February 11 th 2016 Dear Mr. Nalini Ranjan Basu, Thank you for reaching out to Tata Memorial Centre for an expert opinion in regard to assessing your treatment options. Navya is pleased to offer this online consultation service for Tata Memorial Centre. We had converted your case reports submitted to us on February 4 th 2016 into a structured summary to be reviewed by a medical oncologist in the Uro-Oncology Disease Management Group at Tata Memorial Centre. The report from that consultation including the expert opinion of the medical oncologist, was submitted to you on February 10 th 2016. You have followed with additional question(s). Navya is pleased to interpret for you the expert opinion from the medical oncologist and provide additional information. For your convenience, we have reproduced your questions in italics and within quotes. 1. Is the cancer spread to bones? The given bone scan and the PSA reports (as mentioned in the structured summary), suggests metastatic prostate cancer which has spread to the bones. 2. Is the patient s overall/general condition deteriorating because of the presence of bone metastasis? The patient s overall/general condition appears to be deteriorating as he is unable to continue to fight the cancer. Many of the symptoms are related to spread of cancer to the brain, although the brain MRI report of October did not show spread to brain, however this situation changes rapidly. Also, electrolyte disturbances and kidney/renal problems can also cause many of these symptoms and problems in patients with metastatic prostate cancer. 3. What is the recommended treatment for a better quality of life? A medical oncologist in the Uro-Oncology Disease Management Group at Tata Memorial Centre had reviewed the structured summary (as mentioned in the already uploaded expert opinion report submitted on February 10 th 2016) and for the given general condition i.e. ECOG/performance status of three (as mentioned in the structured summary), recommended symptomatic treatment and supportive care (as mentioned in the uploaded expert opinion report) for a better quality of life. Please note that the expert recommendation is to focus on supportive care measures only as mentioned in the report and to not actively treat the cancer as the side effects of any Navya Inc does not diagnose, treat, give orders, or have the ultimate authority over the care of any individuals. Page 1
anti-cancer therapy are more than any expected benefit from fighting the cancer at this stage. Through this online consultation service, Navya and Tata Memorial Centre cannot provide direct responses on curability of a disease/prognosis or life span of a patient. 4. Are the bones really fragile, as cautioned by the treating oncologist? Caution should be taken if the patient is walking anywhere or being moved anywhere such that he does not fall, and he should be handled/rolled/moved/transferred gently as there is risk of bone fracture due to weakening of the bones from cancer.. 5. Are there any alternative therapies to improve the general condition? It is best at this stage to focus on the patient s comfort and quality of life and to only focus on alleviating his pain, symptoms of problems breathing, nausea etc. and to not focus on anti cancer treatments. Navya does not advise on alternative treatments. The local treating oncologist opinion to stop medical treatment for the patient's advanced cancer at this stage is the same as the experts from Tata Memorial Centre at this time. We hope that the information provided to you has adequately answered your questions and resolved your concerns. Please do not hesitate to write to us or call us with any questions. Sincerely, Gitika Srivastava Navya Inc does not diagnose, treat, give orders, or have the ultimate authority over the care of any individuals. Page 2
CASE SUMMARY Navya ID 1960 Expert Opinion ID 2979, Mr. Nalini Ranjan Basu Current Diagnosis: Metastatic Prostate Cancer Age: 77 Years Old Gender: Male Past Medical History: Hypothyroid [Since 2009] Past Medical History: Osteoarthritis Past Medical History: Cholecystectomy [March 2009] Past Medical History: Meniere's Disease Past Medical History: Third Nerve Palsy First Presentation: [2009] Prior Complaint(s): Frequent urination, inconsistent urine flow [March 2009] PSA: 23.4 [August 10th 2009] Diagnosis Made By: Trucut Biopsy- Prostate [August 24th 2009] Malignant Disease: Adenocarcinoma Cancer Grade: I Gleason's Score: 7 (3+4) Clinical TNM Stage: Stage III- T3bN0M0 PSA: 13.91 [September 11th 2009] Bone Scan: Normal [October 15th 2009] Navya Inc does not diagnose, treat, give orders, or have the ultimate authority over the care of any individuals. Page 3
