#chemoradiotherapy

[dakotakazansky]

Ghost • Nineteen

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Warnings: 18+, Fluff, Angst, lots of Dumb Bitch Juice, Some Smut Pairings: Jake ‘Hangman’ Seresin x OC & Javy ‘Coyote’ Machado x OC Word Count: 3,239

Kota

I woke up the next morning feeling like I'd been hit by a Mack truck. I'm still wrapped up tightly in Jake's arms. I softly rub my cheek against his chest, trying to soothe myself back to sleep. If I'm sleeping, I can't feel the pain or numbness of the news I've received last night. No matter how hard I try to fall back to sleep, it's just not happening, my mind is racing and I just can't turn it off. Before I could truly register what was going on, my cheeks were once again stained with tears. 

I try to swipe the tears away quickly, not wanting to wake up Jake. I reach for my phone to check the time, 4:07 AM. I slowly crawl out of Jake's arms trying my hardest not to wake him, and make my way downstairs to the kitchen for a glass of water. I grab my glass of water, and stop over by the couch to grab my favorite throw blanket, the one Ice and I used to curl up under when we watched cartoons together before he had to leave for the base in the mornings. I pad my way through the house and down to his office. 

I knew Ice would be in bed with my mom, so I opened the door of his office, walked in and mostly closed the door back, leaving it open a crack. I swipe at the stray tears that threaten to spill over again. I take a sip of my water before placing it on the coaster I bought Ice one year for his birthday. It was one from a customized set, all Navy and Iceman themed. I wrap the throw around me and curl up in his huge office chair.

I try to come to terms with everything I was told yesterday but my mind is still racing. Stage 1 Cancer. I know mom loves and supports me, but I could lose my biggest supporter and fan ever. More tears well up and threaten to spill over as I look around the room at all of mine and Ice's accomplishments over the years. I close my eyes tightly trying to force back the tears, I'm already so exhausted from crying as is, and rest my head against the back of the chair. Sleep finally came back to me. 

A few hours later, I awoke to a huge soft palm placed on my shoulder, and I heard Ice call out, "She's okay, she's in here." Ice walks over to the door, and I hear him try to say quietly, "Would you mind just giving us a moment." I hear a deep sigh from Jake and a, "Yeah, I'll just be down in the living room with Sarah." Ice nods, shutting the door, and goes to sit on the couch, along the same wall the door is on. 

I get up from his chair, and walk over and sit next to Ice. I wrap my arms around his waist as he wraps his arms around me, holding me tightly to him. We sat in a comfortable silence for a bit, him waiting for me to speak first. When I don't speak up right away, he rests his head on the top of mine, hums softly, and rocks us back and forth gently. 

I eventually feel like I can speak, and I look up at him, biting at the inside of my cheek, fighting back tears again, finding the words I want to say first. Just barely about a whisper I croak out, "What kind of Cancer is it?" Ice continues to rock us, "It's laryngeal cancer. We found it early on, because I was having trouble swallowing, and was coughing more." He says giving me all the facts, knowing I'd have just asked for that next. 

I nod, "You said you start chemo and radiation next week?" He nods back to me, "They said I'm going to be getting Chemoradiotherapy, where they do my chemo and radiation together. They said having them together is the better and more efficient option."  

I nod again. "Ice, do you think you could call in a favor for me?" He looks down at me cocking his head to the side, giving me a questioning look, "I might be able to, what do you need?" I sigh, "I was wondering if you knew someone that could go to Jake's apartment in Lemoore, get my bike, and transport it down here. If you're going to be having treatment I want to be there with you when I can." I say sheepishly. 

"Of course I can arrange that Koty. We could have it here tomorrow after your Top Gun class." He says reassuringly. "But I don't want you to wear yourself down, coming to my treatments, and not doing your best in Top Gun Koty." I nod, knowing that was going to be said. 

He leans down to my ear and whispers, "You know, Jake's a good guy, he was really worried about you when he woke up and couldn't find you. Don't run from him, Koty. Make sure you lean on him for support too, and let him do the same if needed. Honestly you should go see him, so he stops worrying." I chuckle slightly, "I will, but could we just stay here for a few more minutes, please?" He nods, laying his head against the top of mine again, and goes back to humming softly, and letting me spend the time needed in his arms. I whisper just loud enough for him to hear, "Thanks dad, I love you."

Ice and I stayed with each other until I was good and ready to leave. I grabbed the blanket, wrapping it tightly around me like I was a little kid again, and opened the door to the office. As soon as that door popped open Jake was jumping up out of his seat near my mom and rushing to the door. 

As I walked out and Ice hung back in the doorway, I was engulfed in another set of strong arms. Jake kisses the top of my head, and whispers, "Darlin' I was so worried when I woke up and saw you weren't in bed with me. I checked the entire house and couldn't find you, I never thought to peek in your dad's office, you know for privacy reasons."

I wrap my blanketed arms around Jake's waist tightly and laid my head on his chest, "I'm so sorry, I never meant to worry you, you looked so peaceful sleeping, I just wanted some water and a few minutes to be alone, I didn't know I was going to fall asleep in there for hours." 

Jake kisses my temple now, rubbing small circles on my back with one hand, while his other hand rests softly on my head holding me to his chest, "Darlin', don't you ever be sorry about your needs. I promise I'll always listen and understand. Why don't we go sit on the couch with your parents and watch some cartoons, you know, for old times sake." 

