Case Conference November 14th 2018

14-Nov-2018, Divisi Ginekologi Onkologi RSCM

Mrs. A, 40 yo, P2, 433-00-63

Cervical Cancer stage III B post EBRT(25 times) with bone metastasis


Objective Learning

Is it a place to manage cervical cancer stage III B post EBRT(25 times) with bone metastasis with chemotherapy?



Referral from Bangka Hospital with suspected advanced stage cervical cancer. Biopsy was carried out on September 6, 2018 in Bangka Tengah Hospital with the results of squamous cell carcinoma then referred to the RSCM. Patients complain of pain at the waist. A physical examination was performed and diagnosed with stage IIIB cervical cancer. Planned radiation.

Patient then performed external radiation 25 times. Afterwards, from the radiotherapy department, an pelvic MRI was examined for evaluation of external radiation. Found mass suspicious of metastasis in the sacrum bone. Heterogeneous solid mass accompanied by diffusion restriction on os sacrum as high as S3-S5 dominant right side size around 3.6x6.1x7.1 cm Advise on the radiotherapy section is not carried out by brachytherapy, suggesting fulldose chemotherapy.



General Status per November 12nd 2018

Awareness : Composmentis

BP : 128/89 mmHg. HR : 98 x/minute. RR : 20x/minute. T : 36.1oC

  weight: 76 kg  height: 160 BMI: 29.6

Head : Pale conjuctiva (-) Icteric Sclerae (-)

Lung : Vesicular breathing sound on both lungs, neither wheezing nor


Cardia : No murmur, no gallop

Abdomen : Supple

Extremity : Warm, no edema


Gynecology Examination

Inspection : external genitalia within normal limit

Speculum exam  : fibrosis cervix, fluor negatif, fluxus positif

RVT : fibrotic cervix,  no palpable mass at vaginal wall,  stiff right

                                           and left parametrium,  rectovaginal septum intact, smooth

                                           rectal mucosa without palpable mass




Laboratory Result on November, 5th 2018

CBC: 11.1/32.0/7.82/471000

Diff: 0.3/1.8/83.3/7.4/7.2

SGOT/SGPT: 26/48

Ur/Cr: 9.0/0.50

eGFR: 121.5

GDS: 469

Na/K/Cl : 128/2.8/82.9


Cystoscopy September 29, 2018:

Normal bladder


Rectoscopy October 22, 2018:

No visible mucosal infiltration, no obstruction.




Ultrasound at Klinik Anggrek September12nd, 2018


Normal uterine corpus. The uterine cavity does not contain an abnormal mass

Stratum regular, thin endometrial basal (<2 mm)

Cervix: contains an inhomogeneous solid mass with irregular shape and edge, measuring 46x24 mm, derived from malignancy masses. Mass of parametrial invasion (right)

Both ovaria shape and size are normal

There is no abnormal mass in both adnexa

There was no visible enlargement of bilateral paraaortic and parailiac lymph nodes

Others: Liver and both kidneys are normal. There are no ascites.

Conclusion: Cervical malignancy mass. The mass invasion of parametria.





Anatomical pathology report RSUD Bangka Tengah September 6th 2018:

Makroskopik: Beberapa potong jaringan terfragmentasi, volume +/- 1 cc, warna coklat kehitaman, raph

Mikroskopik: Sediaan berasal dari serviks, sebagian jaringan mengalami nekrosis luas, diantaranya dijumpai beberapa focus massa tumor membentuk struktur pulau sebagian tersebar satu, terdiri dari sel sel dengan inti bulat oval, pleomorfik, hiperkromatik sebagian vesikuler dengan anak inti prominent, sitoplasma eosinofilik. Tampak massa tumor telah menginvasi stroma jaringan ikat fibrokolagen bersebuk padat sel radang PMN, limfosit dan sel plasma

Kesan: Squamous cell carcinoma pada biopsy serviks

Note: Diferensiasi dan angioinvasi sulit ditentukan karena jaringan sebagian besar mengalami nekrosis luas.


Chest X-Ray on November, 8th 2018 ( RSCM )

Description :

No cardiomegaly, cardiothoracic ratio < 50%. No widening of aorta and mediastinum. Trachea in the midline, no thickening of both hilum. Normal vascular marking. No infiltrates/nodules at both lungs fields. Diaphragmatic curvature and costophrenic sinus are normal. The impression of visualized bones are good.

Conclusion :

- There is no abnormalities in heart and lungs.

- No visible metastatic nodules in both lungs.


MRI Pelvis without using contrast, October 30th, 2018


Hypointense T1W1 lesions, T2W1 hyperintense slight with restriction diffusion in the posterior uterine cervical region measuring about 1 x 0.9 x 0.7 cm and thickening of the anterior region of the cervix. No visible expansion of mass into parametrium or vagina.

It appears heterogeneous solid mass accompanied by diffusion restriction on os sacrum as high as S3-S5 dominant on the right side, the limit is relatively firm which infiltrates m. gluteus maximus and m. the right side of the gluteus medius is about 3.6x6.1x7.1 cm. No visible expansion of the mass to the right-left sacroiliac joint.

