e930457

Abstract

BACKGROUND: We aimed to evaluate the value of prophylactic extended-field intensity-modulated radiation therapy (IMRT) in the treatment of locally advanced cervical cancer with multiple pelvic lymph node metastases (≥2) and negative common iliac and paraaortic lymph nodes.

MATERIAL AND METHODS: Thirty-four patient with newly diagnosed cervical cancer (IB1-IVA) and multiple pelvic lymph node metastases (≥2) confirmed by computed tomography and magnetic resonance imaging were randomly divided into an extended-field group (17 patients) and a pelvic-field group (17 patients). In the extended-field group, we added the drainage area of paraaortic lymph nodes on the pelvic field. The pelvic field was administered Dt 45.0 to 50.4 Gy, while the drainage area of paraaortic lymph nodes was administered Dt 40.0 to 45.0 Gy. Both groups were given Irl92 intracavitary radiotherapy after 3 weeks of external irradiation. The total dose of point A was 25.0 to 30.0 Gy, fractional 6.0 to 7.0 Gy. All patients had concurrent platinum-based chemotherapy once weekly until the end of radiotherapy.

RESULTS: No paraaortic lymph node metastasis was found in the extended-field group (P=0.0184), and disease-free survival (DFS) was prolonged (P=0.0286). Adverse effects in patients with III-IV degree myelosuppression were increased in the extended-field group (P=0.0324). However, all patients recovered after symptomatic treatment.

CONCLUSIONS: Prophylactic extended-field IMRT with chemotherapy reduced the metastasis rate of paraaortic lymph nodes and prolonged the DFS in patients with locally advanced cervical cancer and multiple pelvic lymph node metastases (≥2), while the toxic adverse effects were tolerated.

Keywords: chemoradiotherapy, Radiotherapy, Intensity-Modulated, Uterine Cervical Neoplasms

Background

Cervical cancer is a common malignant tumor in women. It ranks as the fourth most common malignant tumor in women in morbidity and mortality [1]. To date, radiotherapy, surgery, and chemotherapy are the major treatments for cervical cancer. For early-stage cervical cancer (IA–IIA), simple radical surgery or radical radiotherapy can be used with a good prognosis and a 5-year survival rate of more than 80% [2,3]. For middle-stage and locally advanced cervical cancer (IIB–IVA), concurrent chemo-radiotherapy is the main treatment, and the recurrence or uncontrolled rate fluctuates between 29% and 38% [4].

Paraaortic lymph node metastasis is a common treatment failure in advanced cervical cancer after chemo-radiotherapy [5,6], and the prognosis of patients with cervical cancer is significantly worse once periaortic lymph node metastasis occurs after chemo-radiotherapy [7]. At present, extended-field (pelvic+paraaortic) radiotherapy is required for patients with locally advanced cervical cancer and positive common iliac or paraaortic lymph nodes, while for those with negative common iliac or paraaortic lymph nodes, the standard treatment is still platinum-based chemotherapy, concurrent with pelvic radiotherapy [8,9]. However, for patients with high-risk factors for paraaortic lymph node metastasis, there is still no consistent conclusion on whether to perform prophylactic extended-field radiotherapy [10,11].

The aim of our study was to evaluate the efficacy and toxicity of prophylactic extended-field intensity-modulated radiation therapy (IMRT) with synchronous chemotherapy in the treatment of locally advanced cervical cancer with multiple pelvic lymph node metastases (≥2) and negative common iliac or paraaortic lymph nodes.

Material and Methods

INCLUSION CRITERIA: The inclusion criteria were as follows: (1) age ≤75 years old; (2) Karnofsky performance score (KPS) ≥70; (3) no serious physical disease; (4) no distant metastases, including lung, liver, and bone; (5) IB1–IVA cervical cancer with multiple pelvic lymph node metastasis (≥2) diagnosed by gynecological examination and pathology and confirmed by computed tomography (CT)/magnetic resonance imaging (MRI); and (6) patient had not undergone any other treatment. CT/MRI short diameter ≥1 cm or short diameter less than 1 cm but with a central low-density necrotic area was considered as the diagnostic criteria of pelvic lymph node metastasis in the present study [12]. The clinical staging was based on the 2009 Federation of Obstetrics and Gynecology (FIGO) clinical staging criteria [13].