Prior Hormone Therapy #1: Hormone Therapy Start Date End Date Neoadjuvant Bicalutamide(50)qd October 14th 2009 May 22nd 2010 MRI Abdomen/Pelvis: 2.8*2.2cm Rt prostate nodule, extending to periprostatic fat & Lt seminal vesicle-proximal part, prostatomegaly.[october 28th 2009] MRI Spine: Normal [November 4th 2009] Prior Hormone Therapy #2: Hormone Therapy Start Date End Date Neoadjuvant Gos- Gos(10.8)*q3m November 11th 2009 August 2012 Navya Inc does not diagnose, treat, give orders, or have the ultimate authority over the care of any individuals. Page 4
Prior Radiotherapy #1: Site of Radiation Type Of Radiation Dosage Fraction Start Date End Date Neoadjuvant Prostate + Seminal Vesicle + Common Iliac & Int. Iliac & Pre Sacral + Right Ext. Iliac & Obturator + Left Ext. Iliac & Obturator IMRT 70 + 63 + 50.40 + 50.40 + 50.40 35 January 19th 2010 March 10th 2010 PSA: 0.04 [March 11th 2010] Bone Scan: Normal [November 20th 2010] Note: Pt was on regular follow up Second Presentation: [2013] PSA: 2.34 [October 3rd 2013] Complaint(s): Hardness/swelling/pain in Rt testicles. No gross urinary complaints except urgency. [November 2013] PSA: 6.4 [November 04th 2013] US Scrotum: 3.09*2.37cm Rt testicular lesion [November 18th 2013] MRI Prostate: Rt epididymal SOL; no active disease in prostate; superior/inferior pubic rami increase uptake [November 18th 2013] Navya Inc does not diagnose, treat, give orders, or have the ultimate authority over the care of any individuals. Page 5
Bone Scan: Increased radiotracer uptake- Lt 8th anterior rib at costochondral junction; minimally increased uptake over B/L isichia-? Metastasis [November 21st 2013] CT Abdomen/Pelvis: Normal [November 25th 2013] CT Chest: Normal [November 25th 2013] Prior Surgery #1: Surgery Surgery Date Primary Bilateral Orchiectomy December 5th 2013 Note: Granulomatous inflammation compatible with Tuberculosis, right epididymis; Left sided epididymal cyst PSA: 2.40 [March 27th 2014] Bone Scan: Increased uptake- multiple foci in the skull; Lt 8th anterior rib; multiple dorsolumbar vertebrae- D2, D10, D11, L1; Rt ischiopubic ramus lesion- Metastasis [June 10th 2014] Met: Bone: Yes PSA: 5.09 [June 14th 2014] Clinical TNM Stage: Stage IV- any T any N M1 Note: Bicalutamide stopped Prior Chemotherapy #1: Chemotherapy Start Date End Date Palliative/Metastatic Zol- Zoledronic acid(4)qm-q3m July 21st 2014 July 3rd 2015 Navya Inc does not diagnose, treat, give orders, or have the ultimate authority over the care of any individuals. Page 6
PSA: 18 [August 2014] CT Chest: Lt upper lobe of the lung nodule, L1 vertebral lesion- metastases [September 18th 2014] Met: Lung:?Yes CT Abdomen/Pelvis: An ill-defined hypodensity in segment IV b of liver- fat deposit [September 18th 2014] Prior Hormone Therapy #3: Hormone Therapy Start Date End Date Palliative/Metastatic Abiraterone(250)/Pred(5)_qd September 29th 2014 August 7th 2015 MRI Prostate: Prostatomegaly with Rt lobe enlarged [November 20th 2014] PSA: 10 [February 13th 2014] Third Presentation: [2015] Complaint(s): Rt thigh & lower back pain, occasionally upper back pain, weakness, weight loss, nausea & vomiting, loss of appetite [2015] PSA: 25 [August 04th 2015] Note: Stopped Abiraterone acetate Navya Inc does not diagnose, treat, give orders, or have the ultimate authority over the care of any individuals. Page 7
Prior Hormone Therapy #4: Hormone Therapy Start Date End Date Palliative/Metastatic Fosfestrol(120)qd August 7th 2015 September 18th 2015 Chemo SE: Deep Vein Thrombosis (Lower Limb); developed gynecomastia within 2 weeks PSA: 21[September 11th 2015] Prior Chemotherapy #2: Chemotherapy Start Date End Date Response Palliative/Metastatic C- Cyclophosphamide(30) September 2015 November 27th 2015 Disease Progression Bone Scan: Rt supraorbital skull lesion with multiple smaller skull bones foci. Multiple, cervical & dorsolumbar spine foci. Multiple, B/L ribs, B/L scapulae foci. Rt femur proximal metaphyseal. Rt ischial tuberosity- Progressive disease [October 27th 2015] PSA: 56[October 16th 2015] MRI Brain: B/L subcortical leucoaraiosis seen in both frontal & parietal lobes. No obvious deposits seen [October 23rd 2015] MRI Orbit: Normal [October 23rd 2015] PSA: 161 [November 27th 2015] Note: Advised to stop PSA testing Navya Inc does not diagnose, treat, give orders, or have the ultimate authority over the care of any individuals. Page 8
Fourth Presentation: [2016] Current Complaint(s): Pain in Rt inner thigh, lower back, Lt arm, weakness, vomiting & aphasia for 1 day, inability to walk for 7 days, bone swelling below throat near start of ribcage, dyselectrolytemia [January 2016] Note: Disoriented, loss of speech, non responsive- hospitalized, given supportive care [January 1st 2016] Bone Marrow (Hematologic) Function: Adequate Kidney (Renal) Function: Adequate Liver (Hepatic) Function: Adequate Functional Status- ECOG Score: 3 General Condition: Patient is not able to care for self, needs assistance to clothe, needs assistance to bathe, general discomfort, requires assistance to walk, generalized weakness, vomiting mostly during evening, sleepless night, abdominal discomfort. Note: Patient/caregiver understands the risk factor of age, ECOG 3 and complexity of an online opinion based on above facts alone, yet desires the online opinion Navya Inc does not diagnose, treat, give orders, or have the ultimate authority over the care of any individuals. Page 9