I look up at Jake, eyes watering from this kind and thoughtful gesture, "Thank you, I'd really like that." I say shakily. He wraps an arm around me leading me to the couch, with my parents following us. I end up sandwiched between my two favorite men, while my mother sits on the other side of Ice. 

Mom ends up putting some cinnamon rolls into the oven, and we have a wonderful little family breakfast and watched all sorts of cartoons for nostalgia's sake. I couldn't have asked for a more kind and caring person out of Jake, what I thought was going to be just a family dinner turned out to be so much more, but in the end it turned out to be a family bonding moment with Jake involved too.

Around 11:30 AM, after a few hours of cartoons and having breakfast and bonding time with all my favorite people, Jake and I head upstairs to get cleaned up. I pack up my acoustic guitar and decide it's coming with us. We also snagged a few of my framed photos to put up around the house. Before we headed out, I gave dad Jake's garage code, and told him to text or call me when his first treatment appointment was scheduled. 

Once we were back in Jake's truck, I sat in the middle of his bench seat, and leaned against him for the hour ride home, while he had an arm wrapped around me. "Jake?" I say, my voice never louder than a whisper, clearly still extremely exhausted. "Hmm?" He hums back to me, while glancing at me quickly before looking back at the road. 

"I didn't want to impose anything on you or make you feel like a chauffeur," I paused for a moment to gain some more energy, "so I asked Ice to have one of his buddies go to your apartment in Lemoore and grab my bike for me. I didn't want to make you uncomfortable driving me to Ice's treatment appointments." He nods understanding, "Perfectly fine Darlin', if you do want me to support you and go with you one day, don't be afraid to ask." 

I nod to him, then turn to kiss his cheek softly, "Thank you Jake, you really don't know how much that means to me." He smiles saying, "Anytime Darlin', but when were you going to tell me about that?" He says point towards the guitar case. I chuckle a little, "I don't know, maybe I wanted to shock you with all my talents all at once." He just shakes his head laughing a little, "Darlin', what am I going to do with you?" I shrug softly against his side, "I dunno, love me anyways?" 

We finally get back home, and we unload the few things we brought back with us. It's still pretty early on in the day, but Jake offers, "Darlin', do you wanna go take a nap?" How this man knows me this well, I'll never understand. I nod before yawning one of those whole body, shaking your entire soul yawns. "C'mere Darlin'." He says before picking me up and carrying me to the bed. 

He holds me tightly, and places a kiss on my temple. "How about I plan a little outing for later this afternoon, after your nap?" I nod my head against his chest, not knowing that he's already got it planned. I mumble, voice deep with sleep, "I'd like that very much." Another huge yawn escaping my lips before succumbing to sleep once again. 

—

I wake up, feeling colder than usual. I pry my eyes open against the midday sun shining into the room. I look over to the alarm clock on the nightstand to see it's been a little over a half an hour since we'd laid down for the nap. I see one of Jake's zip up jackets nearby and shrug it on, before zipping it up about halfway. My arms are hidden in the sleeves of the jacket that is about two or three sizes too big for me. I pad my way out of the room, and towards our living room. "Cowboy?" I call out, trying to locate where he's gone. No reply, I walk over to the front windows to check outside for his truck, it's gone. 

I went to grab my phone, and as soon as I tapped the screen, I saw that Jake had not only put my phone into do not disturb mode, but had sent me a message saying that he's running to the store and will be back as soon as possible. I look at the timestamp of the message, it was sent about 15 minutes ago. 

I'm not sure how much longer it'll be until he gets back, so I go ahead and start a load of our laundry, before going to lay back down. I turn on one of my many playlists, pop my AirPods into my ears, and turn the music up a little louder than normal. I close my eyes and soak in the music. 

After a few songs I feel a dip in the bed and open my eyes to see Jake sitting next to me. I smile softly, sitting up in bed now, "Hey there Cowboy." Jake kisses my temple, "Hello there sweet girl. You want to start getting ready to head out?" I nod and throw on a very easy and comfortable outfit and Jake and I make our way out of the house again, towards the surprise outing he has planned for us.

Jake helps me into his truck, before getting in himself and starts off towards our location. About a 5-10 minute drive later and we are pulling up to the beach, just before sunset. He parks the truck and helps me out. He leans down and I chuckle at him, "What are you doing?" He just laughs before saying, "Hop on!" I hop up onto his back, and he walks to the back of the truck. He grabs out a picnic basket, a beautiful bouquet of red and white roses, with some baby's breath, and my guitar case. I gasp on his back, grabbing my guitar case and carefully sling the strap of it over my shoulder. 

He carries me on his back down to the beach where a blanket is already set up, and he lets me down, he sets the picnic basket down, and hands me the flowers. "Jake, this is so sweet!" I say a little misty eyed. "Anything for you Sweet Girl." He replies back. 

We ate the various goodies he packed into the picnic basket, my favorite part being he remembered my favorite cupcakes, chocolate with chocolate frosting and small chocolate chips, or what I call, Triple Chocolate Threat. "Jake, you really didn't need to do all of this." I start to say before he cuts me off, "I know I didn't need to, but after the last day or two, I knew you'd enjoy and appreciate it." 