CLINICAL INFORMATION: We collected 34 cases of newly diagnosed cervical cancer (IB1~IVA) with multiple pelvic lymph node metastases (≥2) confirmed by CT/MRI from December 2015 to November 2019 at the Changzhou Tumor Hospital. All selected patients voluntarily participated in the study and were randomly divided into 2 groups: an extended-field group (17 patients) and a pelvic-field group (17 patients). The patients were fully informed of the advantages and disadvantages of treatment and their respective adverse reactions. The groups were comparable in age, KPS, tumor size, pathological type, and clinical stage (P>0.05). The detailed clinical information of 34 patients is shown in Table 1. This research was approved by the Ethics Committee of the Changzhou Tumor Hospital Affiliated with Suzhou University.

TREATMENT: All patients received IMRT combined with intracavitary brachytherapy. Patients were instructed to drink 800 mL water after fully emptying their bladder 40 min before CT positioning. The patients were fixed with a body membrane in the supine position. The CT scan area was obtained from the 10th thoracic vertebra to 10 cm below the ischial tubercle (slice thickness: 5 mm). The images were transmitted to the planning system (Eclipse, Varian, USA) for further radiotherapy planning design. In the extended-field group, we added the drainage area of the paraaortic lymph nodes on the pelvic field. The clinical target volume (CTV) included the paraaortic lymph nodes, intra iliac, extra iliac, presacral, obturator, and common iliac lymphatic drainage areas as well as the uterus, appendages, cervix, and vagina. The upper bound was the left renal vein, and the lower bound was determined by the invasion of the vagina. The CTV of the drainage area of the paraaortic lymph nodes was as follows: The anterior bound was 5 mm in front of the inferior vena cava and abdominal aorta, the posterior bound was the vertebral anterior border, and the bilateral bound was in the medial of the psoas muscle. The CTV delineation of the pelvic region was based on the CTV delineation guidelines recommended for radical radiotherapy of cervical cancer [14]. The planned target volume (PTV) was 0.7 cm, extended on the basis of the CTV, and appropriate modifications were made to the anatomical barrier and adjacent organs at risk. At the same time, we contoured the rectum, bladder, spinal cord, small intestine, and kidney as risk organs. The treatment plan was evaluated and optimized according to the dose (such as cold spot, hot spot), conformal degree, and dose volume histogram.

A Varian Clinac IX linear accelerator (6MV X-ray, IMRT) was used in this study, with a PTV prescription dose of 1.8 to 2.0 Gy per fraction, 5 times per week, and 25 to 28 fractions. The total dose was Dt 40 to 45 Gy in the paraaortic lymphatic drainage area and 45.0 to 50.40 Gy in the pelvic cavity. Dose requirements were 95% of PTV volume accepted as ≥prescription dose; 93% of prescription dose was ≤1%, and 110% of prescription dose was ≤1%. The dose limit of organs at risk were as follows: The irradiated volume of the rectum received more than 50.0 Gy exposure volume (V50) ≤30%; bladder 50.0 Gy exposure volume (V50) ≤30%; small intestine 30.0 Gy exposure volume (V30) ≤40%; spinal cord maximum dose ≤45.0 Gy; and kidney 15.0 Gy exposure volume (V15) ≤50%. The superaddition dosage of parauterine or pelvic lymph nodes was made according to the gynecological and imaging examinations. The prescription dose was 6.0 to 8.0 Gy, 2.0 Gy/fraction, 3 to 4 times in total. After 3 weeks of external irradiation, Irl92 intracavitary radiotherapy was given. The dosage of a point A prescription was 25.0 to 30.0 Gy, 6.0 to 7.0 Gy/fraction, and a total of 4 to 5 fractions.