Multiple appearance of lymph nodes with restrictions on bilateral parailiac and inguinal diffusion with the largest short axis around 0.9 cm in the left inguinal.

Bladder forms an oval with thickened walls (thickness of about 4 mm). There is no mass / stone.

A mild dilatation of the visualized right-left distal ureter.

The rectosigmoid colon is good. No visible pathological dilatation or wall thickening.

Normal vascular structure of the minor pelvis. No visible pelvic or inguinal region lymphadenopathy.


- Diffusion-restricted lesions in the cervical region of the posterior uterus measuring about 1x9.9x0.7 cm with thickening of the anterior cervical region suspected of mass residue

- Bilateral parailiaca and inguinal lymphadenopathy with restricted diffusion with the largest short axis 0.9 cm

- Heterogeneous sacrum solid mass as high as S3-S5 dominant right side with infiltration to m. gluteus maximus and right-sided medius, suspected metastasis.

- Suspended cystitis ec post radiation with possible neurogenic bladder.


Bone Survey Results of the November 8, 2018

Technique: Radiographic bone survey in the bones of the cranium, thorax, lumbar, pelvis, bilateral humerus, and bilateral femur

Description: Appear geographic lytic lesions in S3-5 sacrum, especially the right side. Lesions with broad, expansive transition zones, partially indistinguishable, destroying the cortex, not clearly visible periosteal reactions.

Other bone structures appear intact, not apparent ostelitic / osteoblastic lesions, destruction or fracture. Spur formation appears in the anterior corpus L2-5, does not appear to narrow the joint gap.

Conclusions: Lytic lesions in S3-5 os sacrum, especially the right side, with malignant characteristics, suggestive of bone metastasis.

There is no picture of osteolytic / osteoblastic lesions, destruction or fractures of other bones that are optimally visualized. Lumbar spondylosis



November 7, 2018 Radiotherapy Results:

Performed external radiation using 2D techniques between October 2nd, 2018 until November 5th, 2018.

The number of doses received is 50 Gray, not given brachytherapy.

The current clinical response cannot be determined, with acute side effects still tolerable.

From the MRI evaluation, the mass around os sacrum was obtained, please consider giving fulldose chemotherapy.



Bone metastases from the carcinoma of the uterine cervix were observed in 0.8% to 23% of all cases. The rates of metastasis in each of the four clinical stages have been reported as follows: 4.0% in stage I, 6.6% in stage II, 8.0% in stage III, and 22.9% in stage IV. The most frequent site of metastasis was the vertebral column, particularly the lumbar spine (48%). For 67% of cases, lesions of the bone were detected within 1 year after completion of the initial treatment, and 75% of patients died within 1 year after detection of the metastasis. Patients younger than 45 with bone metastasis at the time of the cervical cancer diagnosis have a poorer prognosis than elderly patients. Bone metastasis can cause severe pain, pathological fracture, and disability. The diagnosis of bone metastasis is confirmed by a bone biopsy or positive results on more than two modalities including a bone scan, FDG-PET, X-ray, and MRI. Plain radiograph and bone CT are useful modalities for evaluating metastatic bone disease. MRI depicts the soft tissue extension to a better advantage. In addition, a bone scan is a useful diagnostic tool for the detection of distant metastases and to differentiate the isolated distant metastasis from diffuse metastasis. Patients with stage I and stage II carcinoma of the cervix may not require a bone scan. Currently, there is no specific widely accepted guideline for the treatment of patients with bone involvement. Patients who do not receive therapy for bone metastasis survive for less than 6 month.

Although the mechanism of bone metastasis is not clearly understood, primary tumor behavior, vascular supply, immune system, and bone environment can be associated. Once tumors metastasize to bone, neoplastic progress becomes incurable and patient survival is reduced. Moreover, bone metastases cause suffering because of severe pain, pathological fracture, and disability. Therefore, early diagnosis and proper treatment could lead to a better quality of life in patients with bone metastasis.


Problem to be discussed

Determine therapy for cervical cancer stage III B post incomplete radiation (EBRT 25 times) with bone metastasis.


Table1. PICO approach


Bone metastatic cervical cancer






Overall Survival




Search strategy

In order to answer the question above, we conduct a searching in PubMed site by using keywords, “Bone metastatic cervical cancer AND Chemotherapy AND Chemoradiation AND Overall Survival”. The search was conducted on PubMed on November  12th, 2018, there was 5 journals matched to the search terms.

Search strategy in PubMed conducted on


Search terms



“Bone metastatic cervical cancer AND Chemotherapy AND Chemoradiation AND Overall Survival





Figure 1. Flowchart of search strategy















From the articles, limitation were given for publication no abstract, not available in full text, not written in English, or articles which had no related titles. After the process, there were 5 articles found useful.


Critical Appraisal

1. Li H, Wu X, Cheng X, et all. Advances in diagnosis and treatment  of metastatic cervical cancer. Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. J Gynecol Oncol. 2016 Jul;27(4):e43.