I eventually got my guitar out and strummed on it for a little bit before asking, "Any song requests?" I look over to Jake waiting for his answer. He thinks on it for a minute, "Do you know Burnin' It Down?" I thought for a moment, "By Jason Aldean?" He nods to me, "Yeah I do!" I begin to play the song, and sing it to Jake. He eventually chimes in with me about halfway until the end of the song.

 "Holy shit Kota, you're incredible, how did I not know this?" He says as I giggle, "Well cowboy, we've always got the radio up really loud in the truck while we sing along." He laughs, "Okay you got me there!" He requests a few more songs that we sing together before I pack up the guitar. 

Jake moves to where he's sitting between my legs, laying back against me. I run my fingers through his hair for a little bit before laying my head against the top of his. "Jake, can I ask you something?" He nods gently, "Of course Kota." 

"When did you know you liked me?" I ask shyly. "Well, there was multiple times darlin'." He pauses for just a moment, "I liked you as a person, the first day I met you in our plebe summer, you were so careful and kind to help me find our classrooms. I liked you as a friend, when you told off that one kid who tried to only befriend you for your dad the first week of classes. I liked you more than a friend when we started spending every day together, or when you flirted back with me that one night at the bar when I was dared to flirt with you. I liked you as a pilot, when you proved your worth to those shit heads who doubted you. But I think I liked you the most when you're just being unapologetically you." 

I'm so thankful he's in front of me, and can't see the massive amount of blush that has fully crept up all over my cheeks. He softly rubs circles on my leg, "When did you start to like me darlin'?" I think back for a moment, "Honestly this is going to sound so terrible, but I don't think I ever had a time where I fully realized I liked you until the parent trap date. Like I've always liked you, since like school but I think I denied myself the feelings not wanting to ruin our friendship that I never paid attention to the actual day or what happened." I sigh a little upset with myself. "Nothing to be upset about, sweet girl." Jake reassures me. 

We talked a little while longer, about our intentions and feelings for each other, as the sun went down beneath the horizon. We packed up our little beach picnic and took it all back to the truck. "Hey can we just go walk along the beach for a little bit?" I suggested not ready to leave just yet. Jake nods to me, taking my hand in his intertwining our fingers together. As we walked along the beach I started humming a song I'd heard that resonated with how I'm feeling currently with all the news I've gotten recently. "Whatcha humming there Darlin?" Jake asks, his eyebrow cocked up, as curious as ever. "A song that resonated with me recently. Wanna hear?" He nods to me.

I pulled my phone out of my pocket, skimmed through my playlist until I found the song. I turned the volume up on my phone before pressing play. The song starts and I sing along with it, 

—

Lately, I've been Scaring myself Going through changes But I need to let you know

Maybe I'm in The dark, no lighthouse I know I kept you waiting But I can't do this alone

—

Before I knew what was happening next, Jake had pulled me in and began slow dancing with me to the song, and encouraged me to keep singing along. 

—

Yeah, it's a long way back but I'm falling I been tryna cure my head, full of toxins I don't wanna drag you down where I'm failing But I don't wanna lose you now, so I'm saying

I would lay my guard down for you I would lay my guard down for you I would lay my guard down for you I would lay, I would lay, I would lay it down for you

—

Jake and I continued to dance along to the song until it finally came to an end. He pressed his forehead to mine, "Thank you sweet girl." I gave him a confused look, "What for?" He pulls me tightly to him, "For sharing this song with me, I know when things get rough you shut down, you try to push people away, your dad told me. Thank you for opening up to me." I nod and whisper, "You're welcome, and thank you, for being here even when you don't have, most people would've ran by now." 

He smiles at me, "Well I'm glad I'm not most people, Dakota Kazansky you mean the world to me." He pauses, getting nervous, "Dakota, would you, uhm, want to be my girlfriend? I don't want to spend another day without you as my girl." I nod, getting misty eyed again, "I would love to."

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[drcare4u]

Keytruda Plus Chemoradiotherapy May Represent New Standard of Care in Cervical Cancer Subset

A new study shows that Keytruda combined with chemoradiotherapy can significantly improve survival for patients with advanced cervical cancer. Keytruda (pembrolizumab) plus chemoradiotherapy, followed by Keytruda monotherapy, significantly improved survival versus chemoradiotherapy alone in newly diagnosed, previously untreated, high-risk locally advanced cervical cancer, according to updated…

[pacehospitalshyd]

Oral Cancer – Symptoms, Causes, Stages, Risk Factors & Complications  

Oral carcinogenesis, like other cancers, progresses from dysplasia to invasive phenotypes. Genetic and proteomic approaches have revealed molecular pathology. Contributions by congenital abnormalities in oncogenes, tumour suppressor genes, genomic instability, and epigenetic modifications could cause oral oncogenesis. Various risk factors could play a key role in enhancing the aforementioned genetic abnormalities.