Platinum-based synchronous chemotherapy was performed once per week until the end of radiotherapy. Patient vital signs and adverse reactions were closely observed during the period of treatment, and chemotherapy was stopped if necessary.

SHORT-TERM EFFICACY EVALUATION: Gynecological examination and pelvic CT/MRI were performed 1 to 3 months after the end of chemo-radiotherapy. The short-term efficacy was evaluated by RECIST 1.1 as complete remission (CR), partial remission (PR), stable lesion (SD), or progression of disease (PD) [15].

EVALUATION OF RECURRENCE AND METASTASIS:

The patients were reexamined every 3 months in years 1 and 2, every 6 months in years 2 to 5, and yearly 5 years after the end of chemo-radiotherapy. The reexamination included gynecological examination, cervical/vaginal cytology, squamous cell carcinoma antigen (SCC Ag), thoracic CT, whole-abdomen CT/MRI, and bone emission-computed tomography. Local recurrence was defined as in-field recurrence, and distant metastasis was defined as out-field metastasis.

LONG-TERM EFFICACY EVALUATION:

Disease-free survival (DFS) and overall survival (OS) were observed. DFS was defined as the time from the beginning of treatment to no recurrence and metastasis in the last follow-up. OS was defined as the time from the beginning of treatment to death for any reason or the survival time at the last follow-up.

EVALUATION OF ADVERSE REACTIONS: Acute hematologic and nonhematologic toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 [16]. Late radiotherapy response was evaluated by the advanced radiation injury classification standard of the United States Cancer Radiotherapy Collaboration Group (RTOG) [17].

FOLLOW-UP:

The follow-up time was from the beginning of treatment to death or the time of the last follow-up. The median follow-up period was 27 months (4–51 months), and the follow-up rate was 100%.

STATISTICAL METHODS:

This study was a prospective randomized controlled clinical trial. Thirty-four cases of newly diagnosed cervical cancer (IB1~IVA) with multiple pelvic lymph node metastases (≥2) confirmed by CT/MRI were collected from December 2015 to November 2019 at the Changzhou Tumor Hospital. The primary endpoint was DFS. The secondary endpoints included 3-year OS and toxicity. Stata 14.0 statistical software was utilized for the statistical analyses. The short-term efficacy, metastasis, recurrence rate, and adverse reactions were analyzed by Fisher’s exact probability test. Data were presented as the percentage of total samples that were assigned in each group. DFS and OS curves were done using the Kaplan-Meier test, and significance was determined by the log-rank test. P<0.05 was considered statistically significant.

Results

SHORT-TERM EFFECTS:

The short-term efficacy evaluation of all of the 34 patients was evaluated as effective (response rate: CR+PR), without SD and PD. There were 14 patients with CR (82.35%) and 3 patients (17.65%) with PR in the extended-field group. There were 13 patients (76.47%) evaluated as CR and 4 patients (23.53%) as PR in the pelvic-field group. There was no significant difference in the short-term efficacy between the 2 groups (P=1.0000).

RECURRENCE AND METASTASIS: Among the 34 patients, 3 (17.65%) had pelvic recurrence in the extended-field group, and 2 (11.76%) had pelvic recurrence in the pelvic-field group. There were 2 patients (11.76%) with distant metastases in both the extended-field group and pelvic-field group, and there was no significant difference between the 2 groups. In the extended-field group, no patients had paraaortic lymph node metastasis, but 6 patients (35.29%) had paraaortic lymph node metastases in the pelvic-field group, and the difference was statistically significant (Fisher’s test, P=0.0184) (Table 2).

LONG-TERM EFFICACY EVALUATION: The DFS and OS rates of the 2 groups are shown in Figure 1. There was a significant difference in DFS between the 2 groups (χ2=4.79, P=0.0286). However, the 3-year survival rate was 86.15% in the extended-field group and 64.29% in the pelvic-field group. There was no significant difference in the 3-year OS rate between the 2 groups (χ2=0.10, P=0.7460).