Navya is a Cambridge, MA based company with offices in Bangalore, India. Navya is founded by graduates of Harvard University, MIT Sloan School of Management, and the Stanford School of Medicine. Navya s innovative and scalable decision making system is a technology powered solution for complex medical questions. Navya s software solutions are efficient engines to gather and synthesize individual goals of care, evidence specific to an individual medical case, and expert opinion, for evaluating treatment alternatives. Navya s goal is to assist in bringing clarity to the complexity of evaluating treatment alternatives. Navya s system collects the best available information and expertise from several worldwide sources relevant to a specific previously diagnosed medical case and assesses treatment decisions. For more information, please visit www.navyanetwork.com If you have any questions, please call +91 7022009550 or email gitika@navyatech.in Navya, Inc does not diagnose, prescribe medication, treat, or give orders, nor does Navya have the ultimate authority over the care of any individuals. Navya does not provide medical advice nor does its products, services, systems, projects, or programs constitute the practice of medicine, nursing, or any other health care profession. Any information provided by Navya as a result of use of Navya s products, services, systems, projects, or programs is being provided solely for educational and informational benefit and should not be considered diagnosis, treatment or a substitute for professional medical advice. Use of Navya s products, services, systems, projects, or programs does not establish a doctor-patient relationship. Navya encourages that individuals or patients using Navya s products, services, systems, projects, or programs share any reports or other information generated by the use of Navya s products, services, systems, projects, or programs with their treating health care provider. Use of Navya s products, services, systems, projects, or programs is voluntary and any information communicated as a result of the use of Navya s products, services, systems, projects, or programs is not intended to be, nor implied to be, and cannot and should not be used as a substitute for professional medical advice, diagnosis or treatment. Navya s products, services, systems, projects, or programs are limited to the provision of consultative services with respect to known or previously-identified condition and neither Navya, nor its employees, consultants or agents with whom it contracts will diagnose, treat, give orders, prescribe medications or have any authority over the care of any individuals. Navya s products, services, systems, projects, or programs will not involve any direct face-to-face encounters or physical examinations. Accordingly, individuals using Navya s products, services, systems, projects, or programs are encouraged to share and discuss any information provided as a result of use of Navya s products, services, systems, projects, or programs with their treating physician. The individuals or patients using Navya s products, services, systems, projects, or programs will be the ultimate decision maker over their own care. Navya Inc does not diagnose, treat, give orders, or have the ultimate authority over the care of any individuals. Page 10
INDIVIDUALS OR PATIENTS USING NAVYA S PRODUCTS, SERVICES, SYSTEMS, PROJECTS, OR PROGRAMS SHOULD NEVER DELAY OR AVOID SEEKING MEDICAL ADVICE OR ATTENTION FROM THEIR REGULAR HEALTH CARE PROVIDER OR TREATING PHYSICIAN OR DOCTOR BECAUSE OF SOMETHING THEY HAVE LEARNED THROUGH THEIR USE OF NAVYA S PRODUCTS, SERVICES, SYSTEMS, PROJECTS, OR PROGRAMS. SHOULD ANY UNEXPECTED MEDICAL EVENT OCCUR WHILE AN INDIVIDUAL OR A PATIENT IS PARTICIPATING IN THE USE OF NAVYA S PRODUCTS, SERVICES, SYSTEMS, PROJECTS, OR PROGRAMS, THE INDIVIDUAL OR THE PATIENT SHOULD IMMEDIATELY CALL THEIR HEALTH CARE PROVIDER OR TREATING PHYSICIAN OR DOCTOR OR LOCAL EMERGENCY ASSISTANCE NUMBER OR IMMEDIATELY VISIT THEIR LOCAL EMERGENCY ROOM. NAVYA AND ITS EMPLOYEES, CONSULTANTS, PARTNERS, AND EXPERTS ARE NOT AND SHALL NOT BE CONSTRUED AS BEING YOUR DOCTORS OR PHYSICIANS OR ONCOLOGISTS OR HEALTHCARE PROVIDERS FOR ANY PURPOSE WHATSOEVER. Navya Inc does not diagnose, treat, give orders, or have the ultimate authority over the care of any individuals. Page 11