Oral cancer symptoms :

A few of the common Oral cancer symptoms include fatigue, nausea, and pain. In other patients, the symptoms are not presented. Dentists often identify oral cancer during regular exams. The most common symptoms are:

Lump on the lips, mouth, throat or neck, or a feeling of cheek thickening

Red or white patches/spots on the gums, tongue, tonsil, or lining of the mouth

Persistent sore throat or feeling of something caught up in the throat

Difficulty in chewing, swallowing, or moving the jaws or tongue

Numbness of the mouth or tongue

Loosening of teeth or toothache

Hoarseness or change in voice

Pain or bleeding in the mouth

Dentures that no longer fit

Unexplained weight loss

Anorexia at later stages

Ear and/or jaw pain

Chronic bad breath

Changes in speech

Fatigue

Early signs of Oral cancer

Tongue cancer: The most common Early signs of Oral cancer is a painful sore on the tongue that increases gradually and doesn't heal, and bleeds easily.

Tonsil cancer: The earliest symptom of tonsil cancer is an enlarged tonsil, but if both tonsils are swollen or enlarged, it not is tonsil cancer.

Gums cancer and cancer at the floor of the mouth: Ulceration was the most frequent clinical appearance, followed by lesions, induration (thickening and hardening of soft tissues) and rupture.

Risk factors of oral cancer

Various risk factors of oral cancer can increase the potentiality of oral cancer, such as:

Chemical Factors

Biological Factors

Dental Hygiene and Related Factors

Nutritional Factors

Demographic factors

Complications of oral cancer

There could be several oral cancer complications, including medical phenomena such as dysphagia (difficulty swallowing) and aphasia (speech problems). Since oral cancer occurs in the orofacial part, patients may also suffer from self-esteem, social anxiety disorder, and reclusive ness (withdrawal from social life), considering an unaesthetic facial consequence.

A Taiwanese study from 2021 demonstrated an increased inclination towards the development of depression is seen in oral cancer patients. It is especially pronounced in patients suffering from tongue cancer, as they experience worse functional dysphagia when compared with patients suffering from oral cancer in other locations.

While oral surgery can significantly affect the treatment of cancer, it often causes significant function loss. Any side effects of chemoradiotherapy, such as mucositis, pharyngitis-related dysphagia, nausea, vomiting, and masticatory disorders, could further plunge the patient into their mental dungeon through social isolation. The result is even more pronounced when combined with painkillers, especially narcotic analgesics, as they are reported to possess a higher risk of depression.

As emotional instability is seen in all kinds of oral patients, the comprehensive treatment plan must subsume psychological counselling for both the patients and their family members, as the latter also experience emotional distress. The steady job of caregiving can negatively impact the connotations of psychosocial aspects.

Till date, the psychosocial interventions combined with the regular treatment of oral cancer demonstrated an overall positive effect on the patients. Although being a caregiver is challenging enough, additional unique psychological training can greatly amplify the patient's care and reduce the caregivers' mental burden.

*In addition to the information above, PACE Hospitals may also want to include information about their own oral cancer treatment program.

*They may want to highlight the experience and qualifications of their oral cancer specialists.

They may also want to provide information about the support services that are available to oral cancer patients at PACE Hospitals.

[healthcaretechnologynews]

GRG Health Competitive Intelligence (CI) Perspectives and Opinions, October 2022

The development:

In October 2022, Dostarlimab met its primary endpoint of Objective Response Rate (ORR) in a head-to-head trial against Pembrolizumab (KEYTRUDA, Merck) in NSCLC (vide PERLA trial – a global, randomized, double-blind phase II trial of 243 patients).

Write to us at enquire@grgonline.com Learn how GRG Health is helping clients gather more in-depth market-level information on such topics.

Opening thoughts:

Dostarlimab – an asset that GlaxoSmithKline (GSK) obtained by acquiring Tesaro, is proving dependable in sundry trials.

This is probably a blessing since the GSK – Tesaro transaction has had more than its fair share of headlines….and the price tag (USD5.1 billion) was not even at the top of that list!

However, a lot more must be done by GSK to ensure smooth sailing.

Thankfully, Dostarlimab -gxly injection (TSR-042, brand name JEMPERLI) is a key asset that has always remained in the spotlight, mostly for the right reasons.

Asset Outline: 

Profile – Dostarlimab-gxly injection (TSR-042, brand name JEMPERLI) is a humanized monoclonal antibody (IgG4 isotype) PD-1 inhibitor that targets the mismatch repair deficiency mutation (dMMR). Dostarlimab is particularly interesting since the dMMR mutation occurs in multiple indications (including breast, endometrial, uterine, prostate, rectal). Besides, dMMR tumors may also develop Microsatellite Instability (or MSI)

Potential – Dostarlimab’s potential is believed to be high; the asset was a healthy influencer (besides the oral PARP inhibitor Niraparib (brand name Zejula) and the TIM-3 mAb Cobolimab) that drove GSK to acquire Tesaro.

Performance – Since 2021, Dostarlimab is approved across the EU and the United States for recurrent or primary advanced dMMR endometrial cancer that has progressed on or following prior therapy with a Platinum-containing regimen. The initial approval was granted based on preliminary results vide GARNET trial or NCT02715284 since indication – specific therapies were unavailable for patients.

Asset Spotlight:

Past achievement – Dostarlimab was in further trials when it took centerstage (worldwide) in July/August 2022

o Claim to fame – Dostarlimab took centerstage because of its celebrated, outstanding results (100% remission of disease) in a subgroup of patients who had dMMR rectal cancer (all either Stage II or III disease)

o Claim specs – The study conducted at Memorial Sloan Kettering Cancer Center (MSKCC), New York (United States), intravenously dosed these patients with Dostarlimab every three weeks for a duration of six months

Relevance – Since the current SOC for rectal cancer is neoadjuvant Chemoradiotherapy (CRT) followed by Surgery and adjuvant chemotherapy, the celebration for Dostarlimab’s performance is understandable.