ADVERSE REACTIONS: There were 10 patients (58.82%) with III–IV degree myelosuppression in the extended-field group and 3 patients (17.65%) in the pelvic-field group, and the difference was statistically significant (P=0.0324). However, there were no significant differences between the 2 groups in the occurrence of radiation enteritis and radiation cystitis (Table 3).

Discussion

Synchronous chemo-radiotherapy is the primary treatment of middle-stage and locally advanced cervical cancer. Paraaortic lymph node metastasis is a common cause of failure in advanced cervical cancer after chemo-radiotherapy. Moreover, the prognosis of patients with cervical cancer is significantly worse once periaortic lymph node metastasis occurs after chemo-radiotherapy. Currently, pelvic radiotherapy with synchronous chemotherapy is still the standard treatment for patients with locally advanced cervical cancer and negative common iliac and paraaortic lymph nodes. However, for patients with high-risk factors of paraaortic lymph node metastasis, whether to undergo prophylactic extended-field radiotherapy is still under debate. A previous study declared that pelvic lymph node metastasis is an independent risk factor for paraaortic lymph node metastasis [18]. Multivariate analysis showed that FIGO stage III–IVA, SCC Ag >40 μg/L, advanced parauterine invasion, and positive pelvic lymph nodes are independent risk factors for recurrence and metastasis of paraaortic lymph nodes after pelvic radiotherapy. This study focused on patients with multiple pelvic lymph node metastasis (≥2) and negative common iliac and paraaortic lymph nodes to evaluate the value of prophylactic paraaortic extended-field radiotherapy for locally advanced cervical cancer.

Several studies on extended-field radiation therapy with concurrent chemotherapy in locally advanced cervical cancer have been conducted. A retrospective study was performed in patients with locally advanced cervical cancer and negative paraaortic lymph nodes in which a total of 62 patients received extended-field radiotherapy with synchronous chemotherapy, 71 patients received pelvic-field radiotherapy and synchronous chemotherapy, 26 patients received extended-field radiotherapy, and 44 patients received pelvic-field radiotherapy. The results showed that prophylactic paraaortic radiotherapy did not improve OS in the synchronous chemo-radiotherapy group [19]. Lee et al reviewed 206 cases of FIGO IB2-IVA cervical cancer patients (negative paraaortic lymph nodes) who received extended-field or pelvic-field IMRT. Among them, 20 patients (18.2%) in the pelvic-field group and 12 patients (12.5%) in extended-field group did not receive synchronous chemotherapy, and the remaining patients did receive synchronous chemotherapy. The 5-year survival rates of recurrence-free survival and OS in the pelvic-field and extended-field groups were 97.9% vs 87.6% (P=0.03) and 87.8% vs 74.5% (P=0.04), respectively. The results showed that prophylactic paraaortic radiotherapy improved the outcome of locally advanced cervical cancer [20]. A study conducted by Wakatsuki M et al was a prospective single-arm multi-institutional trial in which 95 cases were locally advanced cervical cancer with pelvic lymph node metastasis and without paraaortic metastasis in East and Southeast Asian countries. The 2-year local control, progression-free survival, and OS rates for all patients were 96%, 78%, and 90%, respectively. Acute grade 3 leukopenia was observed in 20 patients (21%), and late grade 3 gastrointestinal toxicity was observed in 3%. The results showed that the delayed prophylactic paraaortic radiotherapy decreased the rate of distant metastases and improved PFS and OS rates, without increasing toxicity [21].