2. Yoon A,  Choi CH, Kim HJ, et all. Contributing factors for bone metastasis in uterine cervical cancer. International Journal of Gynecological Cancer & Volume 23, Number 7, September 2013.

3. Makino H, Nishio S, et all. Treatment and prognosis of bone metastasis from cervical cancer (KCOG-G1202s). Departments of Obstetrics and Gynecology, Gifu University, Gifu. J. Obstet. Gynaecol. Res. 2016. doi:10.1111/jog.12956




A. Are the study results valid


1. Was there a representative and well-defined sample patients at a similar point in the course of disease?


2. Was follow-up sufficiently long and complete?


3. Were objective and unbiased outcome criteria used?


4. Was there adjustment for important prognostic factors?


B. What were the results?


1. How large is the likelihood of the otcome events in a specific period of time?


2. How precise are the estimates of likelihood? (consider 95% CI)

(p < 0.05)

C. Can the results be applied to your patients?


1. Were the study patients similar to my own?


2. Are the results useful for reassuring or counseling patients?


3. Is the treatment feasible in my setting?


D. Conclusions


1. The results or recommendation are valid?


2. The results clinically important?


3. The results are relevant to my practice?





Most patients with bone metastasis die within 1 year, treatment should aim not only at prolonging their lifespan but also improving the patient's quality of life and palliating their pain RT provided moderate palliation for treatable patients. However, although local RT was useful for pain relief, it did not affect the prognosis.1 RT provides good palliation for treatable patients, but the remission achieved is short lasting. Lesions of the bone treated by RT followed by cisplatin-based chemotherapy for patients with good general condition may be considered.

In one study, among 105 patients with bone metastasis, the median bone metastasis-free survival was 27 months. Most patients received a radiotherapeutic dose of 3,000 cGy (median, 3,000 cGy; range, 1,800 to 14,000 cGy) to bone metastasis, and approximately 60% of the patients showed improvements in pain. The median survival after bone metastasis was 10 months, and it was longer in the patients who received RT with or without chemotherapy

than in the patients who received chemotherapy alone as a salvage therapy (12 months vs. 7 months, p=0.01). When the treatment objective is pain relief, a single dose of 8 Gy treatment prescribed to the appropriate target volume is recommended as the standard dose-fractionation schedule for symptomatic and uncomplicated bone metastases. 1,2 However, a total dose of 30 Gy in 10 fractions is also considered as a standard method with lower rates of pathological fracture and spinal cord compression. With regard to chemotherapy, except for intravenous administration, palliative transcatheter arterial chemoembolization/embolization could be a suitable treatment method for symptomatic bone metastases because it is minimally invasive, repeatable, effective, and rapid-acting.1

The median overall survival (OS) of the 91 patients with bone metastasis was 53 months, and the median survival after bone metastasis was 10 months. The OS of the patients who had the histologic type SCC was longer compared with the patients with adenocarcinoma but statistically not significant (55 vs 34 months; P = 0.15), and the survival after bone metastasis. Between them was not statistically significant. Both OS and survival after bone metastasis, age, initial clinical stage, number and sites of bone metastasis, and coexisting metastatic lesion did not differ significantly. However, survival after bone metastasis was longer in the patients who received radiotherapy (T chemotherapy) than in the patients who received chemotherapy alone as a salvage therapy (12 vs 7 months; P = 0.01). The role of palliative radiotherapy for painful bone metastases is well established, and a total dose of 30 Gy in 10 fractions is considered a standard method.22,23 In our study, most patients received a radiotherapeutic dose of 3000 cGy and approximately 60% of the patients showed improvement of pain. The response rate of pain after palliative radiotherapy is reported at 58% to 73%. Our study showed that salvage radiotherapy improved survival after bone metastasis compared with chemotherapy, but the potential benefit of this remains questionable. Most patients who did not receive palliative radiotherapy had received previous high-dose radiation therapy to the area in which bone metastasis occurred, and there was concern for additional radiation-related injury. In addition, performance status of these patients should be considered.3

In general, the presence of bone metastasis is considered to predict poor outcome in cervical cancer. Yoon et al. reported that survival after bone metastasis was longer  in  the  patients  who  received  radiotherapy (with/without chemotherapy) than in the patients who received chemotherapy alone as a salvage therapy.

Patients younger than 45 with bone metastasis at the time of the cervical cancer diagnosis have a poorer prognosis than elderly patients. OS after the diagnosis of bone metastasis was significantly longer in patients without extra-osseous metastasis than in patients with extra-osseous.4




Once bone metastasis was recognized, the survival of these patients was poor and no factors were identified to predict survival of those patients.

This Patients who are relatively young(40 yo) have a poor prognosis but patients have good performance. However, MRI features show extra osseous bone metastasis to filtrate the right gluteus maximus and right gluteus medius. OS after the diagnosis of bone metastasis was significantly longer in patients without extra-osseous metastasis than in patients with extra-osseous.4

Recommendations for these patients are palliative symptoms.










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