Recent achievement – In October 2022, Dostarlimab announced a landmark in NSCLC.

o Claim to fame – Dostarlimab met its primary endpoint (ORR) in NSCLC (vide Open label, Double blind PERLA trial)

o Claim specs – The study put Dostralimab head-to-head against Pembrolizumab (KEYTRUDA, Merck)

Relevance – Since Dostarlimab went head-to-head against KEYTRUDA which is widely regarded as a top intervention, evaluating Dostarlimab’s performance in detail is likely to establish its standing as one more promising option and/or a challenger.

Next steps – Hopefully, future data will show not just ORR but survival benefit too. This would help to clarify the extent of Dostarlimab’s advantage in a key indication vis-à-vis an established gamechanger (KEYTRUDA).

This is going to be relevant since ORR alone might not be accurately reflecting survival advantage.

The CI angle:

What generates interest –

o PERLA: GSK already has Zejula (which competes with the better – established LYNPARAZA, Astra Zeneca) in pharmacies. Now, with Dostarlimab meeting its primary endpoint in PERLA and progressing further in the COSTAR Lung trial - comprising patients with advanced NSCLC who progressed in spite of prior anti-PD-L1 therapy and chemotherapy, GSK’s future as an oncology player looks promising, currently.

What generates anxiety –

o dMMR Rectal cancer:

Trial span: The widely lauded rectal cancer study was constrained by the (low) number of patients and a single trial institution.

Durability of response: Evidence of durable response can emerge after these patients are followed for at least three years to assess (the absence of) recurrence.

Price point (and affordability): Given the trial results (and the cost of Tesaro’s acquisition), Dostarlimab is likely to be available at a steep price

Ø Reportedly, the nine doses of Dostarlimab that are required over a six-month period cost USD99,000 (INR 77 lakh). Such a price tag will adversely affect uptake, especially in the third world where future disease burden is likely to surpass the first world

Ø Further, third world markets are likely to be characterized by late diagnosis (poor prognosis), low per capita income, and poor penetration of insurance

o NSCLC:

The PERLA study included first-line patients (N = 243) with metastatic nonsquamous NSCLC and no known sensitizing EGFR, ALK or receptor tyrosine kinase-1 mutation, BRAF V600E mutation, or other genomic mutation for which an approved targeted therapy is available. How this affects Dostarlimab’s promise remains to be seen especially since the phase 2 PERLA study is not likely to enable any drug applications. Further, development plans for Dostarlimab in frontline NSCLC remain unclear

o Self-sufficiency:

Tesaro reportedly developed Zejula by licensing Astra Zeneca’s technology platform! This is not unusual in the industry but how it will affect Dostarlimab, GSK’s oncology outlook, and GSK’s tech-specific self-sufficiency remains to be seen

Closing Opinion:

The Tesaro portfolio is proving useful for GSK, representing promise in the medium term. However, all assets report a subset-specific disease focus besides lacking synergies with established interventions.

GRG Health’s CI engagements have also revealed that there is a lack of adequate awareness and engagement even for proven assets like ZEJULA. This is concerning.

Further, GSK seems to lack a coherent strategy ever since the loss of its Respiratory assets – it would be worrying if an erstwhile, established leader in respiratory diseases relies more on M&A than either organic evolution or balanced development for the way forward.

The collective effect of such concerns is probably reflected in the consistently low share price of GSK.

In view of the above and the potential crowding of the PD-1/L1 space, GSK should aggressively focus on generating robust, broad-based data across indications to firmly establish its portfolio in oncology at the earliest.

Visit our website now: https://www.grgonline.com/

[healthcaretoday1]

GRG Health Competitive Intelligence (CI) Perspectives and Opinions, October 2022

The development:

In October 2022, Dostarlimab met its primary endpoint of Objective Response Rate (ORR) in a head-to-head trial against Pembrolizumab (KEYTRUDA, Merck) in NSCLC (vide PERLA trial – a global, randomized, double-blind phase II trial of 243 patients).

Read more: https://www.grgonline.com/post/grg-health-competitive-intelligence-ci-perspectives-and-opinions-october-2022

Opening thoughts:

Dostarlimab – an asset that GlaxoSmithKline (GSK) obtained by acquiring Tesaro, is proving dependable in sundry trials.

This is probably a blessing since the GSK – Tesaro transaction has had more than its fair share of headlines…..and the price tag (USD5.1 billion) was not even at the top of that list!

However, a lot more must be done by GSK to ensure smooth sailing.

Thankfully, Dostarlimab -gxly injection (TSR-042, brand name JEMPERLI) is a key asset that has always remained in the spotlight, mostly for the right reasons.

Asset Outline:

Profile – Dostarlimab-gxly injection (TSR-042, brand name JEMPERLI) is a humanized monoclonal antibody (IgG4 isotype) PD-1 inhibitor that targets the mismatch repair deficiency mutation (dMMR). Dostarlimab is particularly interesting since the dMMR mutation occurs in multiple indications (including breast, endometrial, uterine, prostate, rectal). Besides, dMMR tumors may also develop Microsatellite Instability (or MSI)

Potential – Dostarlimab’s potential is believed to be high; the asset was a healthy influencer (besides the oral PARP inhibitor Niraparib (brand name Zejula) and the TIM-3 mAb Cobolimab) that drove GSK to acquire Tesaro

Performance – Since 2021, Dostarlimab is approved across the EU and the United States for recurrent or primary advanced dMMR endometrial cancer that has progressed on or following prior therapy with a Platinum-containing regimen. The initial approval was granted based on preliminary results vide GARNET trial or NCT02715284 since indication – specific therapies were unavailable for patients

Asset Spotlight:

Past achievement – Dostarlimab was in further trials when it took centerstage (worldwide) in July/August 2022

o Claim to fame – Dostarlimab took centerstage because of its celebrated, outstanding results (100% remission of disease) in a subgroup of patients who had dMMR rectal cancer (all either Stage II or III disease)

o Claim specs – The study conducted at Memorial Sloan Kettering Cancer Center (MSKCC), New York (United States), intravenously dosed these patients with Dostarlimab every three weeks for a duration of six months

Relevance – Since the current SOC for rectal cancer is neoadjuvant Chemoradiotherapy (CRT) followed by Surgery and adjuvant chemotherapy, the celebration for Dostarlimab’s performance is understandable

Recent achievement – In October 2022, Dostarlimab announced a landmark in NSCLC

o Claim to fame – Dostarlimab met its primary endpoint (ORR) in NSCLC (vide Open label, Double blind PERLA trial)

o Claim specs – The study put Dostralimab head-to-head against Pembrolizumab (KEYTRUDA, Merck)

Relevance – Since Dostarlimab went head-to-head against KEYTRUDA which is widely regarded as a top intervention, evaluating Dostarlimab’s performance in detail is likely to establish its standing as one more promising option and/or a challenger.

Next steps – Hopefully, future data will show not just ORR but survival benefit too. This would help to clarify the extent of Dostarlimab’s advantage in a key indication vis-à-vis an established gamechanger (KEYTRUDA).

This is going to be relevant since ORR alone might not be accurately reflecting survival advantage.

The CI angle:

What generates interest –

o PERLA: GSK already has Zejula (which competes with the better – established LYNPARAZA, Astra Zeneca) in pharmacies. Now, with Dostarlimab meeting its primary endpoint in PERLA and progressing further in the COSTAR Lung trial - comprising patients with advanced NSCLC who progressed in spite of prior anti-PD-L1 therapy and chemotherapy, GSK’s future as an oncology player looks promising, currently

What generates anxiety –

dMMR Rectal cancer:

Trial span: The widely lauded rectal cancer study was constrained by the (low) number of patients and a single trial institution

Durability of response: Evidence of durable response can emerge after these patients are followed for at least three years to assess (the absence of) recurrence

Price point (and affordability): Given the trial results (and the cost of Tesaro’s acquisition), Dostarlimab is likely to be available at a steep price

Ø Reportedly, the nine doses of Dostarlimab that are required over a six-month period cost USD99,000 (INR 77 lakh). Such a price tag will adversely affect uptake, especially in the third world where future disease burden is likely to surpass the first world

Ø Further, third world markets are likely to be characterized by late diagnosis (poor prognosis), low per capita income, and poor penetration of insurance

NSCLC:

The PERLA study included first-line patients (N = 243) with metastatic nonsquamous NSCLC and no known sensitizing EGFR, ALK or receptor tyrosine kinase-1 mutation, BRAF V600E mutation, or other genomic mutation for which an approved targeted therapy is available. How this affects Dostarlimab’s promise remains to be seen especially since the phase 2 PERLA study is not likely to enable any drug applications. Further, development plans for Dostarlimab in frontline NSCLC remain unclear

Self-sufficiency:

Tesaro reportedly developed Zejula by licensing Astra Zeneca’s technology platform! This is not unusual in the industry but how it will affect Dostarlimab, GSK’s oncology outlook, and GSK’s tech-specific self-sufficiency remains to be seen

Closing Opinion:

The Tesaro portfolio is proving useful for GSK, representing promise in the medium term. However, all assets report a subset-specific disease focus besides lacking synergies with established interventions.

GRG Health’s CI engagements have also revealed that there is a lack of adequate awareness and engagement even for proven assets like ZEJULA. This is concerning.

Further, GSK seems to lack a coherent strategy ever since the loss of its Respiratory assets – it would be worrying if an erstwhile, established leader in respiratory diseases relies more on M&A than either organic evolution or balanced development for the way forward.

The collective effect of such concerns is probably reflected in the consistently low share price of GSK.

In view of the above and the potential crowding of the PD-1/L1 space, GSK should aggressively focus on generating robust, broad-based data across indications to firmly establish its portfolio in oncology at the earliest.

[epigen-papers]

Genetic and epigenetic alterations in MGMT gene and correlation with concomitant chemoradiotherapy (CRT) in cervical cancer

Pubmed: http://dlvr.it/SvFtyG

[rnomics]

Data Normalization of Urine #miRNA Profiling from Head and Neck #cancer Patients Treated with Cisplatin

The #microRNA (#miRNA) expression profile by qRT-PCR depends directly on the most appropriate normalization strategy adopted; however, currently there is no universally adequate reference gene. Therefore, this study aimed to determine, considering #RNA-Seq results, the most adequate endogenous normalizer for use in the relative quantification of urine #miRNAs from head and neck #cancer patients, treated with cisplatin chemoradiotherapy. The massive sequencing was performed to identify the #miRNAs... https://pubmed.ncbi.nlm.nih.gov/37446060/?utm_source=dlvr.it&utm_medium=tumblr&utm_campaign=None&utm_content=1Zap-74u4XbiV7x0qz5lToBuxtoq00qwwHZUuXSRQOsim8UYds&fc=None&ff=20230718031523&v=2.17.9.post6%2086293ac

[sisiad]

Endoscopic resection for local residual or recurrent cancer after definitive chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma

http://dlvr.it/SrMPcq

[ptmasterguide]

Durvalumab (Clinical Trials Experience-4)

In this article, we will discuss Durvalumab (Clinical Trials Experience-4). So, let’s get started. The safety of Durvalumab in patients with Stage III NSCLC who completed concurrent platinum-based chemoradiotherapy within 42 days prior to initiation of study drug was evaluated in the PACIFIC study, a multicenter, randomized, double-blind, placebo-controlled study. A total of 475 patients…

[bigtreepeptide]

Peptide Powder Used For Tumor Prevention

Peptides effectively regulate the body's immune function, enhance the ability of immune surveillance, recognition, inhibition of cancerous cells in the body. Thymosin, albumin and nucleotide peptides in peptides can directly inhibit cancer cells. The peptide syntheses gamma globulin in human body, which can significantly improve the immune function of the body and reduce the symptoms of physical weakness and gastrointestinal reaction after radiotherapy and chemotherapy. Protein peptides are most effective for raising white blood cells in tumor (cancer) chemoradiotherapy populations. It can repair, activate and nourish growing cells. It can also synthesize cells and affect cell function and action. It stimulates the ability of the body's important immune cells, known as macrophages, to engulftumor (cancer) cells. Peptide through clinical nutrition support, enhance physical fitness, improve immunity

Epidemicity. Stimulates the ability of macrophages to engulf tumor cells, encouraging good cells to grow faster than cancer cells. Combined with radiotherapy and chemotherapy, the cancer cells will eventually be wiped out, so that cancer patients can survive.

Benefits of Peptide Powder Used For Tumor Prevention

Peptide refers to small molecule active peptide, which has an adjuvant therapeutic effect on tumors. Small molecule peptides can repair damaged cells and activate the immune system, enhancing the immune system's ability to recognize and kill cancer cells. In addition, if combined with radiotherapy and chemotherapy, it can improve the therapeutic effect and enhance the body's immunity.

Does Peptide Powder Helps With Cancer?

Small molecule active peptides that can help cancer patients greatly increase their chances of cure. For cancer patients after radiotherapy and chemotherapy, it can improve their quality of life and prolong their life cycle. Small molecule active peptides can inhibit the growth of tumor cells and prevent tumor cell metastasis after chemoradiotherapy: after entering the human body through the blood circulation, the peptides will combine with the polysaccharide of the human body and become oligosaccharides. The glycopeptides can cooperate with P-glucose, nucleoside and adenylate to continuously remove the "telomerase" released by cancer cells. Therefore, the peptides can stop cancer cells. Then it detaches from the tumor.

[gicancerindia]

 Anal Carcinoma

Understanding a Rare Cancer and its Management

Introduction:

Anal carcinoma is a relatively rare form of cancer that affects the anal canal, which is the last portion of the digestive tract. This type of cancer develops from the cells that line the anal canal and can have a significant impact on an individual's quality of life. In this article, we will explore the key aspects of anal carcinoma, including its causes, risk factors, symptoms, diagnostic methods, treatment options, and the importance of early detection.

Understanding Anal Carcinoma:

Anal carcinoma typically originates from the squamous cells that line the anal canal. While the exact cause of this cancer is not fully understood, it has been associated with certain risk factors such as infection with human papillomavirus (HPV), a weakened immune system, and a history of anal intercourse. Anal carcinoma can affect both men and women, although it is more commonly diagnosed in women.

Recognizing the Symptoms:

The symptoms of anal carcinoma can vary but often include persistent anal pain, itching, bleeding, discharge, changes in bowel habits, and the presence of a lump or mass near the anus. These symptoms can be similar to those of other benign conditions, which may delay diagnosis. It is important to seek medical attention if any concerning symptoms persist, as early detection can greatly impact treatment outcomes.

Diagnostic Methods:

Diagnosing anal carcinoma typically involves a combination of procedures and tests. A thorough physical examination, including a digital rectal examination, is performed to assess the anal canal and surrounding areas. Additional tests may include a biopsy, where a small tissue sample is taken for analysis, imaging studies such as MRI or CT scans to determine the extent of the cancer, and sometimes a specialized examination called an anoscopy, which uses a small tube with a light to visualize the anal canal more closely.

Treatment Options:

The treatment of anal carcinoma depends on various factors, including the stage of the cancer, the size and location of the tumor, and the overall health of the patient. The primary treatment modalities for anal carcinoma include a combination of chemotherapy and radiation therapy, often referred to as chemoradiotherapy. This approach aims to shrink the tumor and destroy cancer cells. In some cases, surgery may be recommended to remove the tumor, especially if it is large or has not responded adequately to initial treatment.

Supportive Care and Emotional Well-being:

Living with anal carcinoma can be emotionally challenging for both patients and their loved ones. Managing treatment side effects, coping with anxiety or depression, and adjusting to changes in body image and sexual function can be difficult. Supportive care services, including psychological counseling, support groups, and resources provided by healthcare professionals, can play a crucial role in addressing the emotional and psychological well-being of individuals affected by anal carcinoma.

Importance of Early Detection:

Early detection of anal carcinoma is vital for successful treatment outcomes. Regular screening for HPV, particularly for high-risk groups, can help identify precancerous changes in the anal canal and facilitate early intervention. Additionally, individuals should be aware of the potential risk factors and promptly seek medical attention if they experience persistent anal symptoms or notice any abnormalities in the anal area.

Conclusion:

Anal carcinoma is a relatively rare cancer that affects the anal canal, often associated with HPV infection and other risk factors. By increasing awareness, promoting regular screenings, and seeking timely medical care, we can improve the chances of early detection and successful treatment. A multidisciplinary approach that combines chemotherapy, radiation therapy, and surgical interventions, along with supportive care services, is crucial in managing anal carcinoma and supporting the well-being of affected individuals. With ongoing research and advances in treatment options, there is hope for improved outcomes and an enhanced quality of life for those facing anal carcinoma.

[sexualnews12]

Quality of Life and Sexual Function of Locally Advanced Cervical Cancer Survivors

Locally advanced cervical cancer (LACC) can be treated with chemoradiotherapy (CRT) or neoadjuvant chemotherapy (NACT) and radical hysterectomy (RH), and there is much debate about which treatment strategy is best for preserving individuals’ sexual functioning and quality of life. CRT has demonstrated drawbacks when it comes to cancer patients’ sexuality and quality of life, but less is known…

[mambasoftwares]

Treating Stage 2 Esophageal Cancer: A Comprehensive Approach

Introduction:

Esophageal cancer is a challenging disease, and its successful treatment relies on various factors, including the stage at diagnosis. Second stage (Stage 2) esophageal cancer indicates that the tumor has grown beyond the inner lining of the esophagus and potentially into nearby lymph nodes. While it presents significant challenges, there are various treatment options available to combat this condition. In this article, we will explore the comprehensive approach to curing Stage 2 esophageal cancer.

Accurate Diagnosis and Staging:

Accurate diagnosis and staging are crucial in determining the best treatment plan for Stage 2 esophageal cancer. Diagnostic procedures such as endoscopy, imaging tests (CT scan, PET scan), and biopsies help evaluate the extent of cancer spread. The staging process helps oncologists determine the most appropriate treatment approach.

Surgery:

Surgery plays a vital role in the treatment of Stage 2 esophageal cancer. Surgical options may include:

a) Esophagectomy: This procedure involves the removal of the affected portion of the esophagus and nearby lymph nodes. The remaining healthy portion of the esophagus is then reattached to the stomach or a portion of the large intestine.

b) Minimally invasive surgery: Techniques such as laparoscopic or robotic-assisted surgery may be used to reduce the invasiveness of the procedure, leading to shorter recovery times and fewer complications.

Radiation Therapy:

Radiation therapy uses high-energy X-rays or proton beams to target and destroy cancer cells. It may be used as a standalone treatment or in combination with surgery and/or chemotherapy. External beam radiation therapy and brachytherapy (internal radiation) are commonly employed to treat Stage 2 esophageal cancer.

Chemotherapy:

Chemotherapy involves the use of drugs to kill cancer cells throughout the body. It can be administered before surgery (neoadjuvant chemotherapy) to shrink tumors, after surgery (adjuvant chemotherapy) to eliminate any remaining cancer cells, or in combination with radiation therapy (chemoradiotherapy).

Targeted Therapy:

Targeted therapy utilizes drugs designed to target specific molecules or genetic abnormalities in cancer cells. This personalized approach aims to disrupt cancer cell growth and survival while minimizing harm to healthy cells. Targeted therapy options for esophageal cancer are continuously evolving and may be used in combination with other treatments.

Immunotherapy:

Immunotherapy helps boost the body’s immune system to recognize and attack cancer cells. Drugs like immune checkpoint inhibitors are designed to block proteins that inhibit the immune response, thereby enhancing the body’s ability to fight cancer. Clinical trials are exploring the efficacy of immunotherapy in treating esophageal cancer.

Supportive Care:

Treating Stage 2 esophageal cancer is physically and emotionally demanding. Supportive care plays a critical role in managing symptoms and improving the overall quality of life. This may include pain management, nutritional support, counseling, and palliative care to address physical and emotional needs.

Conclusion:

The treatment of Stage 2 esophageal cancer requires a comprehensive approach, involving a combination of surgery, radiation therapy, chemotherapy, targeted therapy, immunotherapy, and supportive care. The selection of treatment modalities depends on individual factors such as overall health, tumor location, and patient preferences. Collaborative decision-making between the medical team and the patient is crucial to developing an effective treatment plan. With advances in medical technology and ongoing research, the outlook for individuals diagnosed with Stage 2 esophageal cancer continues to improve, offering hope for a cure and a better quality of life.