Our study showed that there was no significant difference in short-term efficacy, pelvic recurrence, and distant metastasis rate between the 2 groups. Results showed that there were no patients with paraaortic lymph node metastasis in the extended-field group and 6 patients with paraaortic lymph node metastasis in the pelvic-field group. The prophylactic extended-field IMRT with synchronous chemotherapy decreased the metastasis rate of paraaortic lymph nodes (P=0.0184), and DFS was significantly prolonged in the extended-field group (P=0.0286). However, there was no significant difference in OS between the 2 groups (P=0.7460). The present results are inconsistent with previous studies. A retrospective study conducted by Park et al showed the difference was due to a higher proportion of younger patients, positive pelvic lymph nodes, and larger tumor volume in the extended-field group, and the upper bound of each group’s target area varied [19]. A study conducted by Wakatsuki et al was a prospective single-arm multi-institutional trial in which only IIB and IIIB stages were selected. The population examined was from East and Southeast Asian countries, the traditional radiotherapy technique was used, and the study spanned a long period (2007–2016). In addition, the study allowed various treatment methods based on the treatment situation of each country, rather than strict protocols. The present study is more innovative than the aforementioned studies in the following ways. First, it was a prospective randomized controlled clinical trial. Second, the cases were in the IB-IVA stage, and the individuals studied were exclusively Han Chinese who were born in areas south of the Yangtze River in China. Third, it contains recent data, with cases collected from December 2015 to November 2019. Fourth, all patients were uniformly treated with prophylactic extended-field IMRT with synchronous chemotherapy. Another significant reason for the difference between the present study and others is the lower number of patients and shorter follow-up time.

Traditional extended-field radiotherapy is controlled front and back or 4-field radiotherapy, which always produces severe adverse effects, especially with synchronous chemotherapy. Small et al (RTOG0116) used the traditional radiotherapy technique in extended-field radiotherapy combined with synchronous chemotherapy of cisplatin and showed that the incidence of a III–IV degree acute radiotherapy reaction was 81% and the incidence rate of delayed radiotherapy reaction of degree III–IV was 40% [22]. Compared with conventional radiotherapy, extended-field IMRT can further improve the conformal degree between a high-dose distribution area and target area, deliver a more uniform dose distribution in the target area, and effectively limit the average dose and high-dose volume of organs at risk [23]. A retrospective study analyzed 55 patients with cervical cancer who received extended-field IMRT synchronous chemotherapy and 52 patients who received pelvic IMRT synchronous chemotherapy [24]. The incidence of III and IV degree acute adverse reactions was 34.5% and 19.2%, respectively. In a preventive extended-field IMRT synchronous chemotherapy trial, Kim et al found that the incidence of III–IV degree acute thrombocytopenia in the extended-field group was significantly higher than that in the pelvic-field group [25]. There was no difference in the incidence of III–IV degree gastrointestinal adverse reactions between the 2 groups. Yap et al reported that the incidence of advanced urogenital and gastrointestinal toxicity was 11% in the extended-field group and 8% in the pelvic-field group [26]. To reduce the toxicity of the treatment in the present study, we conducted IMRT. The III–IV degree myelosuppression (58.82%) in the extended-field group was higher than that in the pelvic-field group (17.65%) (P=0.0324). There was no significant difference between the extended-field and pelvic-field groups in the occurrence of radiation enteritis and radiation cystitis. We concluded that although the myelosuppression can be increased in extended-field IMRT, the adverse effects are tolerable.

Conclusions

This study shows that prophylactic extended-field IMRT with synchronous chemotherapy can reduce the metastasis rate of paraaortic lymph nodes and prolong DFS in patients who have locally advanced cervical cancer with multiple pelvic lymph node metastases (≥2) and negative common iliac or paraaortic lymph nodes. The adverse effects were tolerable. However, the sample size in the present study was rather small. To further define the role of prophylactic extended-field IMRT in cervical cancer with high-risk factors, a multicenter prospective study with a large sample size is required.

