Case Conference October 25th 2017

25-Oct-2017, Divisi Ginekologi Onkologi RSCM

Mrs. X

The chemotheraphy in Progressive cervical cancer IIIB post complete radiation

PPDS: Immanuel Santoso M (T3B, Oncology Rotation)

 

CASE DESCRIPTION

Mrs N, 34 years old, P2 complain vaginal bleeding since 7 month before admission, patient with history of post coital bleeding since 4 months before admission. The patient going to Budi Kemulian Hospital and perform cervical biopsy with the result squamous cell carcinoma differentiated moderately. On March 2017 patient get treatment at Banyumas Hospital and peform cervical biopsy for the second time with result Squamous cell carcinoma moderate differentiated (11/3/2017). Patient then get medication on PELNI hospital and referenced to RSCM. In RSCM, patient was diagnosed with Cervical Cancer IIIB and had complete radiation ( 25x Exteranal Radiation and 3x Brachiterapy).

Patient complain about mass at her left lower quadran since undergoing the second Brachiteraphy (27/7/17). The mass size 6x4cm, solid and immobile.

MRI examination and biopsy was performed to the mass with MRI result : The cystic solid mass in the left mesenterium extends to the left adnexa, and appears to be attached to the rectosigmoid causing bulging in the abdominal wall, suggestive of malignancy.

The biopsy result shown : positive spread of tumor, might be from cervix.

 

 

  

 

 

 

 

 

 

INTRODUCTION

 

Cervical cancer is the second most common malignancy in women with an estimated 493,000 new cases and 274,000 deaths in 2002. Although radical surgery and radiotherapy represent effective treatment modalities, up to one third of patients will develop progressive or recurrent tumours, the pelvis being the most common site of failure. The relapse rate of cervical cancer ranges between 11 and 22% in FIgo stages Ib-IIa and between 28 and 64% in FIGO stages IIb-IVa. cervical cancer recurrences can be central pelvic, lateral pelvic and extra-pelvic.

Central pelvic recurrence develops from the cervix and vagina after primary radiotherapy or from the vaginal cuff and central scar after radical hysterectomy. this relapse can be limited to the vaginal vault or can more often involve the bladder and/ or rectum. The treatment of choice for recurrent cervical cancer is a complicated clinical issue which must take into consideration the type of primary therapy, the site of recurrence (local, regional, and/ or distant), the disease-free interval, the patient symptoms, performance status, and the degree to which any given treatment might be beneficial.

Thus, combination treatments are emerging as the new standard of care in advanced cervical carcinoma. Despite the improved clinical outcomes, all treatments are ultimately palliative, and therefore, minimizing toxicity must remain a key objective. However, because a large number of patients with recurrent disease develop tumors in previously irradiated areas, malignant tumor cells are surrounded by fibrotic and avascular tissue. As a result, the concentration of chemotherapeutic agent in the tumor is not enough to achieve a high clinical outcome. Therefore, chemotherapy has been used only on patients with refractory cervical cancer or as an ordinary treatment option, as a palliative measure.

Patients who have previously been treated with RT and those who are not candidates for surgical resection should be offered chemotherapy. The approach to these patients is identical to the treatment of women with metastatic disease.

 

CLINICAL QUESTION

 

 

What question did the study ask?	PICO Analysis
Patients	Progressive Cervical cancer IIIB, complete radiation
Intervention	Cisplatin Chemotherapy
Comparison	Other Regimen chemoteraphy
Outcome	Respon rate, progression free survival, overall survival

 

 

 

 

 

METHODS

 

Search strategy

The search was conducted on ScienceDirect October 20 th, 2017, using the search tool containing the keywords “progressive cervical cancer IIIB AND complete radiation AND palliative” (Table 1). Search results were filtered by the engine according to the following criteria: articles published in English language with human population, last 10 years publsihed articles and using comparison study. Search strategy, result, and the inclusion and exclusion criteria are shown in the flowchart (Figure 1).

Table 1. Search strategy used in Pubmed and Science Direct conducted on October 20th, 2017

 

Engine	Search Terms	Results
Pubmed   Scholar google	progressive cervical cancer IIIB AND complete radiation AND palliative progressive cervical cancer IIIB AND complete radiation AND palliative	15   207

 

 

 

Figure 1. Flowchart of search strategy

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

SELECTION

The titles of the filtered results from Pubmed and Scholar google were screened using the inclusion criteria. A second screening was conducted by reading the abstract, and read for four full text articles and finally 1 article were included.

Discussion

 

Cervical cancer is the second most common malignancy in women with an estimated 493,000 new cases and 274,000 deaths. Although radical surgery and radiotherapy represent effective treatment modalities, up to one third of patients will develop progressive or recurrent tumours, the pelvis being the most common site of failure. The relapse rate of cervical cancer ranges between 11 and 22% in FIgo stages Ib-IIa and between 28 and 64% in FIGO stages IIb-IV.

Radiotherapy (RT) is a major treatment modality for cervical cancer and can achieve good treatment out- come in early-stage patients. However, substantial treatment failures still occur in the advanced-stage patients

The role of chemotherapy in this clinical setting is only palliative, and its administration is affected by several factors, such as decreased bone marrow function due to prior irradiation, limited drug distribution in previously irradiated tissues, and renal dysfunction due to ureteral obstruction

However, because a large number of patients with recurrent disease develop tumors in previously irradiated areas, malignant tumor cells are surrounded by fibrotic and avascular tissue. As a result, the concentration of chemotherapeutic agent in the tumor is not enough to achieve a high clinical outcome. Therefore, chemotherapy has been used only on patients with refractory cervical cancer or as an ordinary treatment option, as a palliative measure.

Chemotherapy is administered with palliative intent to patients with distant or loco-regional failures not amenable by surgery or irradiation. cisplatin-based combination chemotherapy increases response rates when compared with single-agent cisplatin, but median overall survival is usually shorter than one year. However some cases of unexpected long-term disease-free survival after salvage chemotherapy have been reported in the literature (139,140). In a GOG phase III trial the combination topotecan + cisplatin obtained a significantly longer progression-free survival and overall survival when compared with single-agent cisplatin in patients with metastatic or recurrent or persistent cervical cancer

At the present time, there is no effective treatment for metastatic disease and recurrences. Studies of cisplatin chemotherapy in cervical cancer demonstrate response rates of approximately 20%–30% with a median survival of 6–7 months. For recurrent or metastatic disease, chemotherapy is palliative. Complete responses are unusual and generally limited to patients with lung metastasis (Berek et al 2005). The high mortality rate, low response rate to available treatments and short survival mandates investigation into more effective therapies.  Chemotherapy represents the best therapy for recurrent disease not curable by exenterative surgery. Chemotherapy is also the most reasonable option for patients presenting with distant metastases

Cisplatin is the most widely used drug, with a response rate of 17-38% and a median overall survival of 6.1-7.1 months. A Gynecologic Oncology Group (GOG) randomised trial compared 50 mg/m2 of cisplatin vs. 100 mg/ m2 vs. 20 mg/m2, days 1-5 every 3 weeks in 497 patients. the response rates were 20.7, 31.4 and 25.0%, respectively, the median progression-free interval ranged from 3.7 to 4.6 months and the median overall survival ranged from 6.1 to 7.1 months. Cisplatin at 100 mg/m2 single dose achieved a higher response rate than cisplatin at a dose of 50 mg/m2 (p=0.015), without any improvement in the clinical outcome and with a greater haematological toxicity and nephrotoxicity. therefore, 50 mg/m2 is the recommended dose of cisplatin.

A GOG study randomly allocated 294 patients with stage IVb or recurrent or persistent cervical cancer to receive either cisplatin (50 mg/m2) or topotecan (0.75 mg/m2, days 1-3) + cisplatin (50 mg/m2, day 1, every 3 weeks). Combination chemotherapy obtained a higher response rate (27 vs. 13%; p=0.004), a longer median progression-free survival (4.6 vs. 2.9 months; p=0.014) and a longer median overall survival (9.4 vs. 6.5 months; p=0.017). This is the first randomised phase III trial demonstrating a survival advantage for combination chemotherapy vs. single-agent cisplatin.

Combination treatments are emerging as the new standard of care in advanced cervical carcinoma. Despite the improved clinical outcomes, all treatments are ultimately palliative, and therefore, minimizing toxicity must remain a key objective. In this respect, carboplatin may be a suitable substitute for cisplatin in combination regimens. The dose can be tailored to renal function and carboplatin has a more favorable non-hematologic toxicity profile. In ovarian cancer, carboplatin has been demonstrated to be equally efficacious to cisplatin, but better tolerated.

The new update on 2013, The Japan Clinical Oncology Group conducted a randomized Phase III study to evaluate the clinical benefit of TC (Carboplatin – Paclitaxel) compared with TP (Cisplatin-Paclitaxel) for patients with advanced or recurrent disease. The objective response was 60% for TP and 62% for TC. The median OS and PFS were 18.3 and 6.9 months for TP and 17.5 and 6.2 months for TC. Thus, TC proved comparable with TP in terms of its antitumor activity. The TC was also less toxic than TP in inducing febrile neutropenia, creatinine elevation, and nausea/vomiting. This Phase III study therefore drew the conclusion that TC could be recommended as the new standard treatment for advanced and recurrent cervical cancer.

 

Conclusion

 

For patient with Progressive cervical carcinoma post radiation, we suggest to perform chemotheraphy.

,