References

1. Torre LA, Bray F, Siegel RL: Global cancer statistics, 2012: Cancer J Clin, 2015; 65; 87-108

2. Pfaendler KS, Tewari KS: Changing paradigms in the systemic treatment of advanced cervical cancer: Am J Obstet Gynecol, 2016; 214(1); 22-30

3. Tewari KS, Still MW, Penson RT: Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240): Lancet, 2017; 390(10103); 1654-63

4. Yessaian A, Magistris A, Burger RA: Radical hysterectomy followed by tailored postoperative therapy in the treatment of stage IB2 cervical cancer: Feasibility and indications for adjuvant therapy: Gynecol Oncol, 2004; 94(1); 61-66

5. Eifel PJ, Winter K, Morris M: Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: An update of radiation therapy oncology group trim (RTOG) 90-0l: J Clin Oncol, 2004; 22(5); 872-80

6. Ribeiro I, Janssen H, De BM: Long term experience with 3D image guided brachytherapy and clinical outcome in cervical cancer patients: Radiother Oncol, 2016; 120(3); 447-54

7. Lin SY, Tsai CS, Chang YC: The role of pretreatment FDG-PET in treating cervical cancer patients with Enlarged pelvic lymph node(s) shown on MRI: A phase 3 randomized trial with long-term follow-up: Int J Radiat Oncol Biol Phys, 2015; 92(3); 577-85

8. Lin SY, Tsai CS, Chang YC: Clinical practice guidelines in oncology: Cervical Cancer, Version 1, 2018

9. Marth C, Landoni F, Mahner S: Cervical cancer: ESMO Clinical practice guidelines for diagnosis, treatment and follow-up: Ann Oncol, 2017; 28(Suppl 4); iv72-83

10. Yap ML, Cuartero J, Yan J: The role of elective para-aortic lymph node irradiation in patients with locally advanced cervical cancer: Clin Oncol (R Coll Radiol), 2014; 26(12); 797-803

11. Liang JA, Chen SW, Hung YC: Low-dose, prophylactic, extended-field, Intensity-modulated radiotherapy plus concurrent weekly cisplatin for patients with stage IB2-IIIB cervical cancer, positive pelvic lymph nodes, and negative para-aortic lymph nodes: Int J Gynecol Cancer, 2014; 24(5); 901-7

12. Yang WT, Lam WW, Yu MY: Comparison of dynamic helical CT and Dynamic MR imaging in the evaluation of pelvic lymph nodes in cervical carcinoma: Am J Roentgen, 2000; 175; 759-66

13. Pecorelli S: Revised FIGO staging for carcinoma of the vulva, cervix and endometrium: Int Gynaecol Obstet, 2009; 105; 103-4; [Erratum in Int J Gynaecol Obstet. 2010;108(2):176]

14. Lim K, Small W, Portelanee L: Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiotherapy for the definitive treatment of cervix cancer: Int J Radiat Oncol Biol Phys, 2011; 79; 348-55

15. Eisenhauer EA, Therasse P, Bogaerts J: New respond evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1): Eur J Cancer, 2009; 45; 228-47

16. Trotti A, Colevas AD, Setser A: CTCAE v3.0: Development of a comprehensive grading system for the adverse effects of cancer treatment: Semin Radiat Oncol, 2003; 13(3); 176-81

17. Cox JD, Stetz J, Pajak TF: Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC): Int J Radiat Oncol Biol Phys, 1995; 31(5); 1341-46

18. Huang EY, Wang CJ, Chen HC: Multivariate analysis of para-aortic lymph node recurrence after definitive radiotherapy for stage IB-IVA squamous cell carcinoma of uterine cervix: Int J Radiat Oncol Biol Phy, 2008; 72(3); 834-42

19. Park SG, Jin HK, Oh YK: Is Prophylactic irradiation to para-aortic lymph nodes in locally advanced cervical cancer necessary?: Cancer Res Treat, 2014; 46(4); 374-82

20. Lee J, Lin JB, Chang CL: Impact of para-aortic recurrence risk-guided intensity-modulated radiotherapy in locally advanced cervical cancer with positive pelvic lymph nodes: Gynecol Oncol, 2017; 148(2); 291-98

21. Wakatsuki M, Kato S, Ohno T: Multi-institutional observational study of prophylactic extended-field concurrent chemoradiation therapy using weekly cisplatin for patients with pelvic node-positive cervical cancer in East and Southeast Asia: Int J Radiat Oncol Biol Phys, 2019; 105(1); 183-89

22. Small W, Winter K, Levenback C: Extended-field irradiation and intracavitary brachytherapy combined with cisplatin chemotherapy for cervical cancer with positive para-aortic or high common iliac lymph nodes: Results of ARM 1 of RTOG 0116: Int J Radiat Oncol Biol Phys, 2007; 68; 1081-87

23. Hatano K, Narita Y, Araki H: 3D-CRT and intensity modulated radiation therapy (IMRT): Gan To Kagaku Ryoho, 2003; 30(13); 2050-55

24. Ouyang Y, Wang Y, Chen K: Clinical outcome of extended-field irradiation vs. pelvic irradiation using intensity-modulated radiotherapy for cervical cancer: Oncol Lett, 2017; 14(6); 7069-76

25. Kim JH, Kim JY, Yoon MS: Prophylactic irradiation of para-aortic lymph nodes for patients with locally advanced cervical cancers with and without high CA9 expression of KROG 07.01): A randomized, open-label, multicenter, phase 2 trial: Radiother Oncol, 2016; 120(3); 383-89

26. Kap ML, Cuartero J, Yan J: The role of elective para-aortic lymph node irradiation in patients with locally advanced cervical cancer: Clin Oncol (R Coll Radiol), 2014; 26(12); 797-803

Coronavirus/Covid 19

08 September 2021 : Clinical Research

Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...

Med Sci Monit In Press; DOI: 10.12659/MSM.932788  

16 July 2021 : Review article

Silent Hypoxemia in Patients with COVID-19 Pneumonia: A Review

Med Sci Monit In Press; DOI: 10.12659/MSM.930776  

09 July 2021 : Database Analysis

A Simple Clinical Prediction Tool for COVID-19 in Primary Care with Epidemiology: Temperature-Leukocytes-CT...

Med Sci Monit In Press; DOI: 10.12659/MSM.931467  

In Press

20 Sep 2021 : Clinical Research

Automated Boluses and Delayed-Start Timers Prolong Perineural Local Anesthetic Infusions and Analgesia Foll...

Med Sci Monit In Press; DOI: 10.12659/MSM.933190  

16 Sep 2021 : Clinical Research

A Retrospective Evaluation of Operative and Postoperative Outcomes in Patients with Spinal Metastases from ...

Med Sci Monit In Press; DOI: 10.12659/MSM.932995  

15 Sep 2021 : Clinical Research

Polish Medical Air Rescue Interventions Concerning Pregnant Women in Poland: A 10-year Retrospective Analysis

Med Sci Monit In Press; DOI: 10.12659/MSM.933029  

15 Sep 2021 : Clinical Research

A Prospective Single-Center Study of the Effects of Repetitive Transcranial Magnetic Stimulation at 2-Week ...

Med Sci Monit In Press; DOI: 10.12659/MSM.933017  

Most Viewed

20 Mar 2020 : Clinical Research

Social Capital and Sleep Quality in Individuals Who Self-Isolated for 14 Days During the Coronavirus Diseas...

DOI :10.12659/MSM.923921

Med Sci Monit 2020; 26:e923921

15 Apr 2020 : Clinical Research

Psychological Impact and Coping Strategies of Frontline Medical Staff in Hunan Between January and March 20...

DOI :10.12659/MSM.924171

Med Sci Monit 2020; 26:e924171

05 May 2020 : Review article

An Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development

DOI :10.12659/MSM.924700

Med Sci Monit 2020; 26:e924700

26 Apr 2020 : Clinical Research

Comparison of Prevalence and Associated Factors of Anxiety and Depression Among People Affected by versus P...

DOI :10.12659/MSM.924609

Med Sci Monit 2020; 26:e924